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            UPDATE – Canadian Urological Association guideline: Male lower urinary tract symptoms/benign prostatic hyperplasia - PMC
        

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Can Urol Assoc J

. 2022 Apr 11;16(8):245–256. doi: [10.5489/cuaj.7906](https://doi.org/10.5489/cuaj.7906)

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#  _UPDATE_ – Canadian Urological Association guideline: Male lower urinary tract symptoms/benign prostatic hyperplasia

[Dean Elterman](https://pubmed.ncbi.nlm.nih.gov/?term=%22Elterman%20D%22%5BAuthor%5D)

### Dean Elterman

1Division of Urology, University of Toronto, Toronto, ON, Canada

Find articles by [Dean Elterman](https://pubmed.ncbi.nlm.nih.gov/?term=%22Elterman%20D%22%5BAuthor%5D)

1,✉, [Mélanie Aubé-Peterkin](https://pubmed.ncbi.nlm.nih.gov/?term=%22Aub%C3%A9-Peterkin%20M%22%5BAuthor%5D)

### Mélanie Aubé-Peterkin

2Division of Urology, McGill University, Montreal, QC, Canada

Find articles by [Mélanie Aubé-Peterkin](https://pubmed.ncbi.nlm.nih.gov/?term=%22Aub%C3%A9-Peterkin%20M%22%5BAuthor%5D)

2, [Howard Evans](https://pubmed.ncbi.nlm.nih.gov/?term=%22Evans%20H%22%5BAuthor%5D)

### Howard Evans

3Division of Urology, University of Alberta, Edmonton, AB, Canada

Find articles by [Howard Evans](https://pubmed.ncbi.nlm.nih.gov/?term=%22Evans%20H%22%5BAuthor%5D)

3, [Hazem Elmansy](https://pubmed.ncbi.nlm.nih.gov/?term=%22Elmansy%20H%22%5BAuthor%5D)

### Hazem Elmansy

4Division of Urology, Northern Ontario School of Medicine, Thunder Bay, ON, Canada

Find articles by [Hazem Elmansy](https://pubmed.ncbi.nlm.nih.gov/?term=%22Elmansy%20H%22%5BAuthor%5D)

4, [Malek Meskawi](https://pubmed.ncbi.nlm.nih.gov/?term=%22Meskawi%20M%22%5BAuthor%5D)

### Malek Meskawi

5Division of Urology, Université de Montréal, Montreal, QC, Canada

Find articles by [Malek Meskawi](https://pubmed.ncbi.nlm.nih.gov/?term=%22Meskawi%20M%22%5BAuthor%5D)

5, [Kevin C Zorn](https://pubmed.ncbi.nlm.nih.gov/?term=%22Zorn%20KC%22%5BAuthor%5D)

### Kevin C Zorn

5Division of Urology, Université de Montréal, Montreal, QC, Canada

Find articles by [Kevin C Zorn](https://pubmed.ncbi.nlm.nih.gov/?term=%22Zorn%20KC%22%5BAuthor%5D)

5, [Naeem Bhojani](https://pubmed.ncbi.nlm.nih.gov/?term=%22Bhojani%20N%22%5BAuthor%5D)

### Naeem Bhojani

5Division of Urology, Université de Montréal, Montreal, QC, Canada

Find articles by [Naeem Bhojani](https://pubmed.ncbi.nlm.nih.gov/?term=%22Bhojani%20N%22%5BAuthor%5D)

5

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1Division of Urology, University of Toronto, Toronto, ON, Canada

2Division of Urology, McGill University, Montreal, QC, Canada

3Division of Urology, University of Alberta, Edmonton, AB, Canada

4Division of Urology, Northern Ontario School of Medicine, Thunder Bay, ON, Canada

5Division of Urology, Université de Montréal, Montreal, QC, Canada

✉

Correspondence: Dr. Dean Elterman, Division of Urology, University of Toronto, Toronto, ON, Canada; Dean.Elterman@uhn.ca

✉

Corresponding author.

Issue date 2022 Aug.

Copyright: © 2022 Canadian Urological Association or its licensors

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PMCID: PMC9343161 PMID: [35905485](https://pubmed.ncbi.nlm.nih.gov/35905485/)

## Introduction

The current document summarizes the state-of-the-art knowledge as it relates to management of male lower urinary tract symptoms (MLUTS) secondary to benign prostatic hyperplasia (BPH) by updating the 2018 Canadian Urological Association (CUA) BPH guideline.1 The process continues to highlight the essential diagnostic and therapeutic information in a Canadian context. The information included in this document includes that reviewed for the 2010 guideline and further information obtained from an updated MEDLINE search of the Englishlanguage literature (search terms included BPH, alpha-blockers, 5-alpha reductase inhibitor, anti-cholinergic, beta3 agonist, phosphodiesterase type 5 inhibitor [PDE5I], transurethral resection of the prostate [TURP], monopolar, bipolar, open simple prostatectomy, enucleation, GreenLight, photoselective vaporization of the prostate [PVP], Aquablation, Rezum, UroLift, temporarily implanted nitinol device [iTiND]), as well as review of the most recent American Urological Association (AUA)2 and European Association of Urology (EAU) guidelines.3 References include those of historical importance, but management recommendations are based on literature published between 2000 and 2021. When information and data is available from multiple sources, the most relevant (usually most recent) article is cited based on committee opinion.

These guidelines are directed toward the typical male patient over 50 years of age presenting with LUTS and benign prostatic enlargement (BPE) and/or benign prostatic obstruction (BPO). It is recognized that men with LUTS associated with causes other than BPO may require more extensive diagnostic workup and different treatment considerations. We acknowledge that not all patients identify as male. These guidelines should also be applicable to non-binary people, transwomen, and any patients who may have anatomical features of a cis-male genitourinary tract, such as a prostate. It is our intent to make these guidelines inclusive to all persons experiencing LUTS or an enlarged prostate.

In this document, we will address both diagnostic and treatment issues. Diagnostic guidelines are described in the following terms as: mandatory, recommended, optional, or not recommended. The recommendations for diagnostic guidelines and principles of treatment were developed on the basis of clinical principle (widely agreed upon by Canadian urologists) and/or expert opinion (consensus of committee and reviewers). The grade of recommendation will not be offered for diagnostic recommendations. Guidelines for treatment are described using the GRADE approach4 for summarizing the evidence and making recommendations.

## 1\. Diagnostic guidelines

The committee recommended minor revisions in regard to diagnostic considerations as outlined in the 2018 CUA BPH guideline.1

### 1.1. Mandatory

Mandatory evaluations include:

  * – History

  * – Physical examination, including DRE

  * – Urinalysis




In the initial evaluation of a man presenting with LUTS, the evaluation of symptom severity and bother is essential. Medical history should include relevant prior and current illnesses, as well as prior surgery and trauma. Current medication, including over-the-counter drugs and phytotherapeutic agents, must be reviewed. A focused physical examination, including a digital rectal exam (DRE), is also mandatory. Urinalysis is required to rule out diagnoses other than BPH that may cause LUTS and may require additional diagnostic tests.1–3,5–7

### 1.2. Recommended

#### Symptom inventory (should include bother assessment)

A formal symptom inventory (e.g., International Prostate Symptom Score [IPSS] or AUA Symptom Index [AUA-SI]) is recommended for an objective assessment of symptoms at initial consultation, for followup of symptom evolution for those on watchful waiting, and for evaluation of response to treatment.8–11

#### Prostate-specific antigen

Testing of prostate-specific antigen (PSA) should be offered to patients who have at least a 10-year life expectancy and for whom knowledge of the presence of prostate cancer would change management, as well as those for whom PSA measurement may change the management of their voiding symptoms (i.e., estimate for prostate volume that may lead to more precise measurements). Among patients without prostate cancer, serum PSA may also be a useful surrogate marker of prostate size and may also predict risk of BPH progression.12,13

### 1.3. Optional

In cases where the physician feels diagnostic uncertainty exists, it is reasonable to proceed with one or more of the following:

  * – Serum creatinine

  * – Urine cytology

  * – Uroflowmetry

  * – Postvoid residual (PVR)

  * – Voiding diary (recommend frequency volume chart for men with suspected nocturnal polyuria)

  * – Obstructive sleep apnea (OSA) screening for men with nocturia over the age of 50 (STOP BANG questionnaire)

  * – Sexual function questionnaire




### 1.4. Not recommended

The following diagnostic modalities are not recommended in the routine initial evaluation of a typical patient with BPH-associated LUTS. **These investigations may be required** in patients with another indication, such as hematuria, diagnostic uncertainty, DRE abnormalities, poor response to medical therapy, or for surgical planning:

  * – Cytology

  * – Cystoscopy

  * – Urodynamics

  * – Radiological evaluation of upper urinary tract

  * – Prostate ultrasound

  * – Prostate biopsy




An algorithm summarizing the appropriate diagnostic steps in the workup of a typical patient with MLUTS/BPH is summarized in Figure 1.

#### Figure 1.

![Figure 1](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6119/9343161/9993baf253fa/CUAJ-8-g246-01.jpg)

[Open in a new tab](figure/f1-cuaj-8-245/)

Algorithm of appropriate diagnostic steps in the workup of a typical patient with male lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). PE: physical exam; PSA: prostate-specific antigen; PVR: postvoid residual; U/A: urinalysis.

### 1.5. Further diagnostic considerations for surgery

#### Indications for surgery

Indications for MLUTS/BPH surgery1–3 include 1) recurrent or refractory urinary retention; 2) recurrent urinary tract infections (UTIs); 3) bladder stones; 4) recurrent hematuria; 5) renal dysfunction secondary to BPH; 6) symptom deterioration despite medical therapy; and 7) patient preference. The presence of a bladder diverticulum is not an absolute indication for surgery unless associated with recurrent UTI or progressive bladder dysfunction.

#### Preoperative testing

Determination of prostate size and extent of median lobe are related to procedure-specific indications (see section on _Surgical Treatment_). For patients in whom surgery is being considered, cystoscopy should be performed to evaluate prostate size, as well as presence or absence of significant middle/median lobe and/or bladder calculi. Ultrasound (US) (either by transrectal ultrasound [TRUS] or transabdominal US) is recommended to determine the volume of the prostate and the extent of median lobe presence in order to select appropriate modality of surgical therapy. This information can also be obtained from a recent abdominal computed tomography (CT) or magnetic resonance imaging (MRI).

## 2\. Treatment guidelines

### 2.1 Principles of treatment

Therapeutic decision-making should be guided by the severity of the symptoms, the degree of bother, and patient preference. Information on the risks and benefits of BPH treatment options should be explained to all patients who are bothered enough to consider therapy. Patients should be invited to participate as much as possible using a shared decisionmaking approach to determine the best treatment selection for them. This can be facilitated with the use of the CUA surgical BPH decision aid.14 The patient’s therapeutic goal of management should be discussed and documented.

Patients with mild symptoms (e.g., IPSS <7) should be counselled about a combination of lifestyle modification and watchful waiting. Patients with mild symptoms and severe bother should undergo further assessment.

Treatment options for patients with bothersome moderate (e.g., IPSS 8–18) and severe (e.g., IPSS 19–35) symptoms of BPH include watchful waiting/lifestyle modification, as well as medical, minimally invasive, or surgical therapies.

Physicians should use baseline age, LUTS severity, and prostate volume to advise patients of their individual risk of symptom progression, acute urinary retention (AUR) or future need for BPH-related surgery (these risk factors identify patients at risk for progression).

A variety of lifestyle changes may be suggested for patients with non-bothersome symptoms. These can include:

  * – Fluid restriction, particularly prior to bedtime

  * – Avoidance of caffeinated beverages, alcohol, and spicy foods

  * – Avoidance/monitoring of some drugs (e.g., diuretics, decongestants, antihistamines, antidepressants)

  * – Timed or organized voiding (bladder retraining)

  * – Avoidance or treatment of constipation

  * – Weight loss and prevention or treatment of conditions associated with metabolic syndrome

  * – Pelvic floor physical therapy (PFPT) in cases of suspected non-relaxing pelvic floor dysfunction (causing LUTS, pelvic and or genital pain, bowel and sexual dysfunction, etc.) or overactive bladder and/or urinary incontinence (Kegel exercises, urge suppression, etc.)




### 2.2. Post-treatment followup

#### Watchful waiting

Patients on watchful waiting should have periodic physicianmonitored visits to monitor for any complications associated with their BPO. Physicians should assess either progression of bother, i.e., validated questionnaire such as IPSS (subjective) or worsening urinary function, i.e., uroflowmetry or PVR (objective).

#### Medical therapy

Patients started on medical therapy should have followup visit(s) to assess for efficacy and safety (side effects) of medications. If the patient-directed therapeutic goal is achieved, the patient may be followed by the primary care physician as part of a shared-care approach. The primary care physician should be counselled with clear instructions on followup and re-referral as necessary.

#### Surgical therapy

Patients who receive prostate surgery for BPH should be reviewed 4–6 weeks after catheter removal to evaluate treatment response (with symptom assessment [e.g., IPSS], and if indicated, uroflowmetry and PVR volume). Side effects and adverse events should also be screened for. The individual patient’s circumstances and type of surgical procedure employed will determine the need for and type of further followup required by the urologist and/or primary care physician.

### 2.3 Medical therapy

The committee recommended few changes in the recommendations for the primary medical management of BPH and MLUTS with alpha-blockers and/or 5-alpha-reductase inhibitors (5ARIs) since 2018. Since the 2018 guideline publication, new evidence is available in regard to other medical therapy, namely beta-3 agonists, for the treatment of MLUTS.

#### 2.3.1. Alpha-blockers

Alfuzosin, doxazosin, tamsulosin, terazosin, and silodosin are appropriate treatment options for LUTS secondary to BPH.12–23 Doxazosin and terazosin require dose titration and blood pressure monitoring. Alpha-blockers do not alter the natural progression of BPH (little impact on prostate growth, risk of urinary retention, or the need for BPH-related surgery). The most common adverse effect associated with alpha-blockers is dizziness (2–10%, with the highest rates for terazosin and doxazosin), while ejaculatory disturbances are most often reported with tamsulosin and silodosin. Floppy iris syndrome has been reported in patients on alpha-blockers, particularly tamsulosin, but this does not appear to be an issue in men with no planned cataract surgery and can be managed by the ophthalmologist, who is aware that the patient is on the medication.24Although there are differences in the adverse event profiles of these agents, all five agents appear to have equal clinical effectiveness. The choice of agent should depend on the patient’s comorbidities, side effect profile, and tolerance.

**We recommend alpha-blockers as an excellent first-line therapeutic option for men with symptomatic bother due to BPH who desire treatment** _(strong recommendation, evidence level A)_.

#### 2.3.2. 5-ARIs

Several studies have demonstrated that 5-ARI therapy, in addition to improving symptoms and causing a modest (25–30%) shrinkage of the prostate, can alter the natural history of BPH through a reduction in the risk of AUR and the need for surgical intervention.25,26 Efficacy is noted in patients with a prostate volume >30 cc (and/or PSA levels >1.5 ng/ml). 5-ARI treatment is associated with erectile dysfunction, decreased libido, ejaculation disorders, and rarely, gynecomastia and post-finasteride syndrome.27

**We recommend 5-ARIs (dutasteride and finasteride) as appropriate and effective treatment for patients with LUTS associated with demonstrable prostatic enlargement** _(strong recommendation, evidence level A)_.

#### 2.3.3. Combination therapy (alpha-blocker and 5-ARI)

Prognostic factors suggesting the potential for BPH progression risk28,29 include: serum PSA >1.4 ng/mL, age >50 years, and gland volume >30 cc. Clinical trial results have shown that combination therapy significantly improves symptom score and peak urinary flow compared with either of the monotherapy options. Combination medical therapy is associated with decreased risk of urinary retention and/or prostate surgery, but also the additive side effects of dual therapy (in particular, ejaculatory disturbances).30,31

**We recommend the combination of an alpha-adrenergic receptor blocker and a 5-ARI as an appropriate and effective treatment strategy for patients with symptomatic LUTS associated with prostatic enlargement ( >30 cc)** _(strong recommendation, evidence level B)_.

It may be appropriate to consider discontinuing the alphablockers in patients successfully managed with combination therapy after 6–9 months of combination therapy.32,33

**We suggest that patients successfully treated with combination therapy may be given the option of discontinuing the alpha-blocker. If symptoms recur, the alpha-blocker should be restarted** _(conditional recommendation, evidence level B)_.

#### 2.3.4. Antimuscarinic and beta-3 agonist medications

Storage symptoms (urgency, frequency, nocturia) are a bothersome component of MLUTS associated with BPH. Antimuscarinics (anticholinergics) and the beta-3 agonists have demonstrated improvements in male storage LUTS (with and without BPH), including reductions in frequency, urgency, and urgency incontinence episodes.34,35 Studies of contemporary antimuscarinics, such as tolterodine and fesoterodine, and the beta-3 agonist, mirabegron, have shown low rates of urinary retention, although caution should be exercised in elderly men and those with significant bladder outlet obstruction (BOO) (with PVR >250–300 cc since there is little evidence of safety in men with high PVRs).

**We suggest that antimuscarinics or beta-3 agonists may be useful in predominately storage symptoms and BPH, and used with caution in those with significant BOO and/or an elevated PVR** _(conditional recommendation, evidence level C)_.

#### 2.3.5. Antimuscarinic or beta-3 agonists in combination with alpha-blockers

Mixed LUTS (storage and voiding symptoms) can be managed safely with alpha-blockers in combination with antimuscarinics or beta-3-agonists. Clinical trials studied the following drug combinations: tamsulosin 0.4 mg plus solifenacin 5 mg, tamsulosin plus tolterodine ER 4 mg, and tamsulosin 0.4 mg plus mirabegron 50 mg.36–41 Evidence showed that combination therapies provide significant improvement in storage symptoms without clinical or statistical evidence of decreased maximum flow rate on uroflowmetry (Qmax) or increased risk of retention. Patients with high PVR >200 ml or previous history of AUR were excluded.

**We suggest that an alpha-blocker combined with an antimuscarinic or beta-3 agonist may be useful to treat LUTS/BPH in men with both voiding and storage symptoms and failure of alpha-blocker monotherapy** _(conditional recommendation, evidence level B)_.

#### 2.3.6. Phosphodiesterase inhibitors

PDE5Is have been shown to not only improve erectile function, but also are an effective treatment for male LUTS. Tadalafil 5 mg daily, due to its longer half-life, is approved for MLUTS. Studies have shown improvements in IPSS, storage and voiding symptoms, and quality of life.42 Evidence shows that combination therapy with PDE5I and alpha-blockers is superior to alpha-blockers alone in men with voiding symptoms and erectile dysfunction.43

**We recommend long-acting PDE5Is as monotherapy for men with LUTS/BPH, particularly in men with both LUTS and erectile dysfunction** _(strong recommendation, evidence level B)_.

#### 2.3.7. Desmopressin

Nocturnal polyuria (NP) often coexists with MLUTS and BPH but may not respond to typical BPH pharmacotherapies. NP is a major contributing factor of nocturia and is defined by the International Continence Society (ICS) as an abnormally large volume of urine during sleep. More specifically, 33% of the total daily urine volume occurs at night, while the daily total urine output remains normal. Desmopressin is a synthetic analogue of the antidiuretic hormone, arginine vasopressin (AVP). Desmopressin reduces total nocturnal voids and increases hours of undisturbed sleep by reducing urine production in men with NP.44 While the risk of hyponatremia is low in men with normal baseline serum sodium, sodium must be checked at baseline in all men, as well as 4–8 days and 30 days after initiation of treatment in men taking desmopressin melts or men ≥65 years taking 50 μg oral disintegrating tablet. In men whose predominant symptom is bothersome nocturia and who do not respond to conservative measures or other monotherapies, desmopressin should be considered.

**We recommend desmopressin as a therapeutic option in men with LUTS/BPH with nocturia as result of NP** _(conditional recommendation, evidence level B)_.

#### 2.3.8. Phytotherapies

Plant-based herbal preparations may appeal to some patients. Common formulations include Serenoa repens (saw palmetto), Pygeum africanum (African plum bark), and Urtica dioica (stinging nettle). Phytotherapies lack consistent formulation, predictable pharmacokinetics, and regulatory oversight. Numerous studies and Cochrane meta-analyses report no significant difference between phytotherapies and placebo, as measured by AUA-SI, peak flow rates, prostate volume, residual urine volume, PSA, or quality of life.45–48 There are few side effects associated with phytotherapies but there are important potential drug interactions.

**We do not recommend phytotherapies as standard treatment for MLUTS/BPH** _(strong recommendation, evidence level B)_.

### 2.4. Surgical therapy

#### 2.4.1. TURP

##### Monopolar TURP

Monopolar TURP (M-TURP) remains the primary, standard-reference surgical treatment option for moderate-to-severe LUTS due to BPH in patients with prostate volume 30–80 cc.49 Perioperative mortality has decreased over time and is currently approximately 0.1%, while morbidity is related to prostate volume (particularly >60 cc).50 Contemporary series have reported the following complications: bleeding (2–9%), capsule perforation with significant extravasation (2%), TUR syndrome (0.8%), urinary retention (4.5–13%), infection (3–4%; sepsis 1.5%), incontinence (<1%), bladder neck contracture (3–5%), retrograde ejaculation (65%), erectile dysfunction (6.5%), and need for surgical retreatment (2%/year).51,52

**We recommend M-TURP as a standard first-line surgical therapy for men with moderate-to-severe LUTS/BPH with prostate volume of 30–80 cc** _(strong recommendation, evidence level A)_.

##### Bipolar TURP (including bipolar plasma kinetic vaporization)

Bipolar TURP (B-TURP) offers a resection alternative to M-TURP in men with moderate to-severe LUTS secondary to BPH with similar efficacy, but lower perioperative morbidity.52–54 The predominant difference between M-TURP and B-TURP is the decreased risk of perioperative bleeding and TUR syndrome. The choice of B-TURP should be based on equipment availability, surgeon experience, and patient preference.

**We recommend B-TURP as a standard first-line surgical therapy for men with moderate-to-severe LUTS/BPS with prostate volume of 30–80 cc** _(strong recommendation, evidence level B)_.

#### 2.4.2. Open simple prostatectomy

Open simple prostatectomy (OSP) is an effective treatment alternative for men with moderate-to-severe LUTS with substantially enlarged prostates >80 cc and who are significantly bothered by symptoms.55 Other indications for OSP include plans for concurrent bladder procedure, such as diverticulectomy or cystolithotomy (for very large bladder calculi) and in men who are unable to be placed in dorsal lithotomy position due to severe hip disease.56 OSP is the most invasive surgical method requiring longer hospitalization and catheterization. The estimated transfusion rate has been reported as 7–14%.55,56 Complications include transient urinary incontinence (8–10%), bladder neck contracture, and urethral stricture (5–6%).55,56

**We recommend OSP as a first-line surgical therapy when anatomic endoscopic enucleation of the prostate (AEEP) (see below) is unavailable for men with moderate-to-severe LUTS/BPS and enlarged prostate volume >80 cc** _(strong recommendation, evidence level A)_.

#### 2.4.3. Minimally invasive simple prostatectomy

With the advent of minimally invasive surgery, starting with laparoscopy and proceeding to robotic-assisted laparoscopy, the natural evolution came to the OSP as well. These techniques are still relatively new.

Laparoscopic simple prostatectomy (LSP) and robot-assisted simple prostatectomy (RASP), like OSP, are indicated in patients with significantly enlarged prostates (>80–100cc) and bothersome LUTS.57,58 They are also beneficial when performed due to concomitant pathology, such as large bladder stones or bladder diverticulum. There are no randomized controlled trials comparing LSP and RASP to OSP or to any other enucleation procedure. The largest retrospective series includes both techniques and has shown both to be safe and effective.59 A recent systematic review found that RASP showed similar improvements in IPSS, PVR, Qmax, and quality of life, while having similar complication rates and estimated blood loss (EBL) to laser vaporization and enucleation of the prostate.60 In comparison to OSP, the length of stay (LOS) and EBL are significantly lower for RASP.61 Finally, catheterization time and LOS are longer with RASP compared to laser enucleation of the prostate.60

**We recommend LSP or RASP as alternative surgical therapies for men with moderate-to-severe LUTS/BPS and enlarged prostate volume >80 cc in centers where there are surgeons with high-level expertise in robotics or laparoscopy** (_conditional recommendation, evidence level B_).

#### 2.4.4. AEEP

AEEP adopts the principle of open prostatectomy (OP) using different energy sources and instruments. The holmium laser (HoLEP) with or without Moses technology, GreenLight laser (GreenLEP), monopolar enucleation (MonolEP), bipolar enucleation (BipolEP), diode laser (DiLEP), thulium laser (ThuLEP), and thulium fiber laser (ThuFLEP) are among the available energy sources. The efficacy and safety of AEEP, regardless of the energy source used, have been widely demonstrated.62

When compared to TURP and OSP, AEEP was associated with greater improvements in IPSS, Qmax, and PVR. AEEP resulted in greater prostate tissue removal, reduced hemoglobin loss, shorter catheterization time, and shorter LOS.63

Recent evidence supports the use of AEEP in patients with BPH on anticoagulant (AC) or antiplatelet (AP) therapy.64–66 AEEP has demonstrated durable results, with a low reoperation rate of 0–3.7% (attributed to adenoma regrowth) on long-term followup of up to 18 years.67–71 The procedure requires a steep learning curve (estimated >20–50 cases).72

**We recommend AEEP as an alternative to TURP or OSP in men with moderate-to-severe LUTS and any size prostate >30 cc if performed by an AEEP-trained surgeon. AEEP can be safely performed in patients on AC/AP therapy** _(strong recommendation, evidence level A)_.

#### 2.4.5. PVP

GreenLight-PVP (180W XPS and 120W HPS systems) provides comparable outcomes to TURP in terms of durable improvements in IPSS and Qmax, with similar overall complication rate.73 Five-year mid-term durability of XPS reported a 1.1% retreatment rate in prostates with volumes of an average 80 g.74 In the GOLIATH international, multicenter, randomized controlled trial comparing the 180W XPS PVP to TURP for prostate volumes 30–80cc, there was a statistically significant difference in early adverse events, notably bleeding-related one, within the first 30 days favoring XPS PVP.68,75 Compared to TURP, PVP has better perioperative safety, shorter catheterization time, and shorter hospitalization.76 Multiple studies have demonstrated that PVP is safe and effective for elderly men, with significant medical comorbidities,77 large median lobes,78 and in patients who continue their AC/AP therapy, with negligible transfusion rates.79–81 Further to GreenLight safety profile, PVP has been shown to be a cost-effective alternative to TURP in the Canadian setting.82 There exists no size or shape limitation to PVP; only surgeon expertise and clinical judgement dictate size limitations.

**We recommend PVP as an alternative to M-TURP or B-TURP in men with moderate-to-severe LUTS** _(strong recommendation based on high-quality evidence)_. **We also suggest GreenLight PVP therapy as an alternate surgical approach in men on anticoagulation or with a high cardiovascular risk** _(conditional recommendation, evidence level B)_.

#### 2.4.6. Transurethral incision of the prostate

Transurethral incision of the prostate (TUIP) is an appropriate therapy for men with a small prostate size <30 cc without a middle lobe.83 Symptoms and voiding parameters are improved and the risk of retrograde ejaculation and TUR syndrome is reduced (18.2% and 0%, respectively) compared to TURP; however, the risk of surgical retreatment for LUTS related to BPH are significantly higher for TUIP (18.4%) than after TURP (7.2%).

**We recommend TUIP to treat moderate-to-severe LUTS in men with prostate volume <30 cc without a middle lobe. Patients should be made aware of the high retreatment rate** _(strong recommendation, evidence level B)_.

#### 2.4.7. Minimally invasive techniques

##### Transurethral microwave therapy

Transurethral microwave therapy (TUMT) is an option for elderly patients with significant comorbidities or greater anesthesia risks, as this procedure can be performed under local ansthesia.84,85 Although short-term success for LUTS improvement has been reported, the long-term durability of TUMT is limited, with five-year cumulative retreatment rates from 42–59%.86 TUMT should not be performed in patients with a significant median lobe.

**We suggest TUMT therapy as a consideration for treatment of carefully selected, well-informed men** _(conditional recommendation, evidence level C)_.

##### Prostatic stents

Temporary stents can provide short-term relief from BPO in patients temporarily unfit for surgery.87 In general, stents are subject to misplacement, migration, and poor tolerability because of exacerbation of LUTS and encrustation. Given these common side effects, prostatic stents have a limited role in the treatment of moderate-to-severe LUTS. A newer generation of stents are currently being evaluated and may provide an alternative surgical option for the management of BPH/LUTS in the future.

**We suggest prostatic stents only as an alternative to catheterization in men unfit for surgery with a functional detrusor** _(conditional recommendation, evidence level C)_.

##### Prostatic urethral lift

The prostatic urethral lift procedure, or UroLift®, (small, permanent, suture-based nitinol tabbed implants compress encroaching lateral lobes delivered under cystoscopic guidance), provides less effective but adequate and durable improvements in IPSS and QMax compared to TURP while preserving sexual function (no reported retrograde ejaculation observed at 12 months).88 Most complications are mild and resolve within four weeks but include dysuria (34%), hematuria (26%), pelvic pain (19%), urge incontinence (7%), and UTI (3%). Surgical retreatment was 13.6% over five years.89 A recent study (MedLift study) reported on the use of prostatic urethral lift in patients with a median lobe. For middle lobe deployment, the intravesical tissue is pulled into the prostatic fossa and affixed to either side of the urethra. Fort-four patients underwent this technique and results are very similar to the pivotal L.I.F.T. trial regarding improved IPSS and IPSS quality of life, while preserving ejaculatory function. It should be noted that followup for this study was only 12 months.90

**We suggest that prostatic urethral lift (UroLift) may be considered as an alternative treatment for men with LUTS interested in preserving ejaculatory function with prostates <80 cc. Prostatic urethral lift can also be be offered to patients with a small-to-moderate median lobe and bothersome LUTS. Patients (with or without a median lobe) should be made aware of the higher retreatment rate at five years** _(conditional recommendation, evidence level C)_.

##### Convective water vapor energy ablation

Ablations using the Rezum® system (uses the thermodynamic principle of convective energy transfer) report significant improvement of IPSS and Qmax at three months and sustained until 12 months,91 with preservation of erectile and ejaculatory function.92 Recent five-year results have confirmed durability of the positive clinical outcomes, with a 57% reduction in IPSS, 45% increase in quality of life, and 44% increase in Qmax. Surgical retreatment rate is 4.4% at five years.93

**We suggest that the Rezum system of convective water vapor energy ablation may be considered an alternative treatment for men with LUTS interested in preserving ejaculatory function with prostates <80 cc, including those with a median lobe** _(conditional recommendation, evidence level C)_.

##### Image-guided robotic waterjet ablation

Aquablation (robotic-guided hydrodissection ablates prostatic parenchyma while sparing collagenous structures such as blood vessels and the surgical capsule)94 has shown comparable improvements in efficacy and safety compared to TURP in men with <80 cc prostates.95 Additional studies have also demonstrated efficacy and safety in glands 80–150 cc. Aquablation preserves erectile and ejaculatory function in nearly 100% and approximately 90% of patients, respectively. Five-year retreatment rates are low (6% at five years).

**We suggest that Aquablation be offered to men with LUTS interested in preserving ejaculatory function with prostates <150 cc, with or without a middle lobe** _(conditional recommendation, evidence level C)_.

##### Temporary implantable nitinol device

Temporary implantable nitinol device (iTind) is a temporary (five days and then removed under local anesthetic), mechanical, stent-like device designed to remodel the bladder neck and the prostatic urethra through pressure necrosis.

Three prospective, randomized clinical trials (n=269) have demonstrated IPSS reduction of 45–60%, Qmax increase of 50–110%, no changes in erectile or ejaculatory function, and a retreatment rate of 9% at three years.96–98 Long-term durability studies are pending.

**We recommend that iTind may be offered to men with LUTS interested in preserving ejaculatory function, with prostates 30–80 cc. Patients should be made aware of the higher retreatment rate at 3 years** _(conditional recommendation, evidence level C)_.

##### Prostatic artery embolization

Prostatic artery embolization (PAE) is a minimally invasive treatment option exclusively performed by interventional radiologists at specialized centers. PAE results in significant IPSS, Qmax, and PVR improvement compared to baseline at 12 months,99 however, inferior outcomes compared to TURP100–102 or OSP.103 Although PAE has reportedly fewer complications than TURP, non-targeted embolization may lead to rare ischemic complications like transient ischemic proctitis, bladder ischemia, urethral and ureteral stricture, or seminal vesicles ischemia.104 Efficacy of PAE may be more advantageous in prostate volumes >80 mL,105 and can be considered as a treatment for gross hematuria of prostatic origin.106

**At centers with urological and radiological collaboration and technical expertise, highly selected, well-informed patients may be offered PAE if they wish to consider an alternative treatment option. Patients should be informed of lack of long-term durability** _(conditional recommendation, evidence level C)_.

Algorithms summarizing the management of a patient with MLUTS/BPH are summarized in Figures 2, 3.

###### Figure 2.

[![Figure 2](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6119/9343161/b1a87ea26784/CUAJ-8-g252-01.jpg)](https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=9343161_CUAJ-8-g252-01.jpg)

[Open in a new tab](figure/f2-cuaj-8-245/)

Male lower urinary tract symptoms/benign prostatic hyperplasia (MLUTS/BPH) management algorithm. ED: erectile dysfunction; PDE5: phosphodiesterase type 5; PSA: prostate-specific antigen.

###### Figure 3.

[![Figure 3](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6119/9343161/873efbce2a6d/CUAJ-8-g253-01.jpg)](https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=9343161_CUAJ-8-g253-01.jpg)

[Open in a new tab](figure/f3-cuaj-8-245/)

Treatment algorithm of bothersome lower urinary tract symptoms (LUTS) refractory to conservative/medical treatment or in cases of absolute operation indications. The flowchart was stratified by the patient’s ability to have anesthesia, cardiovascular risk, and prostate volume. *Current standard/first choice. The alternative treatments are presented in alphabetical order. **Must exclude the presence of a middle lobe. BPH: benign prostatic hyperplasia; B-TURP: bipolar transurethral resection of the prostate; HoLEP: holmium laser enucleation of the prostate; iTIND: temporary implantable nitinol device; M/TURP: monopolar transurethral resection of the prostate; PVP: photoselective vaporization of the prostate; TUIP: transurethral incision of the prostate; TUMT: transurethral microwave therapy.

### 2.5. Special situations

#### AUR

Data suggest that in patients with AUR, the use of alpha-blockers (specifically tamsulosin, alfuzosin, and silodosin) during the period of catheterization will increase the chances of successful voiding after catheter removal,107,108 while the addition of a 5-ARI may decrease the risk of future prostate surgery.30,31,109

**We suggest that men with AUR secondary to BPH may be offered alpha-blocker therapy during the period of catheterization** _(conditional recommendation, evidence level B)_.

#### Detrusor underactivity

There is no effective treatment for detrusor underactivity (DU), defined as a contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or a failure to achieve complete bladder emptying within a normal time span.110 In primary DU, treatment approach should be to facilitate bladder emptying, identify agents that can decrease bladder contractility, or increase urethral resistance. Behavioral modification, including scheduled voiding and or double voiding, clean intermittent self-catheterization (CIC), or indwelling catheters, are optional strategies.111 The data suggests that DU is not necessarily a contraindication for TURP or enucleation.112,113

**We have no evidence-based specific recommendation for management of DU**.

#### BPH-related bleeding

A complete assessment, including history and physical examination, urinalysis (routine microscopy, culture and sensitivity, cytology), upper tract radiological assessment, and cystoscopy, is necessary to exclude other sources of bleeding. Finasteride has been reported to reduce the risk of recurrent BPH-related hematuria.114

**We suggest that a trial with a 5-ARI is appropriate in men with BPH-related hematuria** (_conditional recommendation, evidence level C)_.

#### BPH patients with prostate cancer concern

The BPH patient with an elevated serum PSA and negative prostate biopsy may be counselled on the potential benefits of 5-ARI therapy (finasteride, dutasteride) for prostate cancer detection risk reduction.115,116 The patient must be aware of the possible low absolute increased risk (0.5–0.7%) in incidence of high-grade (Gleason 8–10) cancer with 5-ARI use. Most experts believe this phenomenon was observed due to an artifact of prostate glandular cytoreduction, induced by the 5-ARI, and it appears there is no demonstrable increase in prostate cancer mortality.117 Patients on 5-ARI therapy who experience a rising PSA 6–12 months after PSA nadir is reached should be assessed for the possibility of high-grade prostate cancer.118

**We recommend case-to-case, patient-specific informed discussion and close PSA followup, as indicated, in men on 5-ARI therapy treatment for BPH** _(conditional recommendation, evidence level B)_.

## Summary

MLUTS secondary to BPH remains one of the most common age-related disorders afflicting men. As the aging of the Canadian population continues, more men will be seeking advice and looking for guidance from their healthcare providers on the management of their symptoms. The information offered in this guideline document, based on consensus evaluation of the best available evidence, will aid Canadian urologists as they strive to provide state-of-the-art care to their patients.

## Footnotes

Prior to publication, this guideline update was reviewed by the CUA Guidelines Committee and the CUA Board of Directors.

**Competing interests:** Dr. Elterman has attended advisory boards for, is a speaker for, and has received grant funding from Allergan, Astellas, Boston Scientific, Ferring, Medtronic, and Pfizer; and has participated in clinical trials supported by Astellas, Medtronic, Meditate, and Procept Biorobotics. Dr. Aubé-Peterkin is an investigator for the Optilume trial supported by Urotronic. Dr. Elmansy has received honoraria from Boston Scientific, Lumenis, and Clarion Medical Technologies. Dr. Zorn has received honoraria from Boston Scientific and as a proctor/lecturer for Greenlight; and participated in the WATER 2 supported by Procept Biorobotics. Dr. Bhojani is a consultant for Boston Scientific, Olympus, and Procept BioRobotics; and has participated in the WATER 2 trial supported by Procept BioRobotics. The remaining authors do not report any competing personal or financial interests related to this work

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title: Guidelines for the Treatment of Benign Prostatic Hyperplasia
scrape_date: 2025-02-28T17:23:19.115920
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Published August 18, 2016

[UROLOGY/NEPHROLOGY](/topic/urology-nephrology)

# Guidelines for the Treatment of Benign Prostatic Hyperplasia

**Yunuo Wu, PharmD** _  
Community Practice Resident  
Creighton University School of Pharmacy and Health Professions_

**Michael H. Davidian, MD, MS** _  
Associate Professor of Medicine  
Creighton University School of Medicine_

**Edward M. DeSimone II, RPh, PhD, FAPhA** _  
Professor of Pharmacy Sciences  
Creighton University School of Pharmacy and Health Professions_ _  
Omaha, Nebraska_

_US Pharm_. 2016;41(8):36-40. 

**ABSTRACT:** _Benign prostatic hyperplasia (BPH) is a common disorder in men with an incidence that increases with age. BPH often requires therapy when patients begin to experience lower urinary tract symptoms that affect quality of life. Current management strategies involve lifestyle modifications, pharmacotherapy, phytotherapy, and surgical interventions as indicated. Pharmacists are in the unique position of being accessible sources of healthcare information for the BPH patient population. Understanding the symptoms of this disorder and therapy options will be beneficial for pharmacists who have increased chances to answer BPH-related questions from their patients._

Benign prostatic hyperplasia (BPH) is a common disorder that presents in men and increases in incidence with age. It is characterized by the nonmalignant growth of the prostate gland that occurs in most men >40 years of age. The prevalence of BPH, as seen in several autopsy studies around the world, is estimated to be approximately 20% for men in their 40s, up to 60% for men in their 60s, and up to 90% for men in their 70s and 80s.1 Although almost all men will develop histologic or microscopic evidence of BPH by their eighth decade of life, the condition does not require treatment until it becomes symptomatic.

## **PATHOPHYSIOLOGY**

Prostatic enlargement with increased age is correlated with smooth muscle hyperplasia and may eventually lead to bladder outlet obstruction (BOO).2 The most common presentation of subjective BPH-associated symptoms is lower urinary tract symptoms (LUTS).3 LUTS may further be classified into obstructive and irritative symptoms. Examples of obstructive symptoms include urine hesitancy, straining, weak flow, prolonged voiding, partial or complete urinary retention, and urinary incontinence. Common irritative symptoms include urinary frequency, urgency, nocturia, dysuria, and decreased void volume.1

## **DIAGNOSIS**

Diagnosis of BPH often rules out other clinical manifestations that may present with similar symptoms. Examples include prostate cancer, prostatitis, bladder cancer, bladder stones, overactive bladder (OAB), interstitial cystitis, and urinary tract infections; all of which may also cause LUTS.3 Although symptoms related to BPH are often not life-threatening, they can be debilitating and affect quality of life (QOL) significantly. Thus, it is important to identify and correctly diagnose BPH in order to pursue an effective treatment strategy.

The American Urological Association (AUA) guideline panel made several recommendations for the diagnosis of BPH that were consistent with an article published by Abrams et al in 2009.2,4 The recommendations state that a basic evaluation should be performed on patients who are experiencing negative changes in their QOL due to LUTS. This evaluation may include several components, which are summarized in **FIGURE 1**. If the initial evaluation shows the presence of LUTS associated with one or more of the digital rectal examination (DRE) findings suspicious of prostate cancer, hematuria, abnormal prostate-specific antigen (PSA), pain, recurrent infection (infection should be assessed before referral), palpable bladder, or neurologic disease, the patient should be referred to a urologist for additional evaluation before pursuing treatment.4

![](/CMSImagesContent/2016/8/USP1608-BPH-F1.gif)

## **CURRENT TREATMENT GUIDELINES**

The goal of treatment is to relieve LUTS and slow the clinical progression of BPH while improving patient QOL. The 2010 updated treatment guideline from the AUA recommend that if the patient presents with LUTS, with or without uncomplicated prostate enlargement, and the symptoms are not affecting his QOL, then no further evaluation or treatment is recommended. The patient should be reassured and scheduled for a follow-up appointment with his physician if necessary.2 **SIDEBAR 1** presents a case report of a patient with BPH.

## **Sidebar 1. BPH Case Report**

**_Chief Complaint:_**_LF is a 64-year-old white male presenting with fatigue and sleep pattern changes that have lasted over the past several years. He believes his poor sleep habits are due to frequent nighttime urination, occurring three to four times per night. He denies drinking any fluids in the evening. LF also complains of difficulty starting a stream, especially in public restrooms, and notes that this stream has become weaker over time. He also feels that it takes him longer to completely empty his bladder. He admits to "going a little in his shorts" after urinating and confirmed postvoid dribbling. He experiences some mild urgency but denies dysuria. He also confirms knowledge of all of the bathroom locations in his office building._

_**Past Medical History:** LF denies blood in his urine, a past history of STDs, or other UTIs. He reluctantly reports difficulty keeping firm erections during sexual intercourse compared to when he was younger. However, he maintains that this issue is not one of his major concerns._

_**Family History:** Negative family history of prostate cancer_

_**Social History:** Nonsmoker, no illicit drugs, mild alcohol consumption (2-3 beers per week)_

_**Physical Examination:** Male pattern baldness_

_**Vital Signs:** WNL_

_**Genital Examination:**_

_• Circumcised penis without lesions_

_• Two, nontender, normal-sized descended testicles_

_**Digital Rectal Examination:** Normal sphincter tone and hemoccult negative stool_

_• Negative for masses in the rectal vault except for an enlarged, firm prostate without nodules or tenderness_

_• Prostate size estimated to be 35 mL (normal size 20-25 mL)_

_**Labs:**_

_• Total cholesterol: 230 (LDL: 165, HDL: 45, TG: 100)_

_• PSA: 2.34 ng/mL (normal 0.0-4.0 ng/mL)_

_• TSH: WNL_

_• CMP/CBC: WNL_

_**Prescription Medications:** None_

_**Nonprescription Medications:**_

_• Niacin 1,000 mg 1 daily_

_• Cinnamon tablet 1 daily_

_**Treatment:** Therapy options were first discussed with LF, which included observation with lifestyle modifications and pharmacotherapy. Due to its invasive nature, surgical interventions should be discussed when there has been a failure of the less invasive treatments. Since LF's presentation was not suggestive of prostate cancer (e.g., an elevated PSA >4.0 or the presence of nodules on the prostate during the examination), a biopsy of the prostate was not indicated. LF was started on finasteride 5 mg once daily. After about 2 months, he reported improved urinary flow, less nocturia, and an improved sleep pattern with less daytime fatigue. His only side effects were a slightly diminished libido and an occasional retrograde ejaculation._

_**Discussion:** Finasteride was indicated in LF due to its benefit of decreasing prostate size while improving maximum urinary flow rate and associated LUTS. In addition, it is also indicated for male pattern baldness. Alpha-blockers could also be considered in this patient, with the added benefit of a quicker response by dilating the prostatic urethra, although with the possible result of a higher prevalence of retrograde ejaculation. Another option discussed with LF was the use of tadalafil. However, he did not express significant interest regarding the need for improvement of erectile dysfunction. If LF does not respond to the currently prescribed therapy, urodynamic studies could be ordered, which would evaluate the actual flow kinetics of the urine through the prostate and also the amount of residual urine in the bladder after micturition. The results of these tests could then lead to a referral to a urologist in anticipation of one of the various surgical procedures such as TURP._

_BPH: benign prostatic hyperplasia; CMP/CBC: complete metabolic profile/complete blood count; HDL: high-density lipoprotein; LDL: low-density lipoprotein; PSA: prostate-specific antigen; STD: sexually transmitted disease; TG: triglyceride; TSH: thyroid-stimulating hormone; TURP: transurethral resection of the prostate; UTI: urinary tract infection; WNL: within normal limits._

## **Watchful Waiting**

Watchful waiting or active surveillance is recommended for men who begin experiencing mild symptoms related to BPH. The physician and patient should discuss potential treatment options, including benefits and risks associated with each alternative, and identify a choice treatment based on shared decision-making.2 Additional optional evaluations could also be pursued at this time. In general, watchful waiting is appropriate in patients who are experiencing some symptoms that have not yet begun to affect their daily life.2

## **Lifestyle Modifications**

If patients present with bothersome LUTS that begin affecting their QOL, lifestyle modifications should be recommended initially. Common lifestyle modifications and behavior recommendations include nightly fluid restriction, timed bladder voiding, double-voiding techniques, regular physical activity, treatment of constipation, and avoiding caffeine, alcohol, and highly seasoned or irritative foods.5 These recommendations help to improve symptoms and prevent progression of symptoms to the point of requiring pharmacotherapy or surgery.

## **Pharmacotherapy**

If lifestyle modifications are insufficient in improving QOL, then pharmacotherapy may be indicated in patients who do not have absolute indications warranting surgery.5 Current oral pharmacotherapy options for managing BPH include alpha-adrenergic antagonists (alpha-blockers), 5-alpha-reductase inhibitors (5ARIs), muscarinic receptor antagonists (MRAs), and phosphodiesterase 5 (PDE5) inhibitors.6 A summary of the available agents in each class can be found in **TABLE 1**.5,6

![](/CMSImagesContent/2016/8/USP1608-BPH-T1.gif)

**_Alpha-Blockers:_**__ This class of medications is indicated for the treatment of patients with moderate-to-severe symptomatic BPH regardless of prostate size.5 Alpha-blockers work by blocking the alpha-adrenoceptors on the smooth muscle of the prostate, prostatic urethra, and bladder neck, leading to decreased muscle tone and reduction in bladder obstruction.5 All available alpha-blockers have comparable efficacy when given at appropriate doses and can help to improve urinary flow rate after a few hours or days after administration. The most common class-related adverse events are summarized in **TABLE 1**.5,6

In particular, intraoperative floppy iris syndrome (IFIS; i.e., poor pupil dilation and sudden constriction) is an ocular adverse event that may occur in those undergoing cataract surgery.5 Alpha-blocker treatment should be discontinued prior to cataract surgery and restarted once surgery is complete.5 Orthostatic hypo-tension with dizziness may also occur due to vasodilation induced by blockage of alpha-adrenergic receptors. Thus, caution should be exercised in those taking antihypertensive agents or with cardiovascular comorbidities. Vasodilatory effects are more commonly seen with doxazosin and terazosin, and are less common with alfuzosin, tamsulosin, and silodosin.7

Patients should be counseled to take alfuzosin, tamsulosin, and silodosin with or immediately after the same meal each day, and to swallow the capsule whole without crushing, chewing, or opening the contents.8-10 Tamsulosin capsule contents may be mixed with a small amount of acidic fruit juice or soft food when necessary, while silodosin should only be mixed with applesauce.9,10 Doxazosin and terazosin can be taken without regard to meals. In addition, patients should be cautious when stretching or moving suddenly from a sitting to a standing position in order to avoid orthostatic hypotension.11,12

**_5ARIs:_**__ These medications (dutasteride, finasteride) are also recommended for patients with moderate-to-severe symptomatic BPH in addition to an enlarged prostate. An enlarged prostate is defined by gland size >25 mL and/or PSA levels >1.5 ng/mL based on clinical trials.2 5ARIs have also been shown to decrease both serum dihydrotestosterone (DHT) and PSA levels, improving maximum urinary flow rate and LUTS with no difference in clinical efficacy between agents.2,13

A main difference between the two agents is the serum half-life for each, which is 3 to 16 hours for finasteride and 5 weeks for dutasteride.14,15 This may have implications on medication adherence and persistence of adverse effects, which may last well after the discontinuation of the drug.13 Another difference is that finasteride is indicated for male pattern hair loss (androgenetic alopecia), while for dutasteride, it is an off-label use. Both finasteride and dutasteride can be administered with or without food.14,15 In addition, dutasteride capsules must be swallowed whole to avoid irritation of the oropharyngeal mucosa.15

**_MRAs:_** These agents (tolterodine, fesoterodine) are recommended for patients experiencing BPH with OAB symptoms. Symptoms may include irritative LUTS such as urinary urgency, with or without urge incontinence, often with frequency and nocturia.2 MRAs were studied in clinical trials as add-on therapy with alpha-blockers or 5ARIs in cases of OAB associated with BPH. Both tolterodine and fesoterodine demonstrated a significant improvement in storage symptoms, with dry mouth being the most common side effect.16,17 Patients should be counseled to take these agents without regard to meals and swallow the formulations whole.16,17

**_PDE5 Inhibitors:_** There has been growing interest in the use of PDE5 inhibitors alone or in combination with previously mentioned therapies in men experiencing LUTS, regardless of preexisting erectile dysfunction (ED).18 Although the most current update of the AUA guideline for BPH management does not mention treatment with PDE5 inhibitors, the 2013 European Association of Urology (EAU) guidelines report that these agents (i.e., tadalafil, sildenafil, and vardenafil) can be utilized to quickly decrease urinary symptoms and also improve ED.7,18 Tadalafil currently has a labeled indication for BPH and should be administered around the same time each day without regard to meals.19

**_Combination Therapy:_**__ Also available on the market is a fixed-dose combination product of dutasteride (5ARI) plus tamsulosin (alpha-blocker), which is approved for the symptomatic management of BPH.20 Clinical trials have shown that the synergistic effect of the dual mechanisms of action is significantly superior to tamsulosin and dutasteride monotherapy in symptom improvement as well as reducing BPH clinical progression in men with enlarged prostates.20 Adverse events were consistent with those seen in monotherapy; however, the frequency of these events was shown to be higher. The AUA guideline recommends the use of this combination therapy in men who have moderate-to-severe symptomatic BPH, an enlarged prostate, and reduced urine flow rate and are at risk for disease progression.7,20

Recently, there has also been evidence for the combination of PDE5 inhibitors with 5ARI therapy. One study found that tadalafil (PDE5 inhibitor) combined with finasteride (5ARI) led to an improvement in LUTS associated with BPH, regardless of the presence of ED symptoms.21 However, there is currently no drug combination product containing both medications available on the market in the U.S.

**_Phytotherapy:_****** Plant-based or herbal medications have also been used for those experiencing mild-to-moderate LUTS.22 Clinical trials have shown efficacy in the treatment of LUTS; however, many products are not standardized and long-term safety data are not always available.22 Although a number of clinical trials of these products are ongoing, the most updated AUA guideline currently does not recommend the use of phytotherapy or other alternative medicines for the management of LUTS secondary to BPH.2 Commonly seen therapy options may include _Serenoa repens_(saw palmetto), _Pygeum africanum_(tree bark), _Cucurbita pepo_(squash),__ and _Urtica dioica_(stinging nettle)_._ 2,22 It is important to weigh the risks and possible benefits of utilizing alternative treatment.

## **Surgical Treatment**

The 2010 AUA guideline states that surgical intervention is appropriate for individuals with moderate-to-severe LUTS, acute urinary retention, or other complications due to BPH.2 Surgery is the most invasive BPH management strategy. Patients usually fail lifestyle modifications and pharmacotherapy management before proceeding to surgery. Patients may elect to pursue surgery as primary treatment, but the physician and patient should discuss the risks versus benefits and weigh other options.

The AUA guideline recognizes transurethral resection of the prostate (TURP), which involves boring a larger passageway through the center of the prostate allowing for better flow of urine, as the benchmark therapy among the surgical options. In addition, an open prostatectomy may be reserved for men with very enlarged prostate glands (volume >80-100 mL), bladder diverticula, or bladder stones.2

## **

 

  
PHARMACIST'S ROLE**

Pharmacists have the training required to provide expert advice and recommendations for medication therapy. Pharmacists in the community setting, in particular, are an accessible source of healthcare information to the inquiring BPH patient population (**SIDEBAR 2**). It is important for pharmacists to understand the terminology and symptoms associated with BPH in order to engage in knowledgeable discussions with patients regarding therapy options. In addition, counseling for BPH medications should include a review of risks and possible adverse effects, which are summarized in **TABLE 1**. Overall, BPH is a common disease state in the aging male population, and pharmacists play an important role in management due to the increased chances of encountering related questions from the community.

![](/CMSImagesContent/2016/8/USP1608-BPH-T2.gif)

### **REFERENCES**

1\. Roehrborn CG. Benign prostatic hyperplasia: an overview. _Rev Urol_. 2005;7(suppl 9):S3-S14.  
2\. McVary KT, Roehrborn CG, Avins AL, et al. _American Urological Association Guideline: Management of Benign Prostatic Hyperplasia (BPH)_. Linthicum, MD: American Urological Association; 2010:1-62, Appendix 278-285. www.auanet.org/education/guidelines/benign-prostatic-hyperplasia.cfm. Accessed March 14, 2016.  
3\. Lepor H. Pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia. _Rev Urol_. 2004;6(suppl 9):S3-S10.  
4\. Abrams P, Chapple C, Khoury S, et al. Evaluation and treatment of lower urinary tract symptoms in older men. _J Urol_. 2009;181(4):1779-1787.  
5\. Fonseca J, Martins da silva C. The diagnosis and treatment of lower urinary tract symptoms due to benign prostatic hyperplasia with α-blockers: focus on silodosin. _Clin Drug Investig_. 2015;35(suppl 1):7-18.  
6\. Wang X, Wang X, Li S, et al. Comparative effectiveness of oral drug therapies for lower urinary tract symptoms due to benign prostatic hyperplasia: a systematic review and network meta-analysis. _PLoS One_. 2014;9(9):e107593.  
7\. Gratzke C, Bachmann A, Descazeaud A, et al. EAU guidelines on the management of non-neurogenic male lower urinary tract symptoms (LUTS), including benign prostatic obstruction. _Eur Urol_. 2015;67(6):1099-1109.  
8\. Uroxatral (alfuzosin) package insert. Cary, NC: Covis Pharmaceuticals, Inc; September 2013.  
9\. Flomax (tamsulosin) package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; October 2014.  
10\. Rapaflo (silodosin) package insert. Corona, CA: Watson Pharmaceuticals, Inc; January 2013.  
11\. Cardura (doxazosin) package insert. New York, NY: Pfizer; October 2001.  
12\. Hytrin (terazosin) package insert. North Chicago, IL: Abbott Laboratories; July 2009.  
13\. Carrasquillo RJ, Nealy SW, Wang DS. 5-Alpha-reductase inhibitors in diseases of the prostate. _Curr Opin Endocrinol Diabetes Obes_. 2014;21(6):488-492.  
14\. Proscar (finasteride) package insert. Whitehouse Station, NJ: Merck & Co, Inc; January 2014.  
15\. Avodart (dutasteride) package insert. Research Triangle Park, NC: GlaxoSmithKline; October 2011.  
16\. Detrol (tolterodine tartrate) package insert. New York, NY: Pharmacia & Upjohn Co, division of Pfizer; February 2011.  
17\. Toviaz (fesoterodine fumarate) package insert. New York, NY: Pfizer, Inc; August 2012.  
18\. Gacci M, Carini M, Salvi M, et al. Management of benign prostatic hyperplasia: role of phosphodiesterase-5 inhibitors. _Drugs Aging_. 2014;31(6):425-439.  
19\. Cialis (tadalafil) package insert. Indianapolis, IN: Lilly ICOS, LLC; October 2011.  
20\. Dimitropoulos K, Gravas S. Fixed-dose combination therapy with dutasteride and tamsulosin in the management of benign prostatic hyperplasia. _Ther Adv Urol_. 2016;8(1):19-28.  
21\. Glina S, Roehrborn CG, Esen A, et al. Sexual function in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia: results of a 6-month, randomized, double-blind, placebo-controlled study of tadalafil coadministered with finasteride. _J Sex Med_. 2015;12(1):129-138.  
22\. Allkanjari O, Vitalone A. What do we know about phytotherapy of benign prostatic hyperplasia? _Life Sci._ 2015;126:42-56.  
23\. Jalyn (dutasteride and tamsulosin) capsule package insert. Research Triangle Park, NC: GlaxoSmithKline; January 2015.

To comment on this article, contact rdavidson@uspharmacist.com.

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# Cialis for BPH: What You Should Know

Posted on September 15, 2024

Do you wake up at night with an urgent need to urinate? We understand how frustrating it is to have constant interruptions and discomfort from benign prostatic hyperplasia (BPH).

We are here to help you find relief and reclaim your peace. With our deep expertise in managing BPH symptoms, we offer solutions that truly work, such as Cialis for BPH.

Cialis is an oral medication that helps relax the muscles and increase blood flow to the penis, prostate, and bladder, allowing urine to flow more freely.

Next, we explore Cialis treatment for BPH, its impact on urinary and sexual health, and potential side effects.

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## Understanding BPH

BPH is characterized by an enlarged prostate, which can range in severity. It is usually caused by natural aging and hormonal changes, but other [BPH causes](https://www.gaprostate.com/what-is-bph/bph-causes/) include cell growth, inflammation, and lifestyle or neurological factors.

Some men experience mild [BPH symptoms](https://www.gaprostate.com/bph-symptoms/) that are easily managed with lifestyle changes, such as:

  * Modifying your diet.
  * Managing your fluid intake.
  * Following a set urination schedule.



For others, further medical intervention is necessary for symptom relief. Talk to your healthcare provider, as they may recommend medications, like Cialis that may offer relief.

## Cialis for BPH

Cialis (generic name tadafil) was originally developed to help men living with erectile dysfunction.

However, it was FDA-approved in 2011 for BPH treatment after studies1 revealed a once-daily Cialis for BPH dosage helped relieve lower urinary tract symptoms (LUTS) when given over a 12-week period.

Researchers tested several Cialis daily dosage levels, including 5, 10, and 20mg. They concluded that a low dose of Cialis for BPH (a 5 mg daily) delivered maximum relief with minimal side effects.

## Cialis Impact on Urinary Symptoms

Cialis works by increasing levels of cGMP (cyclic guanosine monophosphate) in the body—a key player in the bodily processes (e.g.,  blood flow to the penis and muscle relaxation in the prostate and bladder) crucial for treating BPH.

Initially developed to enhance sexual function, studies2 have demonstrated its effectiveness in improving urine flow by promoting prostate relaxation.

Additionally, Cialis reduces nighttime urination frequency, offering daily relief from symptoms.

What is the best time of day to take Cialis for BPH? Taking Cialis once daily can significantly alleviate symptom burden. While you can take this medication any time of day, you should try to take it at the same time every day.

## Cialis Impact on Sexual Function

Cialis enhances the release of a key chemical during sexual arousal, increasing blood flow to the penis. This helps you achieve and sustain an erection, facilitating sexual intercourse. Its effects can last for 36 hours after taking the medication, offering greater spontaneity in sexual activity for many men.

## Potential Side Effects of Cialis

For most men, Cialis causes only mild side effects, including:

  * Headaches
  * Nausea
  * Diarrhea
  * Indigestion
  * Back and muscle pain
  * Stuffy nose
  * Facial flushing



However, it can also cause a sudden and potentially dangerous drop in blood pressure. Therefore, men taking nitrates or other blood-pressure-lowering medications should not take Cialis.

## Quality of Life and Patient Satisfaction Post-Treatment

Cialis can improve your quality of life by relieving the painful, frustrating, and uncomfortable urinary symptoms of BPH.

However, if you cannot take Cialis for BPH, or it doesn’t provide sufficient relief, you still have non-surgical options.

At Georgia Prostate Institute, our interventional radiologists offer [Prostate Artery Embolization (PAE)](https://www.gaprostate.com/pae-treatment/), a minimally invasive procedure that helps alleviate lower urinary tract symptoms associated with BPH. PAE avoids large incisions and general anesthesia, reducing the risks and recovery time of traditional prostate surgery.

Are you interested in PAE treatment? [Request a consultation](https://www.gaprostate.com/pae-screening-questions/) with our prostate specialists in Georgia today to explore your options.

## References:

  1. Claus G. Roehrborn, Kevin T. mcVary, Albert Elion-Mboussa, and Lars Viktrup. 2008, October 1). _Tadalafil Administered One Daily for Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A Dose Finding Study._ <https://www.auajournals.org/article/S0022-5347(08)01715-1/fulltext>  
  

  2. Konstantinos Hatzimouratidis. (2014, August). _A review of the use of tadalafil in the treatment of benign prostatic hyperplasia in men with and without erectile dysfunction._ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4054509/



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url: https://pmc.ncbi.nlm.nih.gov/articles/PMC5260456/
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            Current drug therapy of patients with BPH-LUTS with the special emphasis on PDE5 inhibitors - PMC
        

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# Current drug therapy of patients with BPH-LUTS with the special emphasis on PDE5 inhibitors

[Konstantin Kolontarev](https://pubmed.ncbi.nlm.nih.gov/?term=%22Kolontarev%20K%22%5BAuthor%5D)

### Konstantin Kolontarev

1Moscow State University of Medicine and Dentistry, Moscow, Russia

Find articles by [Konstantin Kolontarev](https://pubmed.ncbi.nlm.nih.gov/?term=%22Kolontarev%20K%22%5BAuthor%5D)

1,✉, [Alexander Govorov](https://pubmed.ncbi.nlm.nih.gov/?term=%22Govorov%20A%22%5BAuthor%5D)

### Alexander Govorov

1Moscow State University of Medicine and Dentistry, Moscow, Russia

Find articles by [Alexander Govorov](https://pubmed.ncbi.nlm.nih.gov/?term=%22Govorov%20A%22%5BAuthor%5D)

1, [George Kasyan](https://pubmed.ncbi.nlm.nih.gov/?term=%22Kasyan%20G%22%5BAuthor%5D)

### George Kasyan

1Moscow State University of Medicine and Dentistry, Moscow, Russia

Find articles by [George Kasyan](https://pubmed.ncbi.nlm.nih.gov/?term=%22Kasyan%20G%22%5BAuthor%5D)

1, [Diana Priymak](https://pubmed.ncbi.nlm.nih.gov/?term=%22Priymak%20D%22%5BAuthor%5D)

### Diana Priymak

2Eli Lilly Vostok S.A

Find articles by [Diana Priymak](https://pubmed.ncbi.nlm.nih.gov/?term=%22Priymak%20D%22%5BAuthor%5D)

2, [Dmitry Pushkar](https://pubmed.ncbi.nlm.nih.gov/?term=%22Pushkar%20D%22%5BAuthor%5D)

### Dmitry Pushkar

1Moscow State University of Medicine and Dentistry, Moscow, Russia

Find articles by [Dmitry Pushkar](https://pubmed.ncbi.nlm.nih.gov/?term=%22Pushkar%20D%22%5BAuthor%5D)

1

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1Moscow State University of Medicine and Dentistry, Moscow, Russia

2Eli Lilly Vostok S.A

✉

**Corresponding author** Konstantin Kolontarev, Urology Department of Moscow State University of Medicine and Dentistry, 15/69, Mosfilmovskaya Street, 119330 Moscow, Russia. phone: +79 169 588 265. kb80@yandex.ru

✉

Corresponding author.

Received 2016 Jun 28; Revised 2016 Aug 4; Accepted 2016 Oct 16; Issue date 2016.

Copyright by Polish Urological Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

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PMCID: PMC5260456 PMID: [28127458](https://pubmed.ncbi.nlm.nih.gov/28127458/)

## Abstract

### Introduction

Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptom (LUTS) development in men [1]. The intensity of the symptoms may vary from mild to severe, significantly affecting the quality of life. Erectile dysfunction (ED) is one of the most challenging issues in modern urology that significantly influences the quality of life in men worldwide. The objective of this literature review was to analyze the current drug therapies of patients with BPH-LUTS, with the special emphasis on PDE5 inhibitors.

### Material and methods

The authors searched the literature for the period from 2000 until 2015 in MEDLINE and PubMed.

### Results

Twenty-three articles were selected based on their reliability. A detailed analysis of the selected papers was performed. Primary attention was given to articles describing the use of PDE5. Works describing the use of different groups of drugs in patients with BPH-LUTS were also selected.

### Conclusions

The current literature analysis suggests that the introduction of PDE5 inhibitors in clinical practice for the treatment of patients with BPH-LUTS will allow for significant expansion of the therapeutic options for the treatment of this disease.

**Keywords:** benign prostatic hyperplasia (BPH), erectile dysfunction (ED), PDE5 inhibitors, lower urinary tract symptoms (LUTS)

## INTRODUCTION

Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptom (LUTS) development in men [1]. The intensity of the symptoms may vary from mild to severe, significantly affecting the quality of life (QoL). Approximately 40% of men older than 50 years and 80% older than 80 years are known to have BPH [1]. They report various LUTS, such as weak urine stream, stuttering urination, need to strain during urination, urinary spillage, feeling of incomplete bladder emptying, frequent urination, urination at night (nocturia) and urgency [1].

According to the guidelines AUA and EAU, the first-line therapy for BPH after non-drug treatment is the drug therapy, including alpha-adrenergic antagonists and 5-alpha reductase inhibitors or their combination and PDE-5 inhibitors, as well as other pharmacological groups [2, 3]. Unfortunately, patients develop a significant number of sexual side effects resulting in limited administration of the aforementioned drugs, in many cases, at the expense of efficacy.

Erectile dysfunction (ED) is one of the most challenging issues in modern urology that significantly influences the QoL in men worldwide. Erection as a complex phenomenon involves arterial dilatation, trabecular smooth muscle relaxation and corporal veno-occlusive mechanism activation [4]. ED is a persistent inability to attain and maintain penile erection sufficient to permit sexual performance [5]. The results of the study conducted in 1948 by Kinsey et al. [6] showed that approximately 10 million American men (1 in 10) have ED. Another large-scale epidemiological study was completed in 1994 (Massachusetts Male Aging Study). The authors reported the presence of ED in 52% of men aged 40 to 70 years [7]. In 2012, an epidemiological study was conducted to assess the prevalence of ED in the population of 20- to 75-year-old men in the Russian Federation [8]. The results of the survey showed that 10.1% of responding men had no ED signs, whereas 71.3% had mild, 6.6% had moderate and 12% had severe ED. Therefore, 1101 of 1225 respondents had ED symptoms [8]. A series of studies determined the main predisposing factors of ED development, including hypertensive disease, cardiovascular diseases and diabetes mellitus [9].

Possible mechanisms of LUTS include decreased activity of cyclic guanosine monophosphate (cGMP), RhoA-kinase hyperactivity, chronic ischemia of pelvic organs and hyperactivity of the autonomic nervous system [10]. Administration of PDE5 inhibitors may positively affect all aforementioned proposed mechanisms of LUTS development, resulting in symptoms improvement [11]. Phosphodiesterase type 5 is primarily located in the muscular layer of the urinary bladder neck, prostatic urethra and prostate [12]. Administration of PDE5 inhibitors results in the increase of intracellular cGMP concentration, smooth muscle relaxation and vasodilatation in the urogenital tissues [13].

The objective of this review is to determine the place of PDE5 inhibitors in the individualized approach to only BPH-LUTS treatment with concurrent ED treatment, based on the literature review and personal experience.

## MATERIAL AND METHODS

Two authors (K.K. and G.K.) independently searched the literature for the period from 2000 until 2015 in MEDLINE and PubMed using the following keywords in English: “enlarged prostate, benign prostatic hyperplasia, lower urinary tract symptoms, phosphodiesterase type 5 inhibitors, alpha-adrenergic antagonists, 5-alpha reductase inhibitors and erectile dysfunction”. The discovered works were evaluated and analyzed for feasibility for inclusion in the current review. Primary attention was given to the articles describing the use of PDE5 inhibitors as monotherapy in various groups of patients: patients with BPH-LUTS and patients with concurrent BPH-LUTS and ED. Works describing the use of different groups of drugs in patients with BPH-LUTS were also selected.

Twenty-three articles of highest reliability (inclusion criteria was maximal level of evidence) were selected, 6 of which were dedicated to the monotherapy with PDE5 inhibitors in patients with BPH-LUTS and concurrent BPH-LUTS and ED [18–23]; 4 articles reported monotherapy with alpha-adrenergic antagonists in patients with BPH-LUTS [24–27]; 5 were dedicated to monotherapy with 5-alpha reductase inhibitors in men with BPH-LUTS [28–32]; 7 reported combined therapy with alpha-adrenergic antagonists and PDE5 inhibitors in patients with BPH-LUTS [33–39]; 1 reported combined therapy with alpha-adrenergic antagonists and 5-alpha reductase inhibitors in patients with BPH-LUTS [40]. Thirty-one articles – retrospective works, clinical cases and low reliability publications were excluded from the analysis. The current authors chose tadalafil as the only PDE5 inhibitor registered for BPH treatment, a long-acting drug, to assess the effect of PDE5 inhibitors. As mentioned before, PDE5 is present in the tissue and vessels of the urinary bladder neck, prostatic urethra, prostate and cavernous bodies of penis [12]. Therefore, this enzyme may have significant effect on the pathogenesis of BPH-LUTS. In addition, there is information stating that PDE5 expression in the spinal cord area is responsible for urination control [14]. Tadalafil administration appeared to increase the amount of cyclic nucleotides in the urinary bladder, prostate and cavernous bodies of penis. Such conclusions support the hypothesis about the ability of tadalafil to improve erectile function _via_ the increase in the cGMP level and relaxation of vascular smooth muscle. In addition, the increased cGMP level results in relaxation of the urinary bladder, urethra and prostate, improvement of oxygenation and inhibition of the proliferation of prostate stromal cells [15, 16, 17].

## RESULTS

### Monotherapy with PDE5 inhibitors

Several clinical studies were conducted to assess the efficacy of PDE5 inhibitor administration in patients with concurrent LUTS and ED [18, 19, 20]. International Prostate Symptom Score (IPSS), BPH Impact Index, International Index of Erectile Function (IIEF) scores and Qmax value were used for efficacy assessment. Gacci et al. [21] performed a meta-analysis of the studies comparing PDE5 inhibitor administration and placebo, combined therapy with PDE5 inhibitors and alpha-adrenergic antagonists and monotherapy with alpha-adrenergic antagonists. Dong et al. [18] presented the results of tadalafil monotherapy comparison with placebo. The studies included patients with isolated LUTS and with concomitant ED. Both studies demonstrated significant improvement of IPSS and IIEF scores compared to placebo. Dong et al. [18] noted a significant decrease of total IPSS score by 2.19 points compared to the placebo, in addition to statistically significant improvement of irritative and obstructive domains of IPSS, BPH Impact Index and QoL parameter. No significant improvement of Qmax was noted in any work [21]; however, Dong et al. [18] described a statistically significant change of this parameter in patients receiving tadalafil 5 mg. In this case, different patient enrollment criteria for administration of tadalafil 5 mg (patients with concurrent BPH-LUTS and ED and sexually active patients) were used. Such differences in patient enrollment may explain the different results obtained for Qmax. The lack of the treatment effect on the urodynamic parameters of the urinary bladder contractility during long-term treatment with tadalafil was also demonstrated in the randomized study by Dmochowski et al. [20]. In addition, no significant changes in residual urine was reported during study drug administration [20]. The obtained results suggest other mechanism of LUTS improvement during PDE5 inhibitor administration than mechanic changes. This is well known and allows for the acknowledgement of the complex, yet not completely understood, mechanism of the influence of PDE5 inhibitors on LUTS _via_ increasing the vascularization and reducing ischemia as a result of nitrogen oxide interaction with cGMP, as well as, a decrease in inflammatory and proliferative changes due to RhoA/RhoA-kinase activity [20].

Baseline patient characteristics also influenced the final result of the treatment with PDE5 inhibitors. Gacci et al. [21] performed the regression analysis, which showed that patient age, baseline body mass index and baseline IPSS score significantly influenced the treatment effect. Younger age, low body mass index and higher baseline IPSS score led to a better effect of the treatment with PDE5 inhibitors. Therefore, the ideal patients for treatment with PDE5 inhibitors are young men with high IPSS scores [21]. Porst et al. [19] proved the absence of prostate specific antigen (PSA) level influence on the effect of the treatment with PDE5 inhibitors [19]. The literature data analysis suggests some common pathophysiological mechanisms of LUTS and ED development, in many cases related to the patient age. PDE5 inhibitors block cGMP degradation, thus allowing for excessive relaxation of the smooth muscle of the urinary bladder, prostate and urethra. Administration of tadalafil 5 mg daily as monotherapy is justified in patients with BPH-LUTS with or without concurrent ED [22–23].

### Monotherapy with alpha-adrenergic antagonists

Now, most publications dedicated to the administration of alpha-adrenergic antagonists in patients with LUTS focus on the use of silodosin because this drug is the youngest selective alpha-adrenergic antagonist introduced in clinical practice.

Novara et al. [24] analyzed the results of silodosin registration studies. Data of 1494 patients involved in three 3-month randomized, controlled studies (RCSs) were pooled. Silodosin was more active when compared to the placebo according to the total IPSS score, QoL and Qmax values. The most common side effect was retrograde ejaculation (22%, silodosin group; 0.9%, placebo group). Incidence of dizziness and orthostatic hypotension demonstrated no statistically significant differences between the groups [24]. Further studies showed a moderate positive effect on nocturia in patients with more than 2 episodes of nighttime urination (urination frequency decreased in 61% of cases in the silodosin group _vs._ 49% in the placebo group) [25].

A well-known concept of the treatment of patients with acute urinary retention without a urethral catheter was checked by Kumar et al. [26]. The authors included 60 patients with acute urinary retention in the randomized study. Patients received 8 mg of silodosin daily. The effect of the administered treatment was reported in 77% of patients in the silodosin group and 37% in the placebo group. The presence of more than 800 mL of urine and an IPSS score greater than 25 in patients with acute urinary retention were considered the risk factors of treatment failure [26].

In a 12-week RCS involving 532 patients conducted in Korea, similar efficacy and safety profiles were reported in the patients receiving silodosin 8 mg/day and 2х4 mg/day [27].

It can be concluded that silodosin is effective in the treatment of patients with LUTS. It has an excellent safety profile with respect to cardiovascular complications and significant incidence of retrograde ejaculation.

Administration of alpha-adrenergic antagonists in patients with moderate-to-severe BPH-LUTS is a first-line drug treatment due to its fast onset of action, good efficacy and favorable side effect profile.

### Monotherapy with 5-alpha reductase inhibitors

Safety of dutasteride administration was questioned in the CombAT study due to the high risk of cardiovascular complications reported in dutasteride group when compared to placebo. This fact motivated Locke et al. [28] to conduct a meta-analysis of 12 RCSs (18,802 patients; duration: 6-208 weeks). Dutasteride administration was not associated with increased incidence of heart failure, myocardial infarction or stroke. The authors reported the absence of an apparent relationship between the development of cardiovascular complications and dutasteride administration [28].

The relationship between dutasteride administration and high-risk prostate cancer development is a debatable issue. The Prostate Cancer Prevention Trial study pointed out the increase in the prostate cancer incidence in men consuming a significant volume of alcohol in the group of therapy with 5-alpha reductase inhibitors [29]. Fowke et al. [30] investigated the aforementioned hypothesis using the REDUCE study data. The study enrolled 6374 patients; 25% were not consuming alcohol, 49% were consuming 1 to 7 glasses per week and 26% had severe alcohol dependence (>7 glasses per week). In this study, alcohol intake by the patients in the dutasteride and placebo groups was not associated with the increased incidence of low- and high-risk prostate cancer. However, incidence of high-risk prostate cancer in patients with severe alcohol dependence in the dutasteride group was 86% higher than in non-drinkers. Patients not consuming alcohol demonstrated a reduced incidence of high-risk prostate cancer development. A similar tendency was not reported in the group of patients with severe alcohol dependence. Alcohol consumption had negative effect on the relationship between dutasteride administration and high-risk prostate cancer development [30]. Dutasteride’s effect on nocturia was investigated in several 24-month, phase III studies involving 4321 patients. By the 24th month of drug administration, most patients demonstrated a decrease in nighttime urination frequency when compared to the placebo group (p <0.05). The most significant effect was noted in patients with more than 2 episodes of nighttime urination at baseline [31].

Wada et al. [32] studied the effect in 52 patients receiving dutasteride, in addition to alpha-adrenergic antagonists, if they were not satisfied with their treatment. The authors concluded that long-term dutasteride administration as the adjunct therapy resulted in moderate improvement of the obstructive symptoms.

According to the recommendations of the EAU, 5α-reductase inhibitors should be administered to men with moderate-to-severe LUTS and enlarged prostates (>40 mL) as well as with high PSA level (>1.4–1.6 ng/mL). Due to the slow onset of action, they are suitable for long-term treatment only (many years) [3].

### Combined therapy with alpha-adrenergic antagonists and PDE5 inhibitors

Administration of alpha-adrenergic antagonists is the first-line therapy in patients with BPH-LUTS. Several works suggested the feasibility of therapy with PDE5 inhibitors and alpha-adrenergic antagonists [33–39]. However, administration of this combination seems questionable, considering the potential drug interactions leading to critical blood pressure (BP) lowering. This aspect was studied in several works. Kloner et al. [33] studied the safety of tadalafil combined with 2 different alpha-adrenergic antagonists in a double-blind, placebo-controlled, randomized crossover study. The authors investigated hemodynamic effects during administration of doxazosin 8 mg for 7 days followed by the addition of tadalafil 20 mg and during the administration of tamsulosin 0.4 mg for 7 days followed by the addition of tadalafil 10 and 20 mg. In the first part of the study, patients receiving concomitant doxazosin and tadalafil reported significant lowering of the mean maximum systolic BP compared with placebo. In addition, 3 patients had significant dizziness not correlated with BP values. In the second part of the study (tamsulosin administration in combination with tadalafil), no significant BP lowering was noted after adding tadalafil. Gualiano et al. [34] also did not show significant hemodynamic changes in patients receiving the combination of tadalafil 20 mg and alfuzosin 10 mg daily.

Singh et al. [37] studied the efficacy of combined therapy with tamsulosin 0.4 mg/day and tadalafil 10 mg/day _vs._ monotherapy with each drug. This randomized study included 133 patients with BPH-LUTS. The efficacy of combined therapy (IPSS score) appeared to be higher when compared to monotherapy with tadalafil (p <0.05), but not monotherapy with tamsulosin. Moreover, the efficacy of combined therapy with regard to the ED symptoms (IIEF scale) was higher than in the tamsulosin group.

The aforementioned studies and some others [38, 39] demonstrated the efficacy of combined therapy with PDE5 inhibitors and alpha-adrenergic antagonists in patients with LUTS. Although daily combined therapy with tadalafil 5 mg and alpha-adrenergic antagonist is promising, no results of any randomized, double-blind study, in which conduct is very important, have been published.

Thus, the concomitant administration of tadalafil and the nonselective alpha-adrenergic antagonist doxazosin is contraindicated, whereas concomitant administration of tadalafil and selective alpha-adrenergic antagonists is possible in certain clinical cases (with necessary precautions).

### Combined therapy with alpha-adrenergic antagonists and 5-alpha reductase inhibitors

The role of combined therapy with alpha-adrenergic antagonists and 5-alpha reductase inhibitors is well studied, and the combination is recommended for the treatment of moderate-to-severe BPH-LUTS in patients with an apparent risk of progression by all main clinical guidelines.

MTOPS was the first study to assess combined therapy with alpha-adrenergic antagonists and 5-alpha reductase inhibitors, for which the results were published over 10 years ago. Fwu et al. analyzed the results of this study in 2013. In their work, they studied the effect of monotherapy and combined therapy based on the results from various QoL tools and the effect on sexual function using Brief Male Sexual Function Inventory within the 4-year study [40]. Treatment with finasteride and combined therapy resulted in sexual function worsening, whereas doxazosin administration had minimal negative effect.

These data support EAU recommendations for dutasteride and tamsulosin combination administration in patients at high risk for disease development (higher prostate volume, low Qmax and high PSA) [3].

There are some limitations including the brief discussion of different combinations for BPH therapy, silodosin as the only discussed alpha-blocker and absence in this review of some drug groups (muscarinic receptor antagonists and beta-3 agonists). This was done due to the strong limitation of the text size.

## CONCLUSIONS

Specialists can evaluate various factors to choose a particular drug treatment for patients with BPH-LUTS, including the degree of the symptom severity, concurrent diseases, the possibility of therapeutic effect on the symptoms and patient’s QoL and the potential development of side effects associated with certain drugs. Despite the fact that no new drug for the treatment of LUTS was registered during the past 24 months, studies conducted within this period make us take a fresh look at the old principles. The performed analysis suggests the possibility for implementation of individualized medicine principles, allowing for the selection of the most effective drug or drug combination in each specific case.

The current literature analysis suggests that the introduction of PDE5 inhibitors in clinical practice for the treatment of patients with BPH-LUTS will allow for significant expansion of the therapeutic options for the treatment of this disease.

## CONFLICTS OF INTEREST

Diana Priymak is an employee of Eli Lilly and Company. No other authors have any conflicts of interest to disclose.

## References

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title: Benign Prostatic Hyperplasia (BPH) Guideline - American Urological Association
scrape_date: 2025-02-28T17:23:19.677179
content_type: markdown
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https://www.auanet.org/guidelines-and-quality/guidelines/benign-prostatic-hyperplasia-(bph)-guideline

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        * [ Japan ](/meetings-and-education/global-academic-exchanges/exchange-programs/japan "Japan")
        * [ USI ](/meetings-and-education/global-academic-exchanges/exchange-programs/usi "USI")
      * [ Visiting Scholar Programs ](/meetings-and-education/global-academic-exchanges/visiting-scholar-programs "Visiting Scholar Programs") __
        * [ CAU ](/meetings-and-education/global-academic-exchanges/visiting-scholar-programs/cau "CAU")
        * [ France ](/meetings-and-education/global-academic-exchanges/visiting-scholar-programs/france "France")
        * [ Mexico ](/meetings-and-education/global-academic-exchanges/visiting-scholar-programs/mexico "Mexico")
      * [ Resident Programs ](/meetings-and-education/global-academic-exchanges/resident-programs "Resident Programs")
      * [ Current Scholars ](/meetings-and-education/global-academic-exchanges/current-scholars "Current Scholars")
      * [ Past Participants ](/meetings-and-education/global-academic-exchanges/past-participants "Past Participants")
    * [ For Medical Students ](/meetings-and-education/for-medical-students/medical-students-curriculum-x18427) __
      * [ Medical Students Curriculum ](/meetings-and-education/for-medical-students/medical-students-curriculum-x18427 "Medical Students Curriculum") __
        * [ Acute Scrotum ](/meetings-and-education/for-medical-students/medical-students-curriculum/acute-scrotum "Acute Scrotum")
        * [ Adult UTI ](/meetings-and-education/for-medical-students/medical-students-curriculum/adult-uti "Adult UTI")
        * [ Basic Communication Skills ](/meetings-and-education/for-medical-students/medical-students-curriculum/basic-communication-skills "Basic Communication Skills")
        * [ Bladder Drainage ](/meetings-and-education/for-medical-students/medical-students-curriculum/bladder-drainage "Bladder Drainage")
        * [ BPH ](/meetings-and-education/for-medical-students/medical-students-curriculum/bph "BPH")
        * [ ED ](/meetings-and-education/for-medical-students/medical-students-curriculum/ed "ED")
        * [ Hematuria ](/meetings-and-education/for-medical-students/medical-students-curriculum/hematuria "Hematuria")
        * [ Kidney Stones ](/meetings-and-education/for-medical-students/medical-students-curriculum/kidney-stones "Kidney Stones")
        * [ Male Infertility ](/meetings-and-education/for-medical-students/medical-students-curriculum/male-infertility "Male Infertility")
        * [ Pediatric Oncology ](/meetings-and-education/for-medical-students/medical-students-curriculum/pediatric-oncology "Pediatric Oncology")
        * [ Pediatric UTI ](/meetings-and-education/for-medical-students/medical-students-curriculum/pediatric-uti "Pediatric UTI")
        * [ Pelvic and Bladder Pain ](/meetings-and-education/for-medical-students/medical-students-curriculum/pelvic-and-bladder-pain "Pelvic and Bladder Pain")
        * [ Prostate Cancer/PSA ](/meetings-and-education/for-medical-students/medical-students-curriculum/prostate-cancer/psa "Prostate Cancer/PSA")
        * [ Transgender and Gender Diverse Patient Care ](/meetings-and-education/for-medical-students/medical-students-curriculum/transgender-and-gender-diverse-patient-care "Transgender and Gender Diverse Patient Care")
        * [ Upper Tract Urothelial Carcinoma ](/meetings-and-education/for-medical-students/medical-students-curriculum/upper-tract-urothelial-carcinoma "Upper Tract Urothelial Carcinoma")
        * [ Urologic Emergencies ](/meetings-and-education/for-medical-students/medical-students-curriculum/urologic-emergencies "Urologic Emergencies")
        * [ Urinary Incontinence ](/meetings-and-education/for-medical-students/medical-students-curriculum/urinary-incontinence "Urinary Incontinence")
        * [ Urethral Strictures ](/meetings-and-education/for-medical-students/medical-students-curriculum/urethral-strictures "Urethral Strictures")
      * [ Why Urology? ](about-us/aua-overview/why-urology)
      * [ Residency ](meetings-and-education/for-residents)
      * [ Summer Fellowships ](research-and-data/research-awards/aua-funding/medical-student-fellowships)
      * [ GU Exams ](/meetings-and-education/for-medical-students/gu-exams "GU Exams") __
        * [ Male GU Exam ](/meetings-and-education/for-medical-students/gu-exams/male-gu-exam "Male GU Exam")
        * [ Female GU Exam ](/meetings-and-education/for-medical-students/gu-exams/female-gu-exam "Female GU Exam")
        * [ Pediatric GU Exam ](/meetings-and-education/for-medical-students/gu-exams/pediatric-gu-exam "Pediatric GU Exam")
      * [ Medical Student Resources ](/meetings-and-education/for-medical-students/medical-student-resources "Medical Student Resources") __
        * [ Resources for URiM and URiU Medical Students ](x18662.xml)
    * [ For Residents ](/meetings-and-education/for-residents) __
      * [ For Residency Program Directors ](/meetings-and-education/for-residents/for-residency-program-directors "For Residency Program Directors")
      * [ Urology Residency & Fellowship Programs ](/meetings-and-education/for-residents/urology-residency-and-fellowship-programs "Urology Residency & Fellowship Programs") __
        * [ Accredited U.S. Urology Programs ](/meetings-and-education/for-residents/urology-residency-and-fellowship-programs/accredited-us-urology-programs "Accredited U.S. Urology Programs") __
          * [ Accredited Listing of U.S. Urology Residency Programs ](/meetings-and-education/for-residents/urology-residency-and-fellowship-programs/accredited-us-urology-programs/accredited-listing-of-us-urology-residency-programs "Accredited Listing of U.S. Urology Residency Programs")
        * [ Program Vacancies ](/meetings-and-education/for-residents/urology-residency-and-fellowship-programs/program-vacancies "Program Vacancies") __
          * [ Program Vacancy Submission Form ](/meetings-and-education/for-residents/urology-residency-and-fellowship-programs/program-vacancies/program-vacancy-submission-form "Program Vacancy Submission Form")
          * [ Urology Vacancies ](meetings-and-education/for-residents/urology-residency-and-fellowship-programs/program-vacancies/urology-vacancies)
        * [ Fellowships Societies ](membership/membership-committees/residents-and-fellows-committee/fellowships)
        * [ Additional Fellowships for Internationals ](/meetings-and-education/for-residents/urology-residency-and-fellowship-programs/additional-fellowships-for-internationals "Additional Fellowships for Internationals")
      * [ Urology and Specialty Matches ](/meetings-and-education/for-residents/urology-and-specialty-matches "Urology and Specialty Matches") __
        * [ Specialty Match Timelines ](/meetings-and-education/for-residents/urology-and-specialty-matches/specialty-match-timelines "Specialty Match Timelines") __
          * [ MatchProgramTraining ](/meetings-and-education/for-residents/urology-and-specialty-matches/specialty-match-timelines/matchprogramtraining "MatchProgramTraining")
      * [ Examination Resources ](/meetings-and-education/for-residents/examination-resources "Examination Resources")
    * [ Course Planning, Disclosures and CME ](/meetings-and-education/course-planning-disclosures-and-cme) __
      * [ Confidentiality Statement for Online Education ](/meetings-and-education/course-planning-disclosures-and-cme/confidentiality-statement-for-online-education "Confidentiality Statement for Online Education")
      * [ Continuing Medical Education & Accreditation ](/meetings-and-education/course-planning-disclosures-and-cme/continuing-medical-education-and-accreditation "Continuing Medical Education & Accreditation") __
        * [ AUA Continuing Education (CE) Mission Statement ](/meetings-and-education/course-planning-disclosures-and-cme/continuing-medical-education-and-accreditation/aua-continuing-education-\(ce\)-mission-statement "AUA Continuing Education \(CE\) Mission Statement")
        * [ CME Frequently Asked Questions ](/meetings-and-education/course-planning-disclosures-and-cme/continuing-medical-education-and-accreditation/cme-frequently-asked-questions "CME Frequently Asked Questions")
      * [ Activity Suggest Form ](/meetings-and-education/course-planning-disclosures-and-cme/activity-suggest-form "Activity Suggest Form")
      * [ Submit a Course for Annual Meeting ](/meetings-and-education/course-planning-disclosures-and-cme/submit-a-course-for-annual-meeting "Submit a Course for Annual Meeting")
      * [ Section Meeting Request for Course of Choice ](/meetings-and-education/course-planning-disclosures-and-cme/section-meeting-request-for-course-of-choice "Section Meeting Request for Course of Choice")
      * [ Disclosures ](/meetings-and-education/course-planning-disclosures-and-cme/disclosures "Disclosures") __
        * [ AUA Disclosure Policy ](/meetings-and-education/course-planning-disclosures-and-cme/disclosures/aua-disclosure-policy "AUA Disclosure Policy")
      * [ Definition of CME ](/meetings-and-education/course-planning-disclosures-and-cme/definition-of-cme "Definition of CME")
      * [ CME Information ](/meetings-and-education/course-planning-disclosures-and-cme/cme-information "CME Information")
    * [ For APP/Allied Health Professionals ](/meetings-and-education/for-app/allied-health-professionals) __
      * [ APP Core Curriculum (Members Only) ](https://auau.auanet.org/courses/published?title=Advanced+Practice+Provider+Core+Curriculum&date_filter_1%5Bmin%5D%5Bdate%5D=&date_filter_1%5Bmax%5D%5Bdate%5D=&field_moc_category_tid=All&field_track_tid=All&field_core_curriculum_tid=All)
      * [ Male GU Exam ](meetings-and-education/for-medical-students/gu-exams/male-gu-exam)
      * [ Female GU Exam ](meetings-and-education/for-medical-students/gu-exams/female-gu-exam)
      * [ AUAUniversity Podcasts ](https://soundcloud.com/auauniversity/sets/app-podcast-playlist)
      * [ Advanced Practice Providers Speaker's Bureau ](/meetings-and-education/for-app/allied-health-professionals/advanced-practice-providers-speakers-bureau "Advanced Practice Providers Speaker's Bureau")

  * [Guidelines & Quality](/guidelines-and-quality) __

![](/PreBuilt/ui-assets/images/placeholder-guidelines-3.jpg)

    * [ Guidelines ](/guidelines-and-quality/guidelines) __
      * [ Non-Oncology Guidelines ](/guidelines-and-quality/guidelines/non-oncology-guidelines "Non-Oncology Guidelines") __
        * [ Additional Topics ](/guidelines-and-quality/guidelines/non-oncology-guidelines/additional-topics "Additional Topics")
        * [ Incontinence ](/guidelines-and-quality/guidelines/non-oncology-guidelines/incontinence "Incontinence")
        * [ Pediatric Urology ](/guidelines-and-quality/guidelines/non-oncology-guidelines/pediatric-urology "Pediatric Urology")
        * [ Sexual and Reproductive Health ](/guidelines-and-quality/guidelines/non-oncology-guidelines/sexual-and-reproductive-health "Sexual and Reproductive Health")
        * [ Stones ](/guidelines-and-quality/guidelines/non-oncology-guidelines/stones "Stones")
      * [ Oncology Guidelines ](/guidelines-and-quality/guidelines/oncology-guidelines "Oncology Guidelines") __
        * [ Bladder Cancer ](/guidelines-and-quality/guidelines/oncology-guidelines/bladder-cancer "Bladder Cancer")
        * [ Prostate Cancer ](/guidelines-and-quality/guidelines/oncology-guidelines/prostate-cancer "Prostate Cancer")
        * [ Renal Cancer ](/guidelines-and-quality/guidelines/oncology-guidelines/renal-cancer "Renal Cancer")
        * [ Testicular Cancer ](/guidelines-and-quality/guidelines/oncology-guidelines/testicular-cancer "Testicular Cancer")
      * [ Translated Guidelines ](/guidelines-and-quality/guidelines/translated-guidelines "Translated Guidelines")
    * [ Quality and Measurement ](/guidelines-and-quality/quality-and-measurement) __
      * [ Quality Improvement ](/guidelines-and-quality/quality-and-measurement/quality-improvement "Quality Improvement") __
        * [ Diagnostic Excellence ](/guidelines-and-quality/quality-and-measurement/quality-improvement/diagnostic-excellence "Diagnostic Excellence")
        * [ Engage with Quality Improvement and Patient Safety (E-QIPS) ](/guidelines-and-quality/quality-and-measurement/quality-improvement/engage-with-quality-improvement-and-patient-safety-\(e-qips\) "Engage with Quality Improvement and Patient Safety \(E-QIPS\)") __
          * [ E-QIPS Initiative Request Forms ](/guidelines-and-quality/quality-and-measurement/quality-improvement/engage-with-quality-improvement-and-patient-safety-\(e-qips\)/e-qips-initiative-request-forms "E-QIPS Initiative Request Forms")
        * [ Quality Improvement Summit ](/guidelines-and-quality/quality-and-measurement/quality-improvement/quality-improvement-summit "Quality Improvement Summit")
        * [ Clinical Consensus Statement and Quality Improvement Issue Brief (CCS & QIIB) ](/guidelines-and-quality/quality-and-measurement/quality-improvement/clinical-consensus-statement-and-quality-improvement-issue-brief-\(ccs-and-qiib\) "Clinical Consensus Statement and Quality Improvement Issue Brief \(CCS & QIIB\)")
        * [ Quality Improvement Resource Library ](/guidelines-and-quality/quality-and-measurement/quality-improvement/quality-improvement-resource-library "Quality Improvement Resource Library") __
          * [ Improving Advanced Prostate Cancer Patient Management and Care Coordination ](https://www.pfizeroncologycongresshub.com/files/Final-RC-PP-XDI-USA-0318Steps-to-Success-Postcard.pdf)
          * [ AUA Quality Improvement Webinar Video ](/guidelines-and-quality/quality-and-measurement/quality-improvement/quality-improvement-resource-library/aua-quality-improvement-webinar-video "AUA Quality Improvement Webinar Video")
          * [ FDA Alerts and Recalls ](/guidelines-and-quality/quality-and-measurement/quality-improvement/quality-improvement-resource-library/fda-alerts-and-recalls "FDA Alerts and Recalls")
      * [ Measurement ](/guidelines-and-quality/quality-and-measurement/measurement "Measurement") __
        * [ Overview of MIPS Value Pathways (MVPs) and the New Urology MVP ](/guidelines-and-quality/quality-and-measurement/measurement/overview-of-mips-value-pathways-\(mvps\)-and-the-new-urology-mvp "Overview of MIPS Value Pathways \(MVPs\) and the New Urology MVP")
        * [ Measurement Primer ](/guidelines-and-quality/quality-and-measurement/measurement/measurement-primer "Measurement Primer")
        * [ 2024 MIPS Toolkit ](/guidelines-and-quality/quality-and-measurement/measurement/2024-mips-toolkit "2024 MIPS Toolkit")
        * [ 2024 MVP Toolkit ](/guidelines-and-quality/quality-and-measurement/measurement/2024-mvp-toolkit "2024 MVP Toolkit")

  * [Leadership & Business](/leadership-and-business) __

![](/images/Leadership/GFlobal%20resLeaderRetreat.jpg)

    * [ Institute for Leadership & Business ](/leadership-and-business/institute-for-leadership-and-business) __
      * [ AUA Leadership Program ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program "AUA Leadership Program") __
        * [ Program Information ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/program-information "Program Information")
        * [ Leadership Mentors ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-mentors "Leadership Mentors") __
          * [ 2025 2026 Mentors ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-mentors/2025-2026-mentors "2025 2026 Mentors")
          * [ 2023 2024 Mentors ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-mentors/2023-2024-mentors "2023 2024 Mentors")
          * [ 2021 2022 Mentors ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-mentors/2021-2022-mentors "2021 2022 Mentors")
          * [ 2018 2019 Mentors ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-mentors/2018-2019-mentors "2018 2019 Mentors")
          * [ 2016 2017 Mentors ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-mentors/2016-2017-mentors "2016 2017 Mentors")
          * [ 2014 2015 Mentors ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-mentors/2014-2015-mentors "2014 2015 Mentors")
          * [ 2012 2013 Mentors ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-mentors/2012-2013-mentors "2012 2013 Mentors")
          * [ 2010 2011 Mentors ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-mentors/2010-2011-mentors "2010 2011 Mentors")
          * [ 2008 2009 Mentors ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-mentors/2008-2009-mentors "2008 2009 Mentors")
          * [ 2006 2007 Mentors ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-mentors/2006-2007-mentors "2006 2007 Mentors")
        * [ Leadership Classes ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-classes "Leadership Classes") __
          * [ 2023 2024 Class ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-classes/2023-2024-class "2023 2024 Class")
          * [ 2021 2022 Class ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-classes/2021-2022-class "2021 2022 Class")
          * [ 2018 2019 Class ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-classes/2018-2019-class "2018 2019 Class")
          * [ 2016 2017 Class ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-classes/2016-2017-class "2016 2017 Class")
          * [ 2014 2015 Class ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-classes/2014-2015-class "2014 2015 Class")
          * [ 2012 2013 Class ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-classes/2012-2013-class "2012 2013 Class")
          * [ 2010 2011 Class ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-classes/2010-2011-class "2010 2011 Class")
          * [ 2008 2009 Class ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-classes/2008-2009-class "2008 2009 Class")
          * [ 2006 2007 Class ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-classes/2006-2007-class "2006 2007 Class")
          * [ 2004 2005 Class ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/leadership-classes/2004-2005-class "2004 2005 Class")
        * [ Activities for the AUA Leadership Program ](/leadership-and-business/institute-for-leadership-and-business/aua-leadership-program/activities-for-the-aua-leadership-program "Activities for the AUA Leadership Program")
      * [ AUA Masterclass in Executive Leadership ](/leadership-and-business/institute-for-leadership-and-business/aua-masterclass-in-executive-leadership "AUA Masterclass in Executive Leadership") __
        * [ AUA Masterclass in Executive Leadership Speakers ](/leadership-and-business/institute-for-leadership-and-business/aua-masterclass-in-executive-leadership/aua-masterclass-in-executive-leadership-speakers "AUA Masterclass in Executive Leadership Speakers")
      * [ Leadership Development Opportunities ](/leadership-and-business/institute-for-leadership-and-business/leadership-development-opportunities "Leadership Development Opportunities") __
        * [ Gallagher Health Policy Scholar ](advocacy/get-involved/scholar-and-fellowship-programs/gallagher-health-policy-scholar-program)
        * [ International Exchange Programs ](meetings-and-education/global-academic-exchanges/exchange-programs)
        * [ International Visiting Scholar Programs ](meetings-and-education/global-academic-exchanges/visiting-scholar-programs)
        * [ Global Residents Leadership Retreat ](/leadership-and-business/institute-for-leadership-and-business/leadership-development-opportunities/global-residents-leadership-retreat "Global Residents Leadership Retreat") __
          * [ 2023 Global Residents Leadership Retreat Photos ](/leadership-and-business/institute-for-leadership-and-business/leadership-development-opportunities/global-residents-leadership-retreat/2023-global-residents-leadership-retreat-photos "2023 Global Residents Leadership Retreat Photos")
          * [ 2023 Participants ](/leadership-and-business/institute-for-leadership-and-business/leadership-development-opportunities/global-residents-leadership-retreat/2023-participants "2023 Participants")
        * [ Urology Scientific Mentoring and Research Training (USMART) ](research-and-data/research-education-and-mentorship-programs/usmart)
        * [ Holtgrewe Legislative Fellow Program ](advocacy/get-involved/scholar-and-fellowship-programs/holtgrewe-legislative-fellowship-program)
        * [ Science & Quality Fellow Program ](research-and-data/research-awards/aua-funding/science-and-quality-fellow-program)
        * [ Speed Mentoring ](/leadership-and-business/institute-for-leadership-and-business/leadership-development-opportunities/speed-mentoring "Speed Mentoring") __
          * [ FUTURE Mentorship Program ](membership/diversity-equity-and-inclusion/dei-program-resources/aua-future-in-urology-mentorship-program)
      * [ Business Education ](/leadership-and-business/institute-for-leadership-and-business/business-education "Business Education") __
        * [ AUA Leadership and Business Podcast ](https://directory.libsyn.com/shows/view/id/3aa8ff9b-ecbc-4367-b86f-e6a4d4daa1f5)
        * [ Brandeis University’s Executive MBA for Physicians ](/leadership-and-business/institute-for-leadership-and-business/business-education/brandeis-universitys-executive-mba-for-physicians "Brandeis University’s Executive MBA for Physicians")
      * [ Practice Management & Coding ](/leadership-and-business/institute-for-leadership-and-business/practice-management-and-coding "Practice Management & Coding") __
        * [ Practice Management & Coding Education ](/leadership-and-business/institute-for-leadership-and-business/practice-management-and-coding/practice-management-and-coding-education "Practice Management & Coding Education")
        * [ CodingToday ](/leadership-and-business/institute-for-leadership-and-business/practice-management-and-coding/codingtoday "CodingToday") __
          * [ Launch CodingToday ](https://aua.codingtoday.com/login.html)
      * [ Urology Practice® ](https://www.auajournals.org/journal/urpr)
    * [ Practice Managers’ Network ](/leadership-and-business/practice-managers-network)
    * [ AUA JobFinder ](https://www.healthecareers.com/aua/search-jobs/)
    * [ AUA CodingToday  ](https://www.auanet.org/leadership-and-business/institute-for-leadership-and-business/practice-management-and-coding/codingtoday)

  * [Advocacy](/advocacy) __

![](/images/Advocacy/landing-page/23_Summit.jpg)

    * [ Action Center ](/advocacy/action-center)
    * [ Federal Advocacy ](/advocacy/federal-advocacy) __
      * [ Physician Payment and Coverage Issues ](advocacy/get-involved/comment-letters-and-resources/physician-payment-and-coverage-issues)
      * [ PSA Testing ](/advocacy/federal-advocacy/psa-testing "PSA Testing")
      * [ Regulatory Burden ](/advocacy/federal-advocacy/regulatory-burden "Regulatory Burden")
      * [ Workforce Shortages ](/advocacy/federal-advocacy/workforce-shortages "Workforce Shortages")
      * [ Reform USPSTF ](/advocacy/federal-advocacy/reform-uspstf "Reform USPSTF")
      * [ Urologic Research ](/advocacy/federal-advocacy/urologic-research "Urologic Research")
      * [ PCa Survivorship ](/advocacy/federal-advocacy/pca-survivorship "PCa Survivorship")
      * [ Medical Liability Reform ](/advocacy/federal-advocacy/medical-liability-reform "Medical Liability Reform")
      * [ IOASE ](/advocacy/federal-advocacy/ioase "IOASE")
      * [ Fertility Priority ](/advocacy/federal-advocacy/fertility-priority "Fertility Priority")
      * [ Bladder Health Priority ](/advocacy/federal-advocacy/bladder-health-priority "Bladder Health Priority")
      * [ Coding and Reimbursement Committee ](/advocacy/federal-advocacy/coding-and-reimbursement-committee "Coding and Reimbursement Committee") __
        * [ Device or Bio Pham Support Request Form ](/advocacy/federal-advocacy/coding-and-reimbursement-committee/device-or-bio-pham-support-request-form "Device or Bio Pham Support Request Form")
        * [ Coding Guidance Request Form ](/advocacy/federal-advocacy/coding-and-reimbursement-committee/coding-guidance-request-form "Coding Guidance Request Form")
        * [ Device or Bio Pharm Support ](/advocacy/federal-advocacy/coding-and-reimbursement-committee/device-or-bio-pharm-support "Device or Bio Pharm Support")
        * [ Request for Coding Guidance ](/advocacy/federal-advocacy/coding-and-reimbursement-committee/request-for-coding-guidance "Request for Coding Guidance")
        * [ Disclaimer ](disclaimer)
      * [ Coding Resources and Information ](/advocacy/federal-advocacy/coding-resources-and-information "Coding Resources and Information")
    * [ State Advocacy ](/advocacy/state-advocacy)
    * [ AUA AMA House of Delegates ](/advocacy/aua-ama-house-of-delegates)
    * [ Get Involved ](/advocacy/get-involved) __
      * Scholar & Fellowship Programs __
        * [ Gallagher Health Policy Scholar Program ](/advocacy/get-involved/scholar-and-fellowship-programs/gallagher-health-policy-scholar-program "Gallagher Health Policy Scholar Program")
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  4. Benign Prostatic Hyperplasia (BPH) Guideline 



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  * Guideline Statement
  * [ 2023 Amendment Panel ](https://www.auanet.org/guidelines-and-quality/guidelines/benign-prostatic-hyperplasia-\(bph\)-guideline#x18765)
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#  Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA Guideline 

## Using AUA Guidelines

This AUA guideline is provided free of use to the general public for academic and research purposes. However, any person or company accessing AUA guidelines for promotional or commercial use must obtain a licensed copy. To obtain the licensable copy of this guideline, please contact Keith Price at [kprice@auanet.org](mailto:kprice@auanet.org).

### (Published 2021; Amended 2023)

The goal of this revised guideline is to provide a useful reference on the effective evidence-based surgical management of male lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH).

**To cite this guideline:**

  * Sandhu JS, Bixler BR, Dahm P, et al. Management of lower urinary tract symptoms attributed to benign prostatic hyperplasia (BPH): AUA Guideline amendment 2023. J Urol. 2023;10.1097/JU.0000000000003698. <https://doi.org/10.1097/JU.0000000000003698>[](https://doi.org/10.1097/JU.0000000000003698)



[Unabridged version of this guideline](documents/Guidelines/PDF/2023%20Guidelines/BPH%20Unabridged%2002-20-24%20Final.pdf) [pdf]  
[Algorithm for this guideline](documents/Guidelines/PDF/2023%20Guidelines/BPH%20Algorithms%20Final%202023.pdf) [pdf]  
[Amendment Summary](documents/Guidelines/PDF/2023%20Guidelines/BPH%202023%20Amendment%20Summary%2009-26-23%20clean.pdf) [pdf]

### Panel Members

Lori B. Lerner, MD; Michael J. Barry, MD; Anurag Kumar Das, MD; Manhar C. Gandhi, MD; Steven A. Kaplan, MD; Tobias S. Kohler, MD; Leslie Martin, MD; J. Kellogg Parsons, MD; Claus G. Roehrborn, MD; John T. Stoffel, MD; Charles Welliver, MD; Kevin T. McVary, MD 

###  2023 Amendment Panel 

Jaspreet S. Sandhu, MD; Ramy Goueli, MD; John T. Stoffel, MD

### Staff and Consultants

Brooke R. Bixler, MPH; Erin Kirkby, MS; Philipp Dahm, MD; Timothy J. Wilt, MD

### 

### SUMMARY

### Purpose

Benign prostatic hyperplasia (BPH) is a histologic diagnosis that refers to the proliferation of smooth muscle and epithelial cells within the prostatic transition zone. The prevalence and the severity of lower urinary tract symptoms (LUTS) in the aging male can be progressive and is an important diagnosis in the healthcare of patients and the welfare of society. In the management of bothersome LUTS, it is important that healthcare providers recognize the complex dynamics of the bladder, bladder neck, prostate, and urethra. Further, symptoms may result from interactions of these organs as well as with the central nervous system or other systemic diseases (e.g., metabolic syndrome, congestive heart failure). Despite the more prevalent (and generally first line) use of medical therapy for men suffering from LUTS attributed to BPH (LUTS/BPH), there remain clinical scenarios where surgery is indicated as the initial intervention for LUTS/BPH and should be recommended, providing other medical comorbidities do not preclude this approach. It is the hope that this revised Guideline will provide a useful reference on the effective evidence-based management of male LUTS/BPH. Please see the accompanying algorithm for a summary of the procedures detailed in the Guideline.

### Methodology

For the surgical management of BPH, the Minnesota Evidence Review Team searched Ovid MEDLINE, the Cochrane Library, and the Agency for Healthcare Research and Quality (AHRQ) database to identify studies indexed between January 2007 and September 2017. Following initial publication in 2018, this Guideline underwent an amendment in 2019 that included literature published through January 2019. An additional literature search was conducted through September 2019 and serves as the basis for a 2020 amendment. The Guideline underwent an additional amendment in 2021 to capture eligible literature published between September 2019 and September 2020.

For the medical management of BPH, the Minnesota Evidence Review Team searched Ovid MEDLINE, Embase, the Cochrane Library, and the AHRQ databases to identify eligible studies published and indexed between January 2008 and April 2019. An updated search was completed to capture studies published between April 2019 and December 2020. Search terms included Medical Subject Headings (MeSH) and keywords for pharmacological therapies, drug classes, and terms related to LUTS or BPH. Limits were used to restrict the search to English language publications. The review team also reviewed articles for inclusion identified by Guideline Panel Members. The guideline was updated in 2023 to capture eligible literature published between September 2020 and October 2022.

When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions.

### GUIDELINE STATEMENTS

### Evaluation

**Initial Evaluation**

  1. In the initial evaluation of patients presenting with bothersome LUTS possibly attributed to BPH, clinicians should obtain a medical history, conduct a physical examination, utilize the International Prostate Symptom Score (IPSS), and perform a urinalysis. (_Clinical Principle_)
  2. Patients should be counseled on options for intervention, which can include behavioral/lifestyle modifications, medical therapy and/or referral for discussion of procedural options. (_Expert Opinion_)



**Follow-up Evaluation**

  3. Patients should be evaluated by their providers 4-12 weeks after initiating treatment (provided adverse events do not require earlier consultation) to assess response to therapy. Revaluation should include the IPSS. Further evaluation may include a post-void residual (PVR) and uroflowmetry. (_Clinical Principle_)
  4. Patients with bothersome LUTS/BPH who elect initial medical management and do not have symptom improvement and/or experience intolerable side effects should undergo further evaluation and consideration of change in medical management or surgical intervention. (_Expert Opinion_)



**Preoperative Testing**

  5. Clinicians should consider assessment of prostate size and shape via transrectal or abdominal ultrasound, cystoscopy, or cross-sectional imaging (i.e., magnetic resonance imaging [MRI]/ computed tomography [CT]) if such studies are available, prior to intervention for LUTS/BPH. (_Clinical Principle_)
  6. Clinicians should perform a PVR assessment prior to intervention for LUTS/BPH. (_Clinical Principle_)
  7. Clinicians should consider uroflowmetry prior to intervention for LUTS/BPH. (_Clinical Principle_)
  8. Clinicians should consider pressure flow studies prior to intervention for LUTS/BPH when diagnostic uncertainty exists. (_Expert Opinion_)
  9. Clinicians should inform patients of the possibility of treatment failure and the need for additional or secondary treatments when considering surgical and minimally-invasive treatments for LUTS/BPH. (_Clinical Principle_)



### Medical Therapy

**Alpha Blockers**

  10. Clinicians should offer one of the following alpha blockers as a treatment option for patients with bothersome, moderate to severe LUTS/BPH: alfuzosin, doxazosin, silodosin, tamsulosin, or terazosin. (_Moderate Recommendation; Evidence Level: Grade A_)
  11. When prescribing an alpha blocker for the treatment of LUTS/BPH, the choice of alpha blocker should be based on patient age and comorbidities, and different adverse event profiles (e.g., ejaculatory dysfunction [EjD], changes in blood pressure). (_Moderate Recommendation; Evidence Level: Grade A_)



**Alpha Blockers and Intraoperative Floppy Iris Syndrome (IFIS)**

  12. When initiating alpha blocker therapy, patients with planned cataract surgery should be informed of the associated risks and be advised to discuss these risks with their ophthalmologists. (_Expert Opinion_)



**5- Alpha Reductase inhibitor (5-ARI)**

  13. For the purpose of symptom improvement, 5-ARI monotherapy should be used as a treatment option in patients with LUTS/BPH with prostatic enlargement as judged by a prostate volume of > 30g on imaging, a prostate specific antigen (PSA) > 1.5ng/mL, or palpable prostate enlargement on digital rectal exam (DRE). (_Moderate Recommendation; Evidence Level: Grade B_)
  14. 5-ARIs alone or in combination with alpha blockers are recommended as a treatment option to prevent progression of LUTS/BPH and/or reduce the risks of urinary retention and need for future prostate-related surgery. (_Strong Recommendation; Evidence Level: Grade A_)
  15. Before starting a 5-ARI, clinicians should inform patients of the risks of sexual side effects, certain uncommon physical side effects, and the low risk of prostate cancer. (_Moderate Recommendation; Evidence Level: Grade C_)
  16. Clinicians may consider 5-ARIs as a treatment option to reduce intraoperative bleeding and peri- or postoperative need for blood transfusion after transurethral resection of the prostate (TURP) or other surgical intervention for BPH. (_Expert Opinion_)



**Phosphodiesterase-5 Inhibitor (PDE5)**

  17. For patients with LUTS/BPH irrespective of comorbid erectile dysfunction (ED), 5mg daily tadalafil should be discussed as a treatment option. (_Moderate Recommendation; Evidence Level: Grade B_)



**Combination Therapy**

  18. 5-ARI in combination with an alpha blocker should be offered as a treatment option only to patients with LUTS associated with demonstrable prostatic enlargement as judged by a prostate volume of > 30g on imaging, a PSA >1.5ng/mL, or palpable prostate enlargement on DRE. (_Strong Recommendation; Evidence Level: Grade A_)
  19. Anticholinergic agents, alone or in combination with an alpha blocker, may be offered as a treatment option to patients with moderate to severe predominant storage LUTS. (_Conditional Recommendation; Evidence Level: Grade C_)
  20. Beta-3-agonists in combination with an alpha blocker may be offered as a treatment option to patients with moderate to severe predominate storage LUTS. (_Conditional Recommendation; Evidence Level: Grade C_)
  21. Clinicians may offer the combination of low-dose daily 5mg tadalafil with alpha blockers for the treatment of LUTS/BPH. (_Conditional Recommendation; Evidence Level: Grade C_)
  22. Clinicians may offer the combination of low dose daily tadalafil 5mg with finasteride for the treatment of LUTS/BPH. (_Conditional Recommendation; Evidence Level: Grade C_)



**Acute Urinary Retention (AUR) Outcomes**

  23. Physicians should prescribe an oral alpha blocker prior to a voiding trial to treat patients with AUR related to BPH. (_Moderate Recommendation; Evidence Level: Grade B_)
  24. Patients newly treated for AUR with alpha blockers should complete at least three days of medical therapy prior to attempting trial without a catheter (TWOC). (_Expert Opinion_)
  25. Clinicians should inform patients who pass a successful TWOC for AUR from BPH that they remain at increased risk for recurrent urinary retention. (_Moderate Recommendation; Evidence Level: Grade C_)



### Surgical Therapy

  26. Surgery is recommended for patients who have renal insufficiency secondary to BPH, refractory urinary retention secondary to BPH, recurrent urinary tract infections (UTIs), recurrent bladder stones or gross hematuria due to BPH, and/or with LUTS/BPH refractory to or unwilling to use other therapies. (_Clinical Principle_)
  27. Clinicians should not perform surgery solely for the presence of an asymptomatic bladder diverticulum; however, evaluation for the presence of bladder outlet obstruction (BOO) should be considered. (_Clinical Principle_)



**Transurethral Resection of the Prostate (TURP)**

  28. TURP should be offered as a treatment option for patients with LUTS/BPH. (_Moderate Recommendation; Evidence Level: Grade B_)
  29. Clinicians may use a monopolar or bipolar approach to TURP as a treatment option, depending on their expertise with these techniques. (_Expert Opinion_)



**Simple Prostatectomy**

  30. Open, laparoscopic, or robotic assisted prostatectomy should be considered as treatment options by clinicians, depending on their expertise with these techniques, only in patients with large to very large prostates. (_Moderate Recommendation; Evidence Level: Grade C_)



**Transurethral Incision of the Prostate (TUIP)**

  31. TUIP should be offered as an option for patients with prostates ≤30g for the surgical treatment of LUTS/BPH. (_Moderate Recommendation; Evidence Level: Grade B_)



**Transurethral Vaporization of the Prostate (TUVP)**

  32. Bipolar TUVP may be offered as an option to patients for the treatment of LUTS/BPH. (_Conditional Recommendation; Evidence Level: Grade B_)



**Photoselective Vaporization of the Prostate (PVP)**

  33. PVP should be offered as an option using 120W or 180W platforms for the treatment of LUTS/BPH. (_Moderate Recommendation; Evidence Level: Grade B)_



**Prostatic Urethral Lift (PUL)**

  34. PUL should be considered as a treatment option for patients with LUTS/BPH provided prostate volume 30-80g and verified absence of an obstructive middle lobe. (_Moderate Recommendation; Evidence Level: Grade C_)
  35. PUL may be offered as a treatment option to eligible patients who desire preservation of erectile and ejaculatory function. (_Conditional Recommendation; Evidence Level: Grade C_)



**Water Vapor Thermal Therapy (WVTT)**

  36. WVTT should be considered as a treatment option for patients with LUTS/BPH provided prostate volume 30-80g. (_Moderate Recommendation; Evidence Level: Grade C_)
  37. WVTT may be offered as a treatment option to eligible patients who desire preservation of erectile and ejaculatory function. (_Conditional Recommendation; Evidence Level: Grade C_)



**Laser Enucleation**

  38. Holmium laser enucleation of the prostate (HoLEP) or thulium laser enucleation of the prostate (ThuLEP) should be considered as an option, depending on the clinician's expertise with these techniques, as prostate size-independent options for the treatment of LUTS/BPH. (_Moderate Recommendation; Evidence Level: Grade B_)



**Robotic Waterjet Treatment (RWT)**

  39. Robotic waterjet treatment (RWT) may be offered as a treatment option to patients with LUTS/BPH provided prostate volume 30-80g. (_Conditional Recommendation; Evidence Level: Grade C_)



**Prostate Artery Embolization (PAE)**

  40. PAE may be offered for the treatment of LUTS/BPH. PAE should be performed by clinicians trained in this interventional radiology procedure following a discussion of the potential risks and benefits. (_Conditional Recommendation: Evidence level: Grade C_)



**Temporary Implanted Prostatic Devices (TIPD)**

  41. TIPD may be offered as a treatment option for patients with LUTS/BPH provided prostate volume is between 25 and 75g and lack of obstructive median lobe. (_Expert Opinion_)



### Hematuria**  
**

  42. After exclusion of other causes of hematuria, 5-ARIs may be an appropriate and effective treatment alternative in men with refractory hematuria presumably due to prostatic bleeding. (_Expert Opinion_)



### Medically Complicated Patients

  43. HoLEP, PVP, and ThuLEP should be considered as treatment options in patients who are at higher risk of bleeding. (_Expert Opinion_)



### 

### INTRODUCTION

### Purpose

BPH is a histologic diagnosis that refers to the proliferation of smooth muscle and epithelial cells within the prostatic transition zone. The prevalence and the severity of LUTS in the aging male can be progressive and is an important diagnosis in the healthcare of patients and the welfare of society. In the management of bothersome LUTS, it is important that healthcare providers recognize the complex dynamics of the bladder, bladder neck, prostate, and urethra. Further, symptoms may result from interactions of these organs as well as with the central nervous system or other systemic diseases (e.g., metabolic syndrome, congestive heart failure). Despite the more prevalent (and often first line) use of medical therapy for men suffering from LUTS/BPH, there remain clinical scenarios where surgery is indicated as the initial intervention for LUTS/BPH and should be recommended, providing other medical comorbidities do not preclude this approach.

It is the hope that this revised Guideline will provide a useful reference on the effective evidence-based management of LUTS/BPH. Please see the accompanying algorithm for a summary of the statements detailed in the Guideline.

### Methodology

In preparation for an update of the Guideline, the Panel provided the Minnesota Evidence-based Practice Center with key questions, interventions, comparators, and outcomes to be addressed. The review team worked closely with the Panel to refine the scope, key questions, and inclusion/exclusion criteria.

The key questions were divided into three topics for surgical management of LUTS/BPH: 1. Preoperative parameters that are necessary before surgical intervention is instituted; 2. Surgical management of BOO attributed to BPH; and 3. AUR.

The key questions were divided into two topics for medical management of BPH: 1. Pharmacological management for LUTS/BPH; and 2. Pharmacological management of AUR attributed to BPH. Select newer medications and the long-term side effects of 5-ARIs were the focus of this report.

#### Panel Formation and Process

The Surgical BPH Panel was created in 2016 by the American Urological Association Education and Research, Inc. The Practice Guidelines Committee (PGC) of the AUA selected the Panel Chairs who in turn appointed the additional panel members with specific expertise in this area. In 2019 and 2022, additional panel members were added to help aid in the combination of the Surgical and Medical BPH Guidelines. Funding of the Guideline was provided by the AUA; panel members received no remuneration for their work.

#### Peer Review

The AUA conducted a thorough peer review process. In 2018, the draft Guideline focusing on surgical management was distributed to 130 peer reviewers of which 58 returned comments. In 2019, the draft Guideline focusing on surgical management was distributed to 74 peer reviewers of which 13 returned comments. In 2020, the draft Guideline focusing on surgical management was distributed to 54 peer reviewers of which nine returned comments. The Panel reviewed and discussed all submitted comments and revised the draft as needed. Once finalized, the Guideline was submitted for approval to the PGC and Science and Quality Council (SQC) and, subsequently, to the AUA Board of Directors for final approval.

In 2021, the draft Guideline inclusive of both medical and surgical management options was distributed to 91 peer reviewers of which 43 returned comments. The Panel reviewed and discussed all submitted comments and revised the draft as needed. Once finalized, the Guideline was submitted for approval to the PGC and SQC and, subsequently, to the AUA Board of Directors for final approval.

In 2023, as a part of the amendment process, the AUA conducted a thorough peer review process. A call for peer reviewers was posted in April 2023 and the draft guideline document was distributed to 66 peer reviewers, 13 of which submitted comments. The Amendment Panel reviewed and discussed all submitted comments and revised the draft as needed. Once finalized, the guideline was submitted for approval to the original guideline panel, the PGC and SQC. It was then submitted to AUA BODs for final approval. Panel members received no renumeration for their work.

#### Searches and Article Selection

For the surgical management of BPH, the Minnesota Evidence Review Team searched Ovid MEDLINE, the Cochrane Library, and the AHRQ database to identify randomized controlled trials (RCTs) and clinical controlled trials (CCTs) published and indexed between January 2007 and September 2017 for key questions relating to preoperative parameters that are necessary before surgical intervention and surgical management of BOO attributed to BPH. For the key question related to AUR, systematic reviews/meta-analyses and observational studies published and indexed between January 2007 and September 2017 were included in the systematic report. Following initial publication in 2018, this Guideline underwent an amendment in 2019 that included literature published through January 2019. An additional literature search was conducted through September 2019 and serves as the basis for a 2020 amendment. The Guideline underwent an additional amendment in 2021 to capture literature published since the 2020 amendment. For the 2021 amendment, AUA's consultant medical librarian utilized the search strategy that was developed by the prior methodology team to identify new peer reviewed publications that have been indexed on PubMed, Embase and the Cochrane Controlled Register of Trials (CENTRAL) database from September 1, 2019 to September 2, 2020. A unique search strategy was used for each of the three topics. Systematic reviews and meta-analyses were searched to identify additional eligible studies. The guideline was updated again in 2023 to capture eligible literature published between September 2020 and October 2022.

For medical management of BPH, the Minnesota Evidence Review Team searched Ovid MEDLINE, Embase, the Cochrane Library, and the AHRQ databases to identify eligible studies published and indexed between January 2008 and April 2019. An additional search was conducted to obtain studies published from April 2019 to December 2020.

Search terms included Medical Subject Headings (MeSH) and keywords for pharmacological therapies, drug classes, and terms related to LUTS or BPH. Limits were used to restrict the search to English language publications. The review team also reviewed articles for inclusion identified by the Panel. Limits were used to restrict the search to English language publications.

Abstract review was completed independently by two investigators to determine if citations were eligible for full text review. Two investigators independently reviewed full text articles to identify studies that met inclusion criteria. Conflicts between investigators on inclusion status were resolved through discussion or by a third investigator when necessary. Note, additional studies published outside of search date ranges may have been included to inform background sections or provide historical context.

#### Assessment of Risk of Bias (ROB) and Data Extraction

A bias is a systematic error in results or inferences that can lead to underestimation or overestimation of the true intervention effect. Differences in ROB can help explain heterogeneity in the results of studies included in a systematic review. ROB domains include random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, and selective reporting. The review team used the Cochrane Collaboration's tool for assessing ROB1 and assessed ROB for the following outcomes: change in IPSS, percent responders based on IPSS (e.g., percentage achieving a minimally detectable difference [MDD] such as a 30-50% reduction in score from baseline or achieving an IPSS score of ≤7 points following treatment), change from baseline in quality of life (IPSS-QoL), perioperative adverse events, and other adverse events (e.g., symptom recurrence, need for reoperation). For blinding of outcome assessment and incomplete outcome data the review team assessed ROB for short-, intermediate-, and long-term follow-up. The overall ROB judgement for each outcome across domains was determined using an approach suggested in the Cochrane Handbook version 5.1.2 ROB was assessed by a single reviewer and quality checked by a subject expert. Discrepancies were resolved by consensus.

#### Data Synthesis and Analysis

Reviewers assessed clinical and methodological heterogeneity to determine appropriateness of pooling data. Data were analyzed in RevMan3 using DerSimonian-Laird random effects to calculate risk ratios (RR) with corresponding 95 percent confidence intervals (95%CI) for binary outcomes and weighted mean differences (WMD) with the corresponding 95%Cis for continuous outcomes. Statistical heterogeneity was assessed with the I2 statistic. If substantial heterogeneity was present (i.e., I2 ≥70%), reviewers stratified the results to assess treatment effects based on patient or study characteristics and/or explored sensitivity analyses. For IPSS and IPSS-QoL, reviewers determined the statistical significance of the effect of interventions versus control but defined clinical efficacy based on whether the mean or median effect between intervention and control exceeded thresholds for clinical significance (i.e., the MDD). For IPSS this is a difference of >3 points. For QoL reviewers defined this as >1 point.

Overall quality of evidence for the primary outcomes within each comparison was evaluated using GRADEpro4 based on five assessed domains.5, 6 The quality of evidence levels range from high to very low. The five domains include the following: 1. Study limitations (ROB); 2. Directness (single, direct link between intervention and outcome); 3. Consistency (similarity of effect direction and size among studies); 4. Precision (degree of certainty around an estimate assessed in relationship to MDD); and 5. Reporting bias.

#### Determination of Evidence Strength

The categorization of evidence strength is conceptually distinct from the quality of individual studies. Evidence strength refers to the body of evidence available for a particular question and includes not only individual study quality but consideration of study design, consistency of findings across studies, adequacy of sample sizes, and generalizability of samples, settings, and treatments for the purposes of the Guideline. The AUA categorizes body of evidence strength as Grade A (well-conducted and highly-generalizable RCTs or exceptionally strong observational studies with consistent findings), Grade B (RCTs with some weaknesses of procedure or generalizability or moderately strong observational studies with consistent findings), or Grade C (RCTs with serious deficiencies of procedure or generalizability or extremely small sample sizes or observational studies that are inconsistent, have small sample sizes, or have other problems that potentially confound interpretation of data). By definition, Grade A evidence is evidence about which the Panel has a high level of certainty, Grade B evidence is evidence about which the Panel has a moderate level of certainty, and Grade C evidence is evidence about which the Panel has a low level of certainty (**Table 1**).

**Table 1: Strength of Evidence Definitions**

[![](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Table%201.PNG)](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Table%201.PNG)

#### AUA Nomenclature: Linking Statement Type to Evidence Strength

The AUA nomenclature system explicitly links statement type to body of evidence strength, level of certainty, magnitude of benefit or risk/burdens, and the Panel's judgment regarding the balance between benefits and risks/burdens**(Table 2)**. **_Strong Recommendations_** are directive statements that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be undertaken because net benefit or net harm is substantial. **_Moderate Recommendations_** are directive statements that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be undertaken because net benefit or net harm is moderate. **_Conditional Recommendations_** are non-directive statements used when the evidence indicates there is no apparent net benefit or harm or when the balance between benefits and risks/burden is unclear. All three statement types may be supported by any body of evidence strength grade. Body of evidence strength Grade A in support of a Strong or Moderate Recommendation indicates the statement can be applied to most patients in most circumstances and that future research is _unlikely to change confidence_. Body of evidence strength Grade B in support of a Strong or Moderate Recommendation indicates the statement can be applied to most patients in most circumstances, but better evidence _could change confidence_. Body of evidence strength Grade C in support of a Strong or Moderate Recommendation indicates the statement can be applied to most patients in most circumstances, but better evidence is _likely to change confidence_. Body of evidence strength Grade C is only rarely used in support of a Strong Recommendation. Conditional Recommendations can also be supported by any evidence strength. When body of evidence strength is Grade A, the statement indicates benefits and risks/burdens appear balanced, the best action depends on patient circumstances, and future research is _unlikely to change confidence_. When body of evidence strength Grade B is used, benefits and risks/burdens appear balanced, the best action also depends on individual patient circumstances, and better evidence _could change confidence_. When body of evidence strength Grade C is used, there is uncertainty regarding the balance between benefits and risks/burdens, alternative strategies may be equally reasonable, and better evidence is _likely to change confidence_.

Where gaps in the evidence existed, **_Clinical Principles_** or **_Expert Opinions_** are provided via consensus of the Panel. A **_Clinical Principle_** is a statement about a component of clinical care widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature. **_Expert Opinion_** refers to a statement based on members' clinical training, experience, knowledge, and judgment for which there may or may not be evidence in the medical literature.

### 

### BACKGROUND

BPH is a histologic diagnosis that refers to the proliferation of glandular epithelial tissue, smooth muscle, and connective tissue within the prostatic transition zone, hence the term "stromo-glandular hyperplasia."7, 8 While several hypotheses exist, BPH is likely the result of a multifactorial process, the exact etiology of which is unknown. What is clearly necessary for the development of BPH, however, is the presence of functioning testes. Eunuchs and men castrated before puberty have atrophic prostate glands and do not develop BPH. That said, testosterone does not act alone. The mechanism by which testosterone exerts many of its physiological effects on the prostate gland is through dihydrotestosterone (DHT). Androgens, including testosterone, are produced by the Leydig cells of the testes and the adrenal glands. After production, testosterone is circulated via the bloodstream to the prostate gland, and then enters into the cells by simple diffusion. Once intracytoplasmic, testosterone is converted to its active metabolite DHT by the enzyme 5 α -reductase, type 2. DHT forms a complex with androgen receptors that is then transported to the nucleus. Within the nucleus, this complex exerts its effects on the transcription of DNA. These effects are necessary for the normal development of the prostate gland as well as the normal growth and hyperplasia of the prostate.

**Table 2: AUA Nomenclature Linking Statement Type to Level of Certainty, Magnitude of Benefit or Risk/Burden, and Body of Evidence Strength**

[![](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Table%202.PNG)](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Table%202.PNG)

BPH is nearly ubiquitous in the aging male with worldwide autopsy proven histological prevalence increases starting at age 40-45 years to reach 60% at age 60 and 80% at age 80.9 While BPH, or histological hyperplasia, in and of itself does not require treatment and is not the target of therapeutic intervention, it can lead to an enlargement of the prostate called benign prostatic enlargement (BPE). The onset of the enlargement is highly variable as is the growth rate,10 and not all men with BPH will develop any evidence of BPE. The prostate gland may eventually cause obstruction at the level of the bladder neck, which in turn is termed benign prostatic obstruction (BPO), assuming a non-cancerous anatomy. It is important to realize that not all men with BPE will develop obstruction or BPO, just as not all men with BPH will have BPE. To complicate matters further, obstruction may also be caused by other conditions referred to as BOO. Thus, BPO is a subset of BOO.

Parallel to these anatomical and functional processes, LUTS increase in frequency and severity with age and are divided into those associated with storage of urine, and/or with voiding or emptying. Male LUTS may be caused by a variety of conditions, which include BPE and BPO. The enlarged gland has been proposed to contribute to the male LUTS complex via at least two routes: 1. Direct BOO/BPO from enlarged tissue (static component); and 2. Increased smooth muscle tone and resistance within the enlarged gland (dynamic component). This complex of storage symptoms is often referred to as overactive bladder (OAB). In men, OAB may be the result of primary detrusor over activity (DO)/underactivity, or secondary to the obstruction induced by BPE and BPO.11

It is important to recognize that LUTS are non-specific, occur in men and women with similar frequency and may be caused by many conditions, including BPE and BPO. Histological BPH is common and may lead to BPE. BPE may cause BPO, but not all men with BPH will develop BPE, and not all BPE will cause BPO. Because BPH is nearly ubiquitous and because LUTS in men is commonly associated with and/or caused by BPE/BPO, a compromise terminology is often used referring to "LUTS most likely associated with BPE/BPO and BPH" or "LUTS secondary to BPH." In this Guideline, the Panel refers to "LUTS attributed to BPH" to indicate LUTS among older men for whom an alternative cause is not apparent after a basic evaluation. The Panel acknowledges that with a more extensive evaluation, some of these men will be found to have other conditions causing or contributing to their symptoms. As treatments being considered specifically for BPO become more invasive and risky, the importance of a more definitive diagnosis increases.

#### Supplements and Nutraceuticals

This Guideline does not offer an in-depth discussion of the utility of supplements, nutraceuticals, and herbal preparations. These agents are both widely available and utilized by men suffering from voiding symptoms that they believe may be attributable to an enlarged prostate and remedied by such compounds. There are many studies that have been published in favor of the most common ingredients such as saw palmetto, Pygeum africanum, stinging nettle, zinc, selenium, and others.12 Many such studies suffer from multiple shortcomings (e.g., single center and/or single investigator, short duration, poorly chosen or defined placebo or lack of placebo, lack of placebo run-in period, lack of medication wash out period, unconventional endpoints, lack of intention to treat analysis, responder analysis only).

There are two independently-conducted double-blind, placebo controlled, parallel group trials that were done using a specific extract of the berries of the American dwarf palm tree (saw palmetto), which is the most commonly found ingredient of such supplements.12, 13 Both studies found no benefit over placebo in terms of symptoms, bother, QoL, flowrate recordings, serum PSA, or any other measurable parameter. These two trials, the STEP trial published in 2006 and the CAMUS trial published in 2011,13 point to the of the lack of efficacy in the target population for this Guideline; however, it is noted that formal detailed review beyond these two publications was not conducted for this topic.

#### LUTS

In assessing the burden of disease, the Urologic Diseases in America BPH Project examined the prevalence of moderate-to-severe LUTS reported in U.S. population-based studies that used the definition of an AUA Symptom Index (AUA-SI) score of ≥7.14 Results from the Olmsted County Study showed a progressive increase in the prevalence of moderate-to-severe LUTS, rising to nearly 50% by the eighth decade of life. The presence of moderate-to-severe LUTS was also associated with the development of AUR as a symptom of BPH progression, increasing from an incidence of 6.8 episodes per 1,000 patient years of follow-up in the overall population to a high of 34.7 episodes in men aged 70 and older with moderate-to-severe LUTS. Another study has estimated that 90% of men between 45 and 80 years of age suffer some type of LUTS.15 Although LUTS/BPH is not often a life-threatening condition, the impact of LUTS/BPH on QoL can be significant and should not be underestimated.16 When the effect of BPH-associated LUTS on QoL was studied in a number of community-based populations, the most important motivations for many seeking treatment were the severity and the degree of bother associated with the symptoms. These were also important considerations when assessing BPH and deciding when treatment is indicated.17

#### IPSS versus AUA-SI

The IPSS is a validated, self-administered seven-question symptom frequency and severity assessment questionnaire that was originally developed by the AUA Measurement Committee under the leadership of Dr. Michael Barry and first called the AUA-Symptom Index (AUA-SI).18 IPSS and AUA-SI are identical in terms of questions and answers, administration, and interpretation. This tool is widely available and culturally validated and translated into more than 40 languages. The IPSS is used with a single question on QoL Due to Urinary Symptoms, which is scored separately from the seven IPSS questions:

If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that?

0= Delighted  
1= Pleased  
2= Mostly satisfied  
3= Mixed about equally satisfied and dissatisfied  
4= Mostly dissatisfied  
5= Unhappy  
6= Terrible

#### Treatment Indications

To provide some reference to the clinical efficacy and side effect profile of the procedures discussed in this Guideline, clinical statements are made in comparison to what is generally accepted as the historical standard, that being TURP (monopolar and/or bipolar).

Traditionally, the primary goal of treatment has been to alleviate bothersome LUTS that result from BPO. More recently, treatment has also focused on the prevention of disease progression and complications such as AUR.19 Pharmacologic classes of medications used to treat LUTS/BPH include alpha-adrenergic antagonists (alpha blockers), 5-ARIs, PDE5, and anticholinergics, which may be utilized alone or in combination to take advantage of their different mechanisms of action. An additional class of agent that may be considered in combination with alpha blockers is beta-3 agonists.

There also exist clinical scenarios in which conservative management--including lifestyle changes (e.g., fluid restriction, avoidance of substances with diuretic properties)--or pharmacological management are either inadequate or inappropriate. More recently, long-term use of medications for LUTS/BPH have been implicated in cognitive issues and depression.20 These situations merit consideration of one of the many invasive procedures available for the treatment of LUTS/BPH. Indications for these procedures include a desire by the patient to avoid taking a daily medication, failure of medical therapy to sufficiently ameliorate bothersome LUTS, intolerable pharmaceutical side effects, and/or the following conditions resulting from BPH and for which medical therapy is insufficient: acute and/or chronic renal insufficiency, refractory urinary retention, recurrent UTIs, recurrent bladder stones, and recalcitrant gross hematuria. Acute and chronic adverse events are associated with each class of medical therapy and can include cardiovascular and sexual effects.

Surgical treatment of symptomatic BPH may be classified into three general types: 1. MIST; 2. Simple prostatectomy; and 3. Transurethral surgery. Transurethral surgery involves removal of the obstructing adenomatous tissue via the transurethral route, classically with monopolar electroconductive TURP. A variety of alternatives to the standard monopolar TURP have been developed, including bipolar TURP and various laser-based therapies, to achieve similar clinical efficacy while reducing the risks of perioperative bleeding and short- and long-term complications. In appropriate patients for whom the physical size of the prostate cannot be addressed due to the expertise of the surgeon via a safe or efficacious transurethral approach, simple prostatectomy (i.e., adenoma enucleation) may be considered using an open, laparoscopic or robotic-assisted approach. Finally, in select patients, recent innovations in MIST allow for office-based treatments that obviate the need for regional or general anesthesia, hospital stay, discontinuation of anticoagulation therapy, and surgery.

For this Guideline, the Panel evaluated the commonly used surgical procedures and MISTs to treat LUTS/BPH when indicated based on evaluation by an appropriately trained clinician. These procedures include monopolar and bipolar TURP, robotic simple prostatectomy (retropubic, suprapubic, and laparoscopic), TUIP, bipolar TUVP, PVP, PUL, thermal ablation using TUMT, WVTT, TUNA, enucleation using HoLEP or ThuLEP, RWT, and PAE. Data utilized to generate these statements are based on the results from what the Panel felt were acceptably performed RCTs and CCTs comparing each technique to TURP or SHAM.

#### Index Patient

For this Guideline, the Index Patient** ** is a male aged 45 or older who is consulting a qualified clinician for his LUTS. He does not have a history suggesting non-BPH causes of LUTS, and his LUTS may or may not be associated with an enlarged prostate gland, BOO, or histological BPH.

**Prostate Size and Choice of Surgical Procedure**

The first LUTS Guidelines published by the Agency for Health Care Policy and Research in 1994 recommended against measuring prostate size to guide treatment. Knowledge gained over the past 25 years now allows surgeons to select treatments using a refined approach informed in large part by prostate size and morphology. The Panel recognizes and embraces these important developments and, where possible, provides specific size criteria in statements to inform treatment decisions based on higher-order evidence. Statements without size criteria are those modalities that the Panel concluded are efficacious and safe for a broad range of prostate sizes. In this sense, the Panel also recognizes that the availability of various surgical technologies will vary from one practice setting to another and sought to avoid overly restrictive size criteria.

The Panel also made the following observations with respect to prostate size:

  1. Since the specific gravity of the prostate is 1.05 g/mL, the units gram and milliliter (cc) can be used interchangeably to denote size or volume.21
  2. In the absence of standardized prostate size categories in the literature, the Panel recommends consideration of the following categorical size descriptions when planning treatment: small (< 30 g), average (30-80 g), large (>80 to 150 g), and very large (>150 g). These category suggestions are based on the assumption of surgical expertise with BPH and the Panel opinion; they do not necessarily imply that efficacy in prostates outside the recommended ranges does not exist. The Panel hopes that providers will choose the surgical technique that has the best benefit-to-risk ratio for a specific size range, and, that in cases where that technique is not readily available or where no expertise exist, the patient may be referred to another provider with access and expertise in that technique.
  3. Randomized trials for some devices enrolled men with prostates within specific size ranges. As such, statements for those treatments contain the size ranges most commonly referenced in the currently available and reviewed RCT's included in these Guidelines, and/or as used for FDA approval. However, the Panel recognizes that these devices do not necessarily lack efficacy in prostates below or above the size ranges stipulated in the Statements.



#### Sexual Dysfunction and Surgical Therapy

Data on the sexual side effects of BPH surgery can be difficult to ascertain as many studies are not primarily designed to answer this question. As such, many studies evaluate sexual side effects by looking at reported adverse events only, rather than specifically assessing sexual function. In addition, in some studies, especially those evaluating surgical treatments, patients may not only be undergoing a surgical procedure but are also stopping the previous medical therapy, which can confound interpretation of postoperative sexual function.

Given the strong observed relationship between ED and LUTS/BPH, this group of men is at high risk for sexual dysfunction.22 Patients should be counselled about the sexual side effects of any surgical intervention and should be made aware that surgical treatment can cause EjD and may worsen ED. Interventions for LUTS/BPH have clear sexual side effects and tthese treatments have a significant rate of EjD. Libido does not appear to be affected significantly by surgical therapy, and some studies have even shown an improvement in erectile function (EF) after surgical treatment ((this improvement is controversial as other studies show a worsening of EF).19 Most importantly, sexual side effects from surgical treatments are more likely to be permanent than those from medical treatments, which can often be reversed by stopping medical treatment or switching to an alternative treatment.

#### Shared Decision-Making

It is the hope that this clinical Guideline will provide a useful reference on the effective evidence-based management of male LUTS/BPH utilizing standard surgical techniques, MISTs using newer technologies, and treatments the Panel feels are investigative. This Guideline also reviews a number of important aspects of the evaluation of LUTS, including available diagnostic tests to identify the underlying pathophysiology and to better assist in identifying appropriate candidates for invasive treatments. Certain treatment modalities recommended in the Guideline may be unavailable to some clinicians, for example due to lack of access to the necessary equipment/technology or a lack of expertise in the use of such modalities. In such instances, clinicians should discuss the key treatment classes with patients and engage in a shared decision-making approach to reach a treatment choice, which may necessitate a referral to another clinician for the chosen treatment. In all instances, patients should be provided with the risk/benefit profile for all treatment options in light of their circumstances to allow them to make informed decisions regarding their treatment plans.

#### Legacy Technologies

The panel recognizes that there has been a dramatic evolution in the operative techniques available for LUTS/BPH. The panel recognizes that there are some "legacy technologies" that have been historically used, and are currently FDA approved, but have very limited newly published data to be able to comment on their efficacy. The panel has observed that with newer minimally invasive technologies these "legacy technologies" are largely being displaced. The panel recognizes transurethral microwave thermotherapy of the prostate (TUMT) and transurethral needle ablation of the prostate (TUNA) as two of these legacy technologies, therefore guideline statement referencing these "legacy technologies" have been removed.

###  GUIDELINE STATEMENTS 

### Evaluation

#### Initial Evaluation

####  Guideline Statement 1 

******In the initial evaluation of patients presenting with bothersome LUTS possibly attributed to BPH, clinicians should obtain a medical history, conduct a physical examination, utilize the International Prostate Symptom Score (IPSS), and perform a urinalysis. (_Clinical Principle_)**

Discussion

×

#### Discussion

Patients with bothersome LUTS may present to either a primary care provider or urologist. A complete medical history should be taken to assess patient symptoms, prior procedures that could explain presence of symptoms, sexual history, use of medications, and overall fitness and health. The IPSS, a validated self-administered questionnaire, can provide clinicians with information regarding the symptom burden patients are experiencing. Additionally, while a urinalysis cannot diagnose BPH, it can help clinicians to rule out other causes of LUTS not associated with BPH through the detection of bacteria, blood, white cells, glucose, or protein in the urine. When interpreting the results of the urinalysis, clinicians should focus on the presence or absence of glucosuria, proteinuria, hematuria, and infection.

Optional studies that may be used to confirm the diagnosis or evaluate the presence and severity of BPH include PVR, uroflowmetry, and pressure flow studies. A PVR can be useful in determining a baseline ability of the bladder to empty, detecting severe urinary retention that may not be amenable to medical therapy, and/or indicate detrusor dysfunction. There is no universally accepted definition of a clinically significant residual urine volume and following a trend over time is the best way to use this tool.

Uroflowmetry is a simple and risk-free, office-based procedure that can be an important adjunct in the evaluation of LUTS. Flow rates of <10 mL/s have shown a specificity of 70%, a positive predictive value of 70%, and a sensitivity of 47% for BOO.23 If the patient's condition is not sufficiently suggestive of obstruction (e.g., peak urinary flow [Qmax] >10 mL/sec), pressure flow studies should be considered as treatment failure rates are somewhat higher in the absence of obstruction. If interventional therapy is planned without clear evidence of the presence of obstruction, the patient needs to be informed of potentially higher failure rates of the procedure.

Following initial evaluation, clinicians and patients should utilize a shared decision-making approach to determine the need for and type of therapy. This decision will guide the need for further evaluation should the patient desire treatment.

Close

* * *

####  Guideline Statement 2 

******Patients should be counselled on options for intervention, which can include behavioral/lifestyle modifications, medical therapy and/or referral for discussion of procedural options. (_Expert Opinion_) **

Discussion

×

#### Discussion

Lifestyle and behavioral interventions are reasonable first-line treatments for all patients. Straightforward interventions include limiting intake of the following: fluids prior to bedtime or travel**;** mild diuretics, such as caffeine and alcohol; and bladder irritants, such as highly seasoned or irritative foods. Other interventions include avoiding constipation, increasing physical activity, weight loss, Kegel exercises at time of urinary urgency, timed voiding regimens, and double-voiding techniques.24 Pelvic floor muscle training, including biofeedback, may be helpful for patients with urgency and storage symptoms.25

For those patients with bothersome LUTS in whom additional therapy is warranted, it is appropriate to discuss medical therapy. The potential benefits and harms of proceeding to a procedural intervention without trialing medications may also be discussed as part of the informed decision-making process. As primary care providers may not feel comfortable discussing procedural interventions, offering referral to a specialist without a trial of medication is reasonable.

Close

* * *

####  Follow-Up Evaluation 

#### Guideline Statement 3

**Patients should be evaluated by their providers 4-12 weeks after initiating treatment (provided adverse events do not require earlier consultation) to assess response to therapy. Revaluation should include the IPSS. Further evaluation may include a post-void residual (PVR) and uroflowmetry. (_Clinical Principle_)**

Discussion

×

#### Discussion

Recommendations for follow-up after initiating medical therapy for bothersome LUTS/BPH remain undefined. Time intervals, tests to be conducted, and consequences of changes in parameters such as the IPSS, QoL score, flowrate recordings, or residual urine volume have not been systematically studied in the literature.

For shorter duration of onset drugs such as alpha blockers, beta-3 agonists, PDE5s and anticholinergics the first follow-up visit can be as early as four weeks. For longer acting drugs such as 5-ARIs, the first follow-up visit may be within three to six months if adverse events do not necessitate an earlier visit.

During the follow-up visits, patients should be queried regarding the occurrence of typical adverse events of the medication taken, the IPSS and QoL score should be re-administered, and uroflowmetry and residual urine determination is advised.

There are no thresholds in the literature for monitoring changes in PVR to help guide therapy. However, increasing amounts of residual urine with worsening voiding efficiency over time may indicate the need for more frequent follow-up visits and prompt additional investigations such as pressure flow studies, cystoscopy and prostate volume assessment, and/or a change in therapy.

There are no thresholds in the literature for monitoring changes in Qmax to help guide therapy. On average, an improvement between 1 and 5 mL/s may be expected, while other patients may experience no changes or even a minor deterioration. Patients may not notice such subtle changes and they are not, in general, correlated to changes in the IPSS or the QoL score.

There are no thresholds in the literature for monitoring changes in the IPSS/QoL to help guide therapy. However, directional changes can be used as a springboard to a meaningful discussion of patients' expectations of symptom improvement, perceived response to treatment, and goals of treatment.

After some time on treatment, several studies asked patients Global Subjective Assessment (GSA) questions to assess subjective responses to therapy. The responses were then correlated to the changes in the IPSS score at the same follow-up visit and analyzed.26, 27

How satisfied are you with the improvement in your urination symptom following the treatment?

  * very satisfied /happy /pleased
  * somewhat satisfied/ pleased/ happy
  * neither satisfied/ pleased /happy nor unsatisfied/ displeased/ unhappy
  * somewhat unsatisfied/ displeased/ unhappy
  * very unsatisfied/ displeased/unhappy



While substantial differences may exist among individual patients in terms of treatment expectations, perceptions of the overall IPSS, and treatment satisfaction, generalizable observations are as follows:

  * There is a direct correlation between the direction of the IPSS and the GSA response (e.g., an improvement in one is typically matched with an improvement in the other).
  * Large magnitude changes in the IPSS correspond to smaller magnitude changes in QoL (e.g., on average, a larger IPSS point improvement is required to achieve a relatively small improvement in QoL).
  * The baseline IPSS score predicates the change in IPSS needed to achieve threshold improvements in IPSS and GSA: the greater the baseline IPSS score, the more of a drop is required to achieve improvements in GSA. This relationship between baseline IPSS and required drop in IPSS is linear and unique for each threshold of improvement elicited by the GSA question.



Barry et al. showed this relationship for the first time by correlating responses to a GSA at 13 weeks after treatment initiation in the VA Cooperative Study #405 that randomized 1,218 men to 4 different therapies (placebo, terazosin, finasteride, terazosin and finasteride combination) over 12 months.26 Table 2 shows that, on average, a -3 point decrease is needed for a 'slight' improvement and a -5.1 and -8.8 point improvement for a 'moderate' or 'marked' improvement. However, depending on whether the patients were moderately or severely symptomatic at baseline, the decrease required to achieve the threshold improvements differed substantially (**Table 3**).

Roehrborn et al. performed a similar analysis using a 7-point Likert scale centered around a neutral response and stratified the patients treated with tamsulosin versus dutasteride versus tamsulosin and dutasteride by baseline symptom score in the CombAT study. The results are substantially similar to those from Barry et al. and are shown in **Table 4** and **Figure 1**.27

The administration of the IPSS is recommended at each time point of follow-up as it enables a conversation about expectations and satisfaction and may lead to changes in treatment. Utilizing a GSA could be considered at follow-up evaluation and further direct conversation.

Uroflowmetry and residual urine measurement may offer warnings for deteriorating detrusor muscle or worsening urodynamic outlet obstruction, thus triggering appropriate further investigations.

A perfect concordance between the IPSS and global assessment should not be expected. If concordance is present, it is reassuring for the provider and patient to continue with therapy or jointly reassess and change to alternative strategies. If concordance is lacking, this offers the opportunity to revisit the patient's priorities and expectations and modify treatment strategies jointly, if indicated.

Therapy should not be continued if patients are neither satisfied nor show a decrease in IPSS.

**Table 3: VA Cooperative Study Showing Relationship Between IPSS and GSA Results**

[![](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Table%203.PNG)](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Table%203.PNG)

**Table 4: Correlation of Patient Perception of Study Medication (PPSM) Responses to Question 11, "Overall how satisfied are you with the study medication and its effect on your urinary problems?" and IPSS:**

[![](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Table%204.PNG)](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Table%204.PNG)

**Figure 1: Correlation of PPSM Responses to Question 11, "Overall how satisfied are you with the study medication and its effect on your urinary problems?" and IPSS:**

[![](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Fig%201.png)](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Fig%201.png)

At follow-up visits, providers may question patients as to their perception of treatment response and offer a similar Likert scale (from very satisfied to very dissatisfied) and contrast that response to the actual change in the IPSS score. This may lead to one of the following scenarios:

![](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Fig%202.png)

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####  Guideline Statement 4 

**Patients with bothersome LUTS/BPH who elect initial medical management and do   not have symptom improvement and/or experience intolerable side effects should undergo further evaluation and consideration of change in medical management or surgical intervention. (_Expert Opinion_)**

Discussion

×

#### Discussion

An initial trial of medical management over 4 weeks with an alpha blocker or PDE5, and over 6-12 months with a 5-ARI is reasonable in men with bothersome LUTS. Referral to a specialist who can offer additional workup and treatment options is recommended for men who either do not improve with medical management, or have symptomatic improvement but intolerable medication-related side effects.

When initial medical management does not lead to symptomatic improvement, the reason for medication failure and the etiology of LUTS should be considered by performance of studies, such as urodynamics, to confirm BOO versus DO. Understanding the contribution of DO versus BOO can aid in patient counseling and in the selection of additional medication options. In men with LUTS predominantly due to BPH, the reason for failure may be related to medication efficacy; as such, procedural or surgical options may be considered. In men with complicated LUTS (potentially not just related to BPH) with a combination of storage and voiding symptoms, failure may be due to the chosen medication effectively treating only a portion of their LUTS; as such, additional medication classes should be considered along with procedural options.

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####  Preoperative Testing 

#### Guideline Statement 5

**Clinicians should consider assessment of prostate size and shape via transrectal or abdominal ultrasound, cystoscopy, or cross-sectional imaging (i.e., magnetic resonance imaging [MRI]/ computed tomography [CT]) if such studies are available, prior to intervention for LUTS/BPH. (_Clinical Principle_)**

Discussion

×

#### Discussion

Since the publication of previous iterations of this Guideline, the approach to the differential diagnosis and the differentiated treatment of male LUTS/BPH has become substantially more sophisticated with prostate size and morphology playing important roles in the decision-making process. For example, intravesical protrusion (e.g., intravesical lobe, ball-valving middle lobe) has been recognized to predict poor outcomes from watchful waiting and most medical therapies.28 Some of the available MISTs are indicated for prostates between specific sizes (i.e. 30 -80g), and some very large prostates should be treated with laser transurethral, open, laparoscopic, or robotically-assisted laparoscopic enucleation. The weight of the prostate gland in grams without the seminal vesicles can be used as an alternative for prostate volume.29

Since DRE is unreliable in estimating prostate size and serum PSA is only a rough indicator, it appears reasonable to recommend prostate imaging, particularly prior to surgical interventions, given that prostate size may direct the clinician as to which intervention to consider.30 Assessment of prostate size and morphology can be achieved by transrectal or abdominal ultrasonography, cystoscopy, or by cross-sectional imaging using CT or MRI. Many patients may have had such imaging as part of the workup for PSA elevation and/or prostate biopsy, or non-urologic conditions that include evaluation of pelvic anatomy; therefore, any such imaging obtained in the recent past preceding the planned surgical intervention may be utilized for size and shape assessment to verify suitability for the therapeutic alternatives under consideration. Imaging obtained within 12 months is preferred; however, given that prostate growth rates are 1.6% per year on average, older imaging can likely give a reasonably accurate estimate of current size if that is all that is available.31 Imaging should provide cross-sectional and sagittal imaging of sufficient resolution to calculate prostate volume and assess presence or absence of an intravesical lobe.32 Prostate size measurements by transrectal or transabdominal ultrasound, or by computerized tomography or other cross-sectional imaging should be done using the volume formula for an ellipsoid body: ellipsoid formula ([height× length× width]×π/6) or ellipsoid formula ([height× length× width]×0.523). For ultrasound measurements it does not matter if the height is measured in the axial or midsagittal image.33

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####  Guideline Statement 6 




**Clinicians should perform a PVR assessment prior to intervention for LUTS/BPH._(Clinical Principle_)**

Discussion

×

#### Discussion

While the evidence base is limited, multiple organizations and their guidelines include PVR measurement as part of the basic evaluation of LUTS. A rising PVR can indicate medication failure and the need for surgical intervention, or further workup may be warranted. While there are no data to indicate the threshold at which an elevated PVR becomes "dangerous," a "large" PVR (>300 mL) is worth monitoring, at the very least. Patients with symptoms from an elevated PVR (i.e., overflow incontinence, bladder stones, UTI, upper tract deterioration), may need to proceed on to surgery or for further urodynamics testing. To fully determine the etiology of an elevated PVR, formal urodynamics testing with a pressure flow study would need to be performed. While a clinically useful test that may drive management choices, PVR does not seem to be a strong predictor of AUR.34

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####  Guideline Statement 7 

**Clinicians should consider uroflowmetry prior to intervention for LUTS/BPH. (_Clinical Principle_)**

Discussion

×

#### Discussion

The generally accepted minimum threshold voided volume for adequate interpretation is 150cc, and patients should be instructed not to Valsalva void. In addition to the flow rate, the shape of the curve and duration of voiding provide useful information as a screening tool for LUTS. These results can help to characterize the voiding dysfunction and are useful in counseling patients regarding surgical outcomes and expectations. Should surgical intervention ultimately occur, comparison of pre- and post-operative flow rates can be very useful in providing objective outcome measurements and determining the impact of therapy on improving obstruction.

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####  Guideline Statement 8 

**Clinicians should consider pressure flow studies prior to intervention for LUTS/BPH when diagnostic uncertainty exists. (_Expert Opinion_)**

Discussion

×

#### Discussion

Pressure flow studies are the most complete means to determine the presence of BOO.35 Non-invasive tools provide useful information, but only pressure flow studies can document detrusor contractility, or lack thereof. Most men with BOO will void with low urinary flow (Qmax < 10 cc/s) at peak voiding pressures and a pressure flow study will confirm BOO if high voiding pressures accompany the low urinary flow.35 Nomograms that combine voiding pressures and maximum urinary flow rate can also be used to better assess probability of the patient having BOO.35 Patients with BOO may have an elevated PVR; however, the correlation between residual volume and degree of obstruction is weak.36

Most patients can be managed and treated surgically without pressure flow studies, as supported by a recent randomized trial comparing routine care to urodynamic testing for LUTS that found a similar rate for progression to surgery (38% versus 36%, total n = 820).37 However, certain circumstances dictate a more complex evaluation. Pressure flow studies can help differentiate urinary retention related to detrusor underactivity, detrusor sphincter dyssynergia, or obstruction due to prostatic enlargement. Urodynamic studies can also categorize LUTS related to DO or low bladder compliance. Treating patients with these underlying conditions for BOO may not lead to meaningful improvement,38 subject patients to unnecessary surgery, and carry increased risks for incontinence and exacerbated voiding symptoms after finishing treatment.

In patients with catheter-dependent urinary retention who may have underactive detrusor function, a pressure flow study is advised; however, clinicians should be aware that there are such patients (e.g., those with bladder diverticulum) in whom studies inaccurately indicate a lack of detrusor contractility.

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####  Guideline Statement 9 

**Clinicians should inform patients of the possibility of treatment failure and the need for additional or secondary treatments when considering surgical and minimally-invasive treatments for LUTS/BPH. (_Clinical Principle_)**

Discussion

×

#### Discussion

The Panel identified several core concepts of treatment failure and retreatment. The Panel recommends consideration of these issues when interpreting outcomes of trials comparing different therapeutic modalities or of trials of a single modality with different lengths of follow-up.

First, treatment failure and retreatment are influenced by the completeness of the procedure and success in addressing obstructive prostatic adenoma, while reported rates of retreatment are influenced by both the duration and the completeness of follow-up. For the methodological analyses of this Guideline, the Panel focused primarily on follow-up duration, a more objective and readily captured metric, and defined durations of post-treatment follow-up as short- (<6 months), intermediate- (6 to 12 months), or longer-term (>12 months). These time intervals were chosen by the Panel prior to the literature search based on the available literature at that time.

Second, the risks of objective (e.g., urinary retention, reduction of flowrate, increasing residual urine, infection) and subjective failure (e.g., worsening of IPSS and/or QoL) increase with longer duration of follow-up.

Third, retreatment may take the form of medical therapy, a minimally invasive intervention, or a surgical procedure.

Fourth, thresholds for and types of retreatments will vary substantially by provider, patient, category of failure (i.e., objective, subjective, or both), and initial treatment modality.

Finally, in contrast to minimally-invasive and newer surgical therapies, (including but not limited to WVTT and PUL), older clinical trials do not consistently report retreatment with medical therapy as an outcome. The difficulty of accurately recording initiation and duration of medical therapy precludes routine assessment. This pattern may lead to underreporting of medical retreatment relative to minimally invasive and surgical retreatments, for which there are clearly definable timepoints at which retreatment takes place.

Indeed, definitions of retreatment or treatment failure have varied considerably across trials, and not all the mentioned categories are standard in BPH studies. The FDA has not issued a standardized definition of retreatment, or requires reporting of retreatment in clinical trials. As a result, individual trial designs employ different definitions. This lack of agreement may potentially lead to misinterpretation of data or bias in assessing retreatment outcomes between different trials and therapies.39 The field of BPH clinical research would benefit from development of an evidence-based and universally employed classification system for retreatment, which would provide urologists and patients with critical and transparent evidence of retreatment risk before determining the best clinical approach.

Despite the variability and limitations stated above, the Panel attempted to provide some evidence of retreatment rates for the majority of the modalities included in this Guideline. The Panel recognizes that this is an area of development/interest to be included in a future amendment.

**TUIP and TURP**

Taylor and Jaffe performed a review of past and contemporary data, including American and European guidelines, and summarized secondary interventions after TURP and TUIP.40 Their review included a study by Lourenco et al. that reported on data from 795 randomized participants across 10 RCTs of moderate to poor quality. Need for a repeat procedure after TUIP was more common than after TURP at 18.4% versus 7.2%.41 Taylor and Jaffe reviewed 29 RCTS that revealed after 8 years, nearly 15% of TURP patients required a secondary procedure.

A more recent RCT (n=86, data reported for 80 completers) conducted in Egypt with 4-year follow-up comparing TUIP to TURP in men with small prostates (≤30g) was identified since last publication.42 Mean age of the participants was 65 years, and the baseline IPSS and prostate size were 19, and 28g, respectively. The long-term need for reoperation was similar between the groups.

Unfortunately, either return to or de novo use of medication is difficult to report and varies considerably by study.

**TUVP:**

There are limited studies available for review of long term retreatment. Six RCTs (n=601) compared effectiveness of TUVP and bipolar TURP, all with followup ≤1 year.43-48 Mean age was 66 years (range 60 to 69), baseline IPSS was 21 (range 18 to 24), and mean prostate volume was 56mL (range 32 to 64). TUVP showed similar need for reoperation (RR: 1.5; 95%CI: 0.6, 3.9). Given the short follow up of these studies, and lack of reporting of medication retreatment in either arms, no conclusions can be made regarding long term efficacy and/or retreatment rates.

**PVP:**

The Greenlight laser has undergone several upgrades since its inception. Men who underwent treatment with the older 80W platform have been shown to have higher rates of retreatment for LUTS/BPH as compared to TURP (RR: 2.0; 95%CI: 1.01, 3.8). In modern surgery most surgeons, if not all, now use higher powered platforms. In the GOLIATH study,49, 50 an international multicenter RCT comparing the higher powered 180W PVP to TURP, 24-month data reported a similar overall need for reoperation (RR: 1.4; 95%CI: 0.6, 3.0) between the two modalities. The Kaplan Meier estimates for reoperation at 24 months were 9.0% for GL-XPS and 7.6% for TURP, which were not statistically different (_p_  = 0.7, log rank test). The breakdown for time period included 19 retreatment surgeries in the first 12 months (10 for GL-XPS patients and 9 for TURP patients); 5 additional cases were identified in the second year - 4 for GL-XPS patients and 1 for TURP. Reasons for reoperation were prostate tissue regrowth/insufficient removal, bladder neck contracture, and urethral stricture.

While the GOLIATH trial excluded patients with prostate volumes > 80g,49 a newer RCT randomized men with prostate sizes of 80-150g (average 105g) to PVP versus TURP versus HOLEP. PVP had a retreatment rate of 26.7% at three years of follow up, which was similar to51-53 that seen with TURP (27.4%). However, both TURP and PVP had statistically higher retreatment rates than men who underwent HoLEP (5%, p=0.03).

Finally, there are several studies utilizing the 80W and 120W lasers with a maximum follow-up of 3 to 5 years. In these studies, redo procedure rates vary from 6.8% to 11% at 3 years, and 8.9% at 5 years of follow-up. Reoperation rates for urethral or bladder neck contractures are reported in 7.4% and 8% in two studies with 3-yr follow-up,51, 52 and in 1.2% of cases in another series with 5-year follow-up.53 Medical therapy with alpha-blockers was seen in 5/84 patients (5.9%), and with anticholinergics in 1/84 (1.2%) at a mean follow-up of 57 months (+/- 6.8 months and 82% of cohort still reporting).

**PUL:**

Based on the L.I.F.T. study, reoperation due to symptom recurrence at 5 years was reported for 19 of 140 participants with 6 receiving additional PUL implants and 13 undergoing TURP or laser procedures.54 Removal of encrusted implants was required in 10 participants, while 3 non-encrusted implants exposed to the bladder were removed prophylactically. Additionally, 15 participants were taking an alpha blocker or 5-ARI at five years.

The prospective, multicenter, randomized, non-blinded BPH6 study provided data comparing 2-year results of PUL compared to TURP.41 A total of 80 patients with LUTS/BPH were assessed for reoperation due to symptom recurrence and there was no significant difference between groups over the 2-year study period (RR: 2.4; 95%CI: 0.5, 11.1).55 Six patients (13.6%) in the PUL arm and two in the TURP arm (5.7%) of the BPH6 Study underwent retreatment for LUTS during the 2-year follow up period. These treatments included additional PUL, intradetrusor botox, laser treatment of the prostate or TURP. Medication retreatment in either arm of the BPH6 study was not reported.

**WVTT:**

One double-blind trial from McVary et al. compared WVTT (135 subjects) with SHAM/control (61 subjects). At the primary double-blind period of three months, only one participant in the thermal therapy group required a reoperation due to LUTS.56-59 At 4 years follow up, the reported retreatment rate had increased to 9.6% (6 subjects underwent procedural interventions, while 7 were on medical therapy). This reported rate was calculated based on the original 135 subjects, however, attrition yielded only 90 available for assessment. Therefore, the reintervention rate may be higher.60

**Laser Enucleation:**

Recurrence of symptoms or need for reoperation were reported in 5 studies comparing HoLEP to TURP. One of these studies reported no events.61 Pooled analysis with the 4 remaining studies resulted in no differences (RR: 0.42; 95%CI: 0.07, 2.48].62, 63 Other adverse events, including urethral stricture and bladder neck contracture, were similar for the HoLEP and TURP groups. Similarly, few patients required reoperation following ThuLEP and TURP. Pooled analysis from 3 studies found that the groups were similar (RR: 1.3; 95%CI: 0.2, 11.3).64-66

The Zhang diode laser study reported urethral stricture occurrence in 1 participant (1%) in the diode laser group and 2 participants (3%) in the TURP group.67 There were no reported cases of bladder neck contracture.

One trial reported need for retreatment at 3 years due to recurrence of BOO symptoms, where retreatment included the use of medications such as alpha blockers, or surgery.53 This study reported significantly higher retreatment rates in the TURP group compared to HoLEP group, 27.4% versus 5% (P=0.03). Other adverse events, including urethral stricture and bladder neck contracture, are similar for the HoLEP and TURP groups in the studies in which this was reported.

In pooled data from 11 ThuLEP studies, few patients required reoperation. Pooled analysis from 3 studies found the thulium laser and TURP groups had similar reoperation rates (RR: 1.3; 95%CI: 0.2, 11.3). Stress incontinence, reported in 4 studies, was similar for the thulium and TURP groups (RR: 0.46; 95%CI: 0.14, 1.56). Other post-surgical complications (e.g., urethral stricture, urge incontinence, urinary retention, UTI) were similar between groups.

**RWT:**

The one-year outcome data from the Gilling study revealed one participant in the TURP group (2%) and 3 in the RWT group (3%) required surgical retreatment for BPH (RR: 1.68; 95%CI: 0.17, 15.83).68 At 36 months, one participant in the TURP group (1.5%) and 5 in the RWT group (4.3%) required surgical retreatment for BPH (RR: 2.80; 95%CI: 0.33, 23.47). All re-operations were done within the first 20 months after initial surgery.69 The authors reported the occurrence of medical failure at 36 months follow-up (defined as needing to start alpha blockers or 5-ARI anew) in 9% of participants after RWT, and 14% of participants after TURP.51

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###  Medical Therapy 

#### Alpha Blockers

####  Guideline Statement 10 

******Clinicians should offer one of the following alpha blockers as a treatment option for patients with bothersome, moderate to severe LUTS/BPH: alfuzosin, doxazosin, silodosin, tamsulosin, or terazosin. (_Moderate Recommendation; Evidence Level: Grade A_)**

Discussion

×

#### Discussion

Multiple phase III RCTs, Phase IV studies, systematic reviews, and meta-analyses have demonstrated the efficacy of alpha blockers for the treatment of LUTS and BPH since the first drugs in the class (terazosin and doxazosin) were introduced in the 1980 and 1990s, respectively, for this indication. There is nearly universal agreement that they are all relatively equally effective in terms of IPSS improvement, with an expected range of improvement of 5-8 points, compared to an expected effect of placebo from 2-4 points.70, 71 One of the most recent exhaustive network meta-analyses verifies this observation (**Table 5**).70

Studies have attempted to discern efficacy differences between different alpha blockers and to identify subgroups of patients who may respond better to one alpha blocker or another. These data, by and large, have demonstrated equal efficacy across all alpha blockers, with no particular subset of patients more or less suited for such treatment.72 Due to the similar efficacy and efficiency, it is not recommended to switch between different alpha blockers if patients fail to have sufficient improvement with the first drug, using an appropriate dosage, as it will unlikely succeed in improving the response. Rather, providers are encouraged during follow-up to reassess and discuss alternative treatment strategies or to further investigate the phenotype of the patient (e.g., rule out overly large prostate or presence of intravesical/middle lobe).70 However, changing from one alpha blocker to another on the basis of a side effect is worthwhile.

**Table 5: Effectiveness of Drug Therapies in Improving IPSS**

[![](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Table%205.png)](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Table%205.png)

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####  Guideline Statement 11 

**When prescribing an alpha blocker for the treatment of LUTS/BPH, the choice of alpha blocker should be based on patient age and comorbidities, and different adverse event profiles (e.g.,** **ejaculatory dysfunction [EjD], changes in blood pressure). (_Moderate Recommendation; Evidence Level: Grade A_) **

Discussion

×

#### Discussion

Given the similar efficacy of the approved alpha-1-adregergic antagonists, the choice of specific agent should consider the differing adverse events profiles of each.

The quinalozin derivatives, terazosin and doxazosin, are non-specific alpha-1 receptor blockers that are both approved for the treatment of hypertension, as well as BPH. Tamsulosin, alfuzosin, and silodosin have lower potential to cause orthostatic hypotension and syncope than either terazosin or doxazosin.73-75 Tamsulosin may further have slightly less effect on blood pressure than alfuzosin.71 These differential effects on blood pressure by different alpha-1-antagonists may be due to their differential blocking of alpha-1 adrenoceptor subtype selectivity.76 The only two alpha blockers with selectivity for the alpha 1a versus the alpha 1b receptor are tamsulosin (10:1) and silodosin (161:1).

The hypotensive effects of terazosin and doxazosin can be potentiated by concomitant use of a PDE5, such as sildenafil or vardenafil. Tamsulosin at a dose of 0.4 mg/day, however, does not appear to significantly potentiate the hypotensive effects of sildenafil.77 Regardless, patients utilizing both these medications should be counselled appropriately regarding the risk for drops in blood pressure and symptoms associated with this.

It has long been understood that alpha-adrenergic receptor blockade may induce EjD. This also appears to be a reflection of the selectivity, and those drugs more selective for the alpha 1a versus the alpha 1b receptor are more prone to induce EjD (i.e., tamsulosin, silodosin).

In a recent comprehensive meta-analysis, Gacci et al.78 reported that EjD events were significantly more common with alpha blockers than with placebo (7.7% versus 1.1%; OR: 5.88; _P_ < 0.0001). Stratifying according to the drug used, EjD was significantly more prevalent with tamsulosin (OR: 8.57; _P_ = 0.006) or silodosin (OR: 32.5; _P_ < 0.0001) than placebo, while doxazosin (OR: 0.80; _P_ = 0.14) and terazosin (OR: 1.78; _P_ = 0.71) were associated with a low risk of EjD, similar to placebo. Data for about 1,400 patients from 4 RCTs compared silodosin and tamsulosin. Overall, tamsulosin was associated with a significantly lower risk of EjD than silodosin (OR: 0.09; P < 0.00001). These findings are in line with the alpha 1a selectivity over the alpha 1b receptor of tamsulosin (10:1) and silodosin (161:1).****

**Table 6: Silodosin, Ejaculatory Dysfunction, and Medication Discontinuation by Age 80, 81**

[![](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Table%206.PNG)](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Table%206.PNG)

For many years, EjD was referred to as retrograde ejaculation (RE), which is commonly found after TURP and surgeries affecting the anatomy of the bladder neck and prostate. However, Hellstrom demonstrated that the EjD associated with selective alpha 1a blockers is correctly called "anejaculation" and found that tamsulosin resulted in significantly decreased ejaculate volume (-2.4 +/- 0.17 mL) compared to alfuzosin (+0.3 +/- 0.18 mL; p < 0.0001 versus tamsulosin) or placebo (+0.4 +/- 0.18 mL; p < 0.0001 versus tamsulosin; p = nonsignificant versus alfuzosin).79 Despite the difference in ejaculate volume, no significant differences were observed in post-ejaculate urine sperm concentrations between tamsulosin, alfuzosin, and placebo groups (1.6 ± 0.87, 1.3 ± 0.87 and 0.9 ± 0.88 million/mL, respectively). These data demonstrate that the phenomenon is anejaculation due to paralysis of the smooth muscles in the wall of the prostatic ducts and ejaculatory ducts rather than RE.

Anejaculation is noted by patients and may lead to dissatisfaction and treatment discontinuation. In the phase III silodosin studies, it was noted that the number of men reporting EjD as an adverse event decreased from 46% to 11% for men in their 50s versus 70s, respectively, and the number of men discontinuing treatment due to the adverse events decreased from 4.7% to 0 %.80, 81

Based on these examples, it is reasonable to select alpha blockers with equal efficacy based on expected adverse events. Younger sexually active men are more likely to discontinue due to EjD; therefore, it would be prudent to select alpha blockers with a low incidence of EjD.

When treating patients on several antihypertensives, or with orthostatic hypotension, it is best to select an alpha blocker that exhibits minimal impact on blood pressure (e.g., the highly selective alpha 1a blocker silodosin).

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####  Alpha Blockers and Intraoperative Floppy Iris Syndrome (IFIS) 

#### Guideline Statement 12

**When initiating alpha blocker therapy, patients with planned cataract surgery should be informed of the associated risks and be advised to discuss these risks with their ophthalmologists. (_Expert Opinion_)**

Discussion

×

#### Discussion

IFIS was first described by Chang and Campbell in 2005 as a triad of progressive intraoperative miosis despite preoperative dilation, billowing of a flaccid iris, and iris prolapse toward the incision site during phacoemusification for cataracts.82 Operative complications in some cases included posterior capsule rupture with vitreous loss and postoperative intraocular pressure spikes, though visual acuity outcomes appeared preserved. The original report linked this condition with the preoperative use of tamsulosin; iris dilator smooth muscle inhibition has been suggested as a potential mechanism.82, 83 A meta-analysis revealed tamsulosin carried the highest risk for IFIS (40x that of alfusozin), but all alpha blockers increase the risk of IFIS to some degree.84 One study revealed that for every 255 men receiving tamsulosin in the immediate preoperative cataract surgical period, one serious complication (e.g., retinal detachment, lost lens or lens fragment, endophthalmitis) would result.85 Discontinuation of tamsulosin 4 to 7 days prior to cataract surgery is routine practice, but it does not completely eliminate IFIS risk.86

Urologists initiating alpha blocker therapy should inquire about the presence of cataracts or plans for future cataract surgery. Urologists should inform identified patients with planned cataract surgery of IFIS risk and delay initiation of alpha blocker therapy until after the procedure. Increased awareness of IFIS has resulted in a year by year decreased complication rate.87 In a shared decision-making model, the ideal scenario includes a patient, urologist, and ophthalmologist all well informed about IFIS and cataract surgery risk. Ultimately, ophthalmologists performing the cataract surgery are responsible for taking a detailed medication history and initiating a prevention and mitigation strategy for IFIS-related complications. In addition to alpha blockers, several other non-urologic drugs, including benzodiazepines, donepezil and duloxetine, have been associated with IFIS. Even in verified high-risk IFIS patients, ophthalmologists can decrease complication rates to baseline through a variety of mitigation strategies.88-90

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####  5-Alpha Reductase Inhibitor (5-ARI) 

#### Guideline Statement 13

**For the purpose of symptom improvement, 5-ARI monotherapy should be used as a treatment option in patients with LUTS/BPH with prostatic enlargement as judged by a prostate volume of > 30g on imaging, a prostate specific antigen (PSA) > 1.5ng/mL, or palpable prostate enlargement on digital rectal exam (DRE). (_Moderate Recommendation; Evidence Level: Grade B_)**

Discussion

×

#### Discussion

While there are several medical and surgical ways to reduce the influence of androgenic steroids on the growth of the prostate (e.g., medical or surgical castration), the only hormonal therapies with an acceptable benefit-to-RR are the 5-ARIs. Both testosterone and DHT bind to the androgen receptor, although DHT does so with greater affinity and is thus considered to be the more potent androgenic steroid hormone. This conversion is enabled by the enzyme 5AR, of which there are two isoenzymes, known as type I and type II.

The T/DHT-androgen receptor complex within the nucleus of the cells of the prostate initiates transcription and translation, thus promoting cellular growth. BPH develops due to an imbalance between growth and apoptosis (cellular death) in favor of growth, subsequently causing an increase in cellular mass.91, 92

5-ARIs act via inhibition of 5AR, leading to less available DHT in the prostate. This, in turn, leads to a reduction in the overall androgenic growth stimulus in the prostate, an increase in apoptosis and atrophy, and ultimately a shrinkage of the organ ranging from 15-25% measured at six months. The atrophy is most pronounced in the glandular epithelial component of the prostate, which is the source of the production and release of serum PSA. It is for this reason that organ shrinkage is associated with a reduction in serum PSA by approximately 50% (and a concomitant decrease in serum free PSA by 50%, which means that the ratio of free/total PSA remains constant).93, 94 Therefore, when providers are monitoring men who are on 5-ARIs, the measured serum value of the PSA should be doubled to accurately gauge disease progression and prostate cancer screening.

As the indication for treatment with 5-ARIs and combination therapy hinges on prostate volume and PSA threshold, the treating physician should discuss the relationship between PSA and prostate size/volume with the patient. Overall, the larger the gland, the greater the reduction in prostate volume with 5ARI therapy.95, 96 While the accepted historic threshold for significant improvement with 5ARI therapy has been 40 cc95, several very large studies defined enrollment at >30g and achieved significant results, therefore reducing the threshold volume. Obtaining imaging with TRUS (or reviewing existing cross-sectional imaging) to assess prostate size more objectively is reasonable for overall management, and its role when considering procedures is further discussed in the Evaluation section of this Guideline. A palpably enlarged prostate on DRE may also qualify men for 5-ARI treatment, but providers should be aware of the frequent inaccuracy of size determination by DRE.30 While serum PSA is helpful in assessing treatment options (primarily as a surrogate for prostate size), providers do not need to obtain a PSA solely for determination of 5-ARI response, however, a minimum threshold PSA .1.5ng/mL is advised when initiating 5ARI therapy. PSA screening should be undertaken in age-appropriate men as part of shared medical decision-making for prostate cancer screening. The compounds in this class approved for the treatment of BPH, finasteride at a dose of 5 mg daily and dutasteride at a dose of 0.5 mg tablet daily, differ in two important pharmacological characteristics.97-99 Finasteride exclusively inhibits the 5-AR type II isoenzyme, while dutasteride inhibits both types I and II. This difference in activity leads to a reduction in serum levels of DHT by approximately 70% with finasteride, compared to approximately 95% with dutasteride.98 However, in the prostate, and specifically in BPH tissue, type II 5-AR is far more common than type I.91 Therefore, the reduction of DHT in prostate tissues relative to placebo is less pronounced and has been measured at approximately 80% (finasteride)100 and approximately 94% (dutasteride).101 The serum half-life of finasteride ranges from six to eight hours, whereas that of dutasteride is five weeks. This pharmacokinetic difference may have implications in terms of treatment compliance, as well as persistence of side effects.102

Due to the slow onset of action of this class of medications, other medication classes (principally alpha blockers) may lead to more immediate relief for men with voiding symptoms. Patients should be counseled on a slower improvement in symptoms if men are treated with 5-ARI alone.

**Finasteride**

Numerous robust analyses of randomized, placebo-controlled trials have shown an improvement in standardized symptom scores (e.g., IPSS) superior to placebo. Numerically, improvements of 3 to 4 points were observed and maintained for 6 to 10 years of follow-up.103, 104 The magnitude of improvement was similar when patients were stratified by prostate volume or serum PSA. However, the natural history of symptomatic disease progression is more accelerated in men with larger glands and higher serum PSA values; correspondingly, the outcomes between finasteride and placebo groups become more accentuated in men with larger glands over time.105-107

**Dutasteride**

Dutasteride is the second 5-ARI approved by the U.S. Food and Drug Administration (FDA) for the use in men with LUTS and BPH.108 Initial phase-3 randomized studies demonstrated the efficacy of dutasteride and were reviewed along with the 2 year CombAT trial data.109-111 Roehrborn and colleagues (2002) randomized 4,325 men with BPH and moderate to severe symptoms to dutasteride 0.5 mg daily or to placebo and followed them for 24 months.109 These data are pooled from three identical phase-three clinical trials, encompassing 400 sites in the United States and 19 other countries. AUA-SI improved significantly in both treatment groups (p<0.001), with significantly greater improvement with dutasteride (-4.5) compared with placebo (-2.3) (p<0.001).

During the last decade, additional data from REDUCE have become available, along with two new RCTs. REDUCE's primary endpoint was to look at biopsy proven prostate cancer in men on placebo or 5-ARI. While original study inclusion criteria were PSA 2.5-10ng/mL, prostate volume ≤80g and IPSS <25, the post hoc analysis looked at men with IPSS<8 and prostate volumes 40-80g with particular interest in clinical progression of men with enlarged prostates, but mild LUTS symptoms attributed to BOO. Clinical progression (as defined by increase in IPSS of ≥4, AUR, UTI, or BPH-related surgery) was less common in men on dutasteride compared to placebo (21% versus 36%; p<0.001). When assessing for absolute risk reduction for men on dutasteride compared to placebo, there were noticeable differences both with AUR (6% risk reduction) and BPH-related surgery (3.8%).112

Only one study has directly compared the outcomes of men randomized to either finasteride or dutasteride. Amongst men randomized to either medication over 12 months, no differences were noted with regards to prostate volume, AUA-SI and Qmax.113 Indirect comparisons of efficacy between finasteride and dutasteride are limited in that only patients with baseline prostate volumes > 30g by TRUS and serum PSA levels > 1.5 ng/mL were eligible for enrollment in dutasteride clinical trials, thus enriching the population for potential responders to 5-ARI treatment when compared to finasteride trials with less selective populations.

**5-ARIs and Prostate Cancer**

The Panel agreed that it is important to share the following observations regarding the use of 5-ARIs and prostate cancer prevention, risk reduction, the risk of high-grade disease, and the danger of not paying attention to the expected 50% reduction in PSA under 5-ARI treatment.

The PCPT trial randomized 18,000 men with a PSA <3 to finasteride versus placebo; biopsy was performed if PSA >4 or abnormal DRE, and an end of study per protocol biopsy was performed in all participants. There was a significant reduction in the period prevalence of prostate cancer resulting in a relative risk reduction of 25%, with 18.4 % of the finasteride group and 24.4 % of controls being diagnosed with cancer. High-grade cancer was more frequent in the finasteride group (6.4% versus 5.1%).114

The REDUCE trial enrolled 8,000 men with a PSA 2.5-10, negative biopsy within 6 months of enrollment, and a planned per protocol biopsy at years 2 and 4. Relative risk reduction of the period prevalence of prostate cancer was 23%, with 25.1% in control group versus 19.9% in dutasteride group being diagnosed. High-grade cancer (Gleason score sum 8) was more common in the dutasteride group (0.36% versus 0.03%).115

CombAT was a 4-year randomized double-blind parallel group study in 4,844 men ≥50 years of age with clinically diagnosed moderate to severe BPH, IPSS ≥12, prostate volume ≥30 mL, and serum PSA 1.5-10 ng/mL. Participants underwent annual PSA measurement and DRE, and prostate biopsies were performed for cause, only. In this sense, the CombAT trial is the only study that followed BPH patients as would be done in routine practice without per protocol biopsies, instead performing only clinically indicated biopsies based on PSA and/or DRE findings. Dutasteride (alone or in combination with tamsulosin) was associated with a substantially greater relative risk rate for prostate cancer diagnosis of 44% compared with tamsulosin monotherapy (95%CI: 16%, 57%; _p_  = 0.002), and a 40% reduction in the likelihood of biopsy. There were similar reductions in low- and high-grade Gleason score cancers. The biopsy rate in the groups receiving dutasteride trended toward a higher diagnostic yield (combination: 29%, dutasteride: 28%, tamsulosin: 24%). **(Figure 2)** 116

Number of prostate cancer cases and Gleason score distribution by treatment group and time period. Numbers above bars indicate total number of cancers detected by treatment group; numbers within bars report occurrence by Gleason score.

Lastly, Sarkar et al.117 published a population-based cohort study linking the Veterans Affairs Informatics and Computing Infrastructure with the National Death Index to obtain patient records for 80,875 men with American Joint Committee on Cancer stage I-IV prostate cancer diagnosed from January 1, 2001, to December 31, 2015. The primary outcome was prostate cancer-specific mortality (PCSM). Secondary outcomes included time from first elevated PSA (defined as PSA≥4 ng/mL) to diagnostic prostate biopsy, cancer grade and stage at time of diagnosis, and all-cause mortality (ACM). PSA levels for 5-ARI users were adjusted by doubling the value, consistent with previous clinical trials. Median adjusted PSA at time of biopsy was significantly higher for 5-ARI users than 5-ARI non-users (13.5 ng/mL versus 6.4 ng/mL; P <.001). Patients treated with 5-ARIs were more likely to have Gleason grade 8 or higher (25.2% versus 17.0%; P <.001), clinical stage T3 or higher (4.7% versus 2.9%; P <.001), node-positive (3.0% versus 1.7%; P <.001), and metastatic (6.7% versus 2.9%; P <.001) disease than 5-ARI non-users. In a multivariable regression, patients who took 5-ARIs had higher prostate cancer-specific (subdistribution hazard ratio [SHR]: 1.39; 95%CI: 1.27, 1.52; P <.001) and all-cause (HR: 1.10; 95%CI: 1.05, 1.15; P <.001) mortality. This study demonstrates that prediagnostic use of 5-ARIs was associated with delayed diagnosis and worse cancer-specific outcomes in men with prostate cancer and highlights a continued need to raise awareness of 5-ARI-induced PSA suppression and appropriate correction (i.e., a multiplication of the PSA value under 5-ARIs x 2).

**Figure 2: Gleason Score of Prostate Cancer Diagnosed in the CombAT Study**

[![](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Fig%202.jpg)](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Fig%202.jpg)

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####  Guideline Statement 14 

**5-ARIs alone or in combination with alpha blockers are recommended as a treatment option to prevent progression of LUTS/BPH and/or reduce the risks of urinary retention and need for future prostate-related surgery. (_Strong Recommendation; Evidence Level: Grade A_)**

Discussion

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#### Discussion

The Proscar Long-Term Efficacy and Safety Study (PLESS) trial was a large clinical study to investigate the effects of finasteride on the management of BPH.118 In this multicenter, double-blind, placebo-controlled study conducted in the United States, more than 3,000 men with moderate to severe LUTS and an enlarged prostate on DRE were randomized to a finasteride group, 5 mg/day, or a placebo group. During the 4-year study period, 10% of the 1,516 men in the placebo group and 5% of the 1,524 men in the finasteride group underwent surgery for BPH (a 55% reduction in risk with the use of finasteride). AUR developed in approximately 7% of the men in the placebo group and approximately 3% of the men in the finasteride group (a 57% reduction in risk with the use of finasteride). There was a significant (p<0.001) decrease in the mean IPSS, with a 3.3-fold reduction in the finasteride group and a 1.3 reduction in the placebo group. Treatment with finasteride improved urinary flow rates and significantly (p<0.001) reduced prostate volume.

LUTS/BPH can have a progressive natural history that is more profound in men with larger glands and/or higher PSA values. Men with these risk factors for progression who undergo conservative treatment (watchful waiting or placebo groups) face an increasingly worse prognosis due to a more rapid disease progression with unchecked continued prostate growth. The PLESS study suggests that long-term medical therapy could impact the natural history of BPH as manifested by AUR and surgery. As such, a 5-ARI could be utilized in appropriately enlarged prostates as prevention for BPH since it may alter the natural history thereof. Men with larger prostate glands and lower urinary flow rates appear to benefit most from treatment with finasteride. Amongst men randomized to 5-ARI instead of alpha blocker alone or placebo groups, there is a lower risk of AUR and BPH related surgery.96

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####  Guideline Statement 15 

**Before starting a 5-ARI, clinicians should inform patients of the risks of sexual side effects, certain uncommon physical side effects, and the low risk of prostate cancer. (_Moderate Recommendation; Evidence Level: Grade C_)**

Discussion

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#### Discussion

Only three new long-term RTCs have examined the side effects of 5-ARIs since the 2010 Guideline, while a variety of observational and retrospective studies have also examined this topic in that timeframe.112, 115, 119-121

**Sexual Dysfunction**

As part of the Medical Therapy of Prostatic Symptoms (MTOPS) Trial, investigators prospectively measured sexual function, including erectile and ejaculatory function, as well as libido, utilizing questionnaire data.22, 122 Declines in overall sexual function were noted in all arms of the study, including men taking placebo. A small but statistically significant deterioration in ejaculatory function that was above the decline demonstrated in the placebo group was noted for men on finasteride and combination therapy. Men assigned to combination therapy also experienced significant worsening in EF and sexual problem assessment. There was no significant difference in changes in any of the ejaculatory domains among men assigned to doxazosin as compared to placebo.

Previous analyses of randomized, placebo-controlled trials utilizing adverse event reporting outcomes (not questionnaire data) have shown that in the first 6 to 12 months of treatment, patients on finasteride experience ED, libido disturbances, and ejaculatory problems at about twice the rate as the placebo control patients. Thereafter, the rates are often similar, suggesting that age-related deterioration in sexual and ejaculatory function is responsible (rather than direct drug effects) or that the age-related changes in the placebo group equilibrate drug effects. In the PLESS study, sexual adverse events were reported more frequently with finasteride (15%) than placebo (7%) during the first year of the study (p<0.001); however, no between-group difference was noted in the incidence of new sexual adverse events (7% in both groups) during years 2 through 4.123 Study discontinuation due to sexual adverse events occurred in 4% of finasteride patients and 2% with placebo. Amongst men who do experience bothersome ED as an effect of 5-ARI therapy, cessation of drug may allow them to return to the baseline rates of ED.124

Sexually-related adverse events have been examined in a variety of randomized studies with dutasteride groups.112, 115, 119-121 ED rates from the REDUCE trial were 9% versus 5.7% in the placebo group (ARD: 3.2%; 95%CI: 2.1, 4.4).115 At 2-years, the CONDUCT trial reported that the incidence of ED was greater with dutasteride combined with tamsulosin compared with tamsulosin monotherapy at 8% versus 0% (ARD: 8%; 95%CI: 5, 10.7).

Decreased semen volume and decreased or absent libido were also higher in men on dutasteride compared to placebo.112 Ejaculation failure was found to be higher in men on combination dutasteride and 0.2mg tamsulosin compared to 0.2mg tamsulosin, alone (2.6% versus 0.3%; ARD: 2.3%; 95%CI: 0.4, 4.2).120

**Gynecomastia**

The multinational 4-year REDUCE trial115 found an increased incidence of gynecomastia (1.9% versus 1.0%; ARD: 0.8; 95%CI: 0.3, 1.3) with a larger between group difference in the post hoc analysis of a subset of 1,617 men (2.4% versus 0.7%; ARD: 1.7; 95%CI: 0.5, 2.9).112 During the 2-year observational extension phase conducted in 2,751 participants, no new cases of gynecomastia were reported.119 Conversely, a 2-year study conducted in Asia did not demonstrate any increased risk of gynecomastia in men on dutasteride.120 One observational study reported a greater incidence of gynecomastia in men who used finasteride or dutasteride, alone or with an alpha blocker, when compared to non-exposure to LUTS/BPH medications.125 A meta-analysis looking at 14 studies found increased risks of gynecomastia and breast tenderness for men on 5-ARI when compared to placebo.126

**Dementia**

In observational studies, two studies reported on potential risk associated with 5-ARI use.127, 128 One study compared the use of finasteride or dutasteride to men not using either drug.128 Dementia was greater in the finasteride and dutasteride groups as compared to the placebo group in analyses less than 27 months; however, rates were similar after 27 months.128 In the second study, use of 5-ARI was compared to tamsulosin over 20 months with higher rates of dementia seen in the tamsulosin group with a dose-dependent risk noted.112

**Depression**

Two observational studies reported on risks of depression. Rates of depression in men on 5-ARI compared to a non-exposure group demonstrated slightly higher rates that were sustained after 3 years.129 Hagberg et al. utilized both a cohort and case control analysis comparing use of finasteride or dutasteride, alone or with an alpha blocker, to alpha blocker.130 These results contradicted the previous study as they largely demonstrated similar rates of treated depression independent of drug regimen. Other psychological effects, such as increased suicidality and psychological adverse events, have also been examined.20

**Development of Diabetes**

Two observation studies have examined the risk of diabetes to men on 5-ARI; however, these trials have yielded contradictory results.131, 132

**Post-Finasteride Syndrome (PFS)**

PFS is a controversial and poorly-defined constellation of chronic 5-ARI-induced sexual, physical, and psychological symptoms that putatively persist after discontinuation of the 5-ARI.133-136 Concerns regarding PFS prompted the FDA to amend the labels for 5-ARI with a warning of its risks. However, the robustness of the data justifying this change, which is based on anecdotal patient-reported outcomes rather than prospective trials, remains unclear. Dutasteride, which has activity at more 5-ARI receptors than finasteride, has largely not been implicated. In addition, dose response association with finasteride does not seem present as the 1mg dose has been more closely linked to PFS than the more potent 5mg dose.137, 138 The significant increases in reporting after the first published reports of PFS in 2012 (with no signal before 2012) points towards stimulated reporting.20

In general, current data on PFS draw primarily from case reports rather than prospective trials. It is the assessment of the Panel that much of these data are susceptible to bias. For example, many of the studies of male sexual dysfunction on which PFS is based lack baseline (i.e., pre-treatment) assessments of sexual function, a sufficient control population, considerations for perception of medication effects,139 corrections for investigator bias (i.e., investigator awareness of PFS prior to assessment of symptoms), and use of validated sexual health questionnaires. Moreover, retrospective assessments of sexual function may be prone to recall bias.140, 141

Overall, the existence of persistent sexual dysfunction following cessation of 5-ARI is currently not demonstrated by reliable scientific research. First, there are no properly designed studies (e.g., using appropriate controls and addressing the issues described above with respect to the study of sexual function) that report a significant association between discontinuation of finasteride and persistence of sexual dysfunction. Second, if the Bradford-Hill criteria,142 which are used to assess causality, are applied, they do not support an inference of causality. There is neither a strong nor consistent association based upon well-designed, controlled epidemiological studies reported in the literature. The specificity of the outcome (the persistence or onset of new sexual dysfunction) is virtually non-existent given that sexual dysfunction occurs at background rates in all men and not just in men who use 5-ARI's.124, 143 As for biological gradient as one criteria of the Bradford-Hill criteria, it is difficult to understand how 1 mg of finasteride may cause persistence when the 5 mg dose of the same drug is much less likely.137, 138 Additionally, the more broadly acting dutasteride (activity at Type I and II receptors) has been less implicated than the more specific finasteride (activity at Type II receptors only). Finally, the proposed mechanisms for persistence have not been scientifically established and appear implausible in many circumstances as DHT levels return to normal within four weeks after cessation of finasteride use. This implies no persistent effect through a mechanism involving suppressed serum DHT levels.

Epidemiological studies are emerging that adhere to fundamental scientific principles and fail to support the existence of PFS.144, 145 The results of RCT and well-designed, controlled epidemiological studies contain data that do not support the existence of an association between finasteride and persistent sexual dysfunction following drug discontinuation. These controlled studies used more rigorous methods compared to the anecdotal reports of persistence.

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####  Guideline Statement 16 

**Clinicians may consider 5-ARIs as a treatment option to reduce intraoperative bleeding and peri- or postoperative need for blood transfusion after transurethral resection of the prostate (TURP) or other surgical intervention for BPH. (_Expert Opinion_)**

Discussion

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#### Discussion

Four randomized, placebo-controlled, well-executed studies,146-149 two non-controlled studies,150, 151 and one randomized study with poorly defined methods of measuring blood loss152 explored the ability of 5-ARIs prior to surgery to reduce blood loss associated with TURP. One of the randomized and the two non-randomized studies showed a reduction in blood loss or transfusion requirements. Other studies found no significant differences between the treatment group and placebo for blood loss during surgery, excessive or severe bleeding, or clot retention.147 While surgical side effects may be mitigated by a short timeframe of use before surgery, the prescriber and patient should consider medication side effects prior to deciding to move forward with pre-surgical 5-ARI treatment.

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####  Phosphodiesterase-5 Inhibitor (PDE5) 

#### Guideline Statement 17

**For patients with LUTS/BPH irrespective of comorbid erectile dysfunction (ED), 5mg daily tadalafil should be discussed as a treatment option. (_Moderate Recommendation; Evidence Level: Grade B_)**

Discussion

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#### Discussion

In 2002 Sairam first suggested that PDE5s could improve urinary symptom scores in men attending the andrology outpatient clinic for ED.153 In 2006, Mulhall confirmed this pilot evidence in a population of men with comorbid ED and mild to moderate LUTS.154 These studies were small, non-controlled cohorts. The following year, in an RCT of men with LUTS/BPH (with or without ED), McVary established the emerging role of PDE5s as an effective and well-tolerated treatment for LUTS.155

The majority of studies address the impact of PDE5s on LUTS/BPH used tadalafil. As such, the Panel is compelled to stress the well-documented impact of this agent on LUTS/BPH compared to other PDE5s in the overall summary. The mechanism of action of this PDE5 effect is only partially understood. Additionally, given the commonly co-morbid conditions of LUTS/BPH and ED, patients should be made aware that tadalafil improves EF in men with LUTS/BPH with and without co-morbid ED with LUTS/BPH.

The evidence review identified 10 key reports from 10 trials that compared tadalafil 5 mg to placebo (n=5,129).155-164 One study started with 5 mg and escalated the dose to 20 mg after 6-weeks.155 All studies had a relatively short follow-up period of 12 weeks and were industry funded. Seven trials were conducted in multiple countries, one in Japan, one in Korea, and one in the US. Eight trials were rated as low ROB156-162 and 2 as moderate.155, 164 All trials included men with an IPSS of 13 or more. The mean age was 63 years (61-66), and baseline IPSS was 16 points (16-22), indicating moderate symptom severity. Seven trials reported a mean BPH Impact Index score of 5.3 at baseline.111, 155-159, 164 Four trials reported that 80% of participants had ED at baseline (range 59%-71%).111, 157, 159, 164 ED was reported in 66% of participants in one trial155 and 100% of participants in another.164

In one trial with a moderate ROB and 281 participants who were randomized to tadalafil or placebo after a 4-week placebo run-in period, participants randomized to tadalafil started at a dose of 5 mg daily and were escalated to a dose of 20 mg daily after 6 weeks.155 At 3 months, participants in the tadalafil group on the 20 mg dose had a greater response to treatment, defined as a change from baseline of ≥3 points in IPSS, compared to placebo, 61% versus 43% ([RR: 1.43; 95%CI: 1.13, 1.80]; [ARD: 18%; 95%CI: 7, 30]; Number Needed to Treat [NNT]=6). On the 5 mg dose at 6 weeks, the proportion of participants on the 5 mg dose of tadalafil was also significantly greater than participants on placebo 49% versus 36%.

Conversely, tadalafil resulted in little to no difference compared to placebo in the IPSS change from baseline compared to placebo across the 10 trials, -5.4 points versus -3.6 points ([MD: -1.7 points; 95%CI: -2.14, -1.35]; high quality of evidence) (**Figure 3**), and IPSS-QoL ([MD: -0.3 points; 95%CI: -0.35, -0.17]; high quality of evidence) compared to placebo.155-159, 161, 162, 164 The minimal detectable difference of 3 points was not achieved for either measure. The tadalafil group had a greater mean change in the BPH Impact Index versus placebo, exceeding the minimal detectable difference of 0.4 points (MD: -0.6 points; 95%CI: -0.81, -0.37).155-160, 163 Four trials reported little to no difference between groups in frequency of nocturia (MD: -0.13 times per night; 95%CI: -0.26, 0.01).155-159 It should be noted that nocturia is the one component of the IPSS least likely to improve with any medical treatment.

Figure 3 displays the mean change from baseline in IPSS from the 10 RCT consisting of 3,754 participants. As noted, the mean change in the tadalafil arms was -5.4 points while the controls noted a mean change -3.6 points for a mean difference of **1.74 lower.** This demonstrates that tadalafil results in little to no difference in mean change in IPSS compared to placebo. However, in data not shown, percentage of treatment responders, defined as ≥3 points in the IPSS scale decrease in 281 participants (1 RCT) showed a relative effect of **RR 1.43**(1.13 to 1.80) suggesting that tadalafil probably greatly increases response to the IPSS compared to placebo.

Overall withdrawals were reported in 8% of participants in the tadalafil group and in 9% in the placebo group ([RR: 0.94; 95%CI: 0.77, 1.16]; [ARD: -0.5%; 95%CI: -2.2, 1.3]). Compared with placebo, tadalafil resulted in little to no difference in withdrawals due to adverse events, 3% versus 2% ([RR: 1.64; 95%CI: 1.02, 2.62]; [1%; 95%CI: 0.3, 2.1]; moderate quality of evidence).156-164 Tadalafil increased adverse events compared to placebo (26% versus 22%; [RR 1.22; 95%CI: 1.09, 1.37]; [ARD: 5%; 95%CI: 2, 8]; Number Needed to Harm [NNH]=20; high quality of evidence). Headache, nasopharyngitis, and back pain were the most commonly reported adverse events and incidences were comparable between treatment groups.

**Figure 3: Mean Change from Baseline in IPSS in 10 RCTs**

[![](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Fig%203-%20b.png)](images/Guidelines/Guideline%20Images/BPH/2023/BPH-%20Fig%203-%20b.png)****

Tadalafil=1,877; Placebo=1,877  
I2=0%

**Low-Dose Daily Tadalafil Versus Tamsulosin**

The studies reviewed by the Panel noted that the impact of low-dose daily tadalafil on LUTS appears similar to that seen with tamsulosin. Although adverse events and treatment withdrawal profiles between the agents may differ qualitatively, there is little to no difference between these two classes.

In a single trial comparing tadalafil 5 mg daily to tamsulosin 0.4 mg daily, the proportion of participants with a 3-point improvement in IPSS was not reported.158 At 3 months, this trial found little to no difference between groups in mean change in IPSS (-6.3 versus -5.7 points; [MD: -0.60 points; 95%CI: -1.99, 0.79]; high quality of evidence) and IPSS-QoL ([MD: -0.20 points; 95%CI: -0.48, 0.08]; high quality of evidence).158 Mean change in BPH Impact Index (BII) or frequency of nocturia did not differ between groups (decrease of 0.5 times per night for both groups; [MD: 0 times per night; 95%CI: -0.28, 0.28]). There was more improvement in the International Index of Erectile Function (IIEF) with tadalafil compared to tamsulosin, 6 points versus 2 points ([MD: 4.3 points; 95%CI: 2.09, 6.51]; moderate quality of evidence).158

**Tadalafil impact on Urodynamic Measures**

While the impact of tadafil on LUTS/BPH symptoms has been described, the use of this drug does not appear to improve urodynamic profiles.165 During a multicenter, randomized, double-blind, placebo controlled clinical trial comparing once daily tadalafil 20 mg versus placebo over 12 weeks in men with LUTS/BPH, investigators assessed change in detrusor pressure at maximum urinary flow rate. Urodynamic measures remained unchanged during the study with no statistically significant difference between tadalafil and placebo in change in any urodynamic parameter assessed including Qmax, maximum detrusor pressure, BOO index or bladder capacity (all measures p ≥0.13). While no improvement was seen, it is important to note that tadalafil also showed no negative impact on bladder function. The lack of improvement of urodynamic profile is clearly paradoxical and serves as a potential warning to clinicians that tadalafil has no established role in men with impaired bladder function, urinary retention, or those in the midst of a TWOC.

**Treatment of LUTS/BPH with Sildenafil**

Although tadalafil is the only PDE5 approved by the FDA for treatment of LUTS, there are limited data suggesting sildenafil may also be useful. One high-quality randomized trial conducted in the US with 369 subjects showed that at 12 weeks, sildenafil 50-100 mg improved the IPSS by 6.3 points compared to 1.9 for placebo.166 IPSS change was also greater in the sildenafil group with severe and moderate LUTS. Furthermore, sildenafil resulted in significant improvement in IIEF-EF compared to placebo, 10 versus 3 points. Common adverse events with use of sildenafil included headache (11% versus 3% placebo) and flushing. The withdrawal rate due to adverse events was slightly higher (5% sildenafil to 3% placebo). Thus, sildenafil could be considered when tadalafil is not available and alpha blockers are not tolerated. Similar to statements in the AUA ED Clinical Guideline, sildenafil improves EF in men with LUTS/BPH with and without co-morbid ED.167

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####  Combination Therapy 

#### Guideline Statement 18

**5-ARI in combination with an alpha blocker should be offered as a treatment option only to patients with LUTS associated with demonstrable prostatic enlargement as judged by a prostate volume of > 30g on imaging, a PSA >1.5ng/mL, or palpable prostate enlargement on** **DRE. (_Strong Recommendation; Evidence Level: Grade A_)**

Discussion

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#### Discussion

In the 1990s, two studies of 12 months duration were conducted testing the hypothesis that combination medical therapy may be superior to monotherapy.168, 169 The VA CO-OP used placebo versus terazosin 10mg versus finasteride 5mg versus combination, and the European PREDICT trial used doxazosin instead of terazosin. Both studies concluded that combination therapy was **_not_ **superior to alpha blocker monotherapy. They were criticized on account of the relatively short duration of only one year and the fact that patients were enrolled regardless of prostate size and serum PSA leading to a study population of, at, or below average sized prostates and serum PSA values. A meta-analysis has shown that finasteride was superior to placebo only in men with enlarged prostates and/or higher serum PSA values.94, 96

The National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK) also conducted a combination therapy study in the 1990s in which the primary outcome parameter was a composite progression endpoint:19, 122 MTOPS study enrolled over 3,000 men with at or below average sized prostates (similar to the VA COOP) and randomized them to placebo versus doxazosin 4 mg or 8 mg daily versus finasteride 5 mg daily versus combination of doxazosin and finasteride.

Men were treated and followed for up to 5.5 years. The risk of overall clinical progression, defined as an increase above base line of at least four points in the AUA-SI, AUR, urinary incontinence, renal insufficiency, or recurrent UTI, was significantly reduced by doxazosin (39% risk reduction; p<0.001) and finasteride (34% risk reduction; p=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66% for the comparison with placebo; p<0.001) was significantly greater than that associated with doxazosin (p<0.001) or finasteride (p<0.001) alone. The risks of AUR and the need for invasive therapy were significantly reduced by combination therapy (p<0.001) and finasteride (p<0.001) but not by doxazosin. Doxazosin (p<0.001), finasteride (p=0.001), and combination therapy (p<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (p=0.006) and finasteride (p<0.001) alone. Although not a primary outcome, symptom and flow rate improvement were superior in the combination therapy arm compared to both monotherapies.

The second major combination therapy study conducted was the CombAT trial in which 4,844 men were randomized to receive tamsulosin 0.4 mg versus dutasteride 0.5 mg versus combination therapy with both over four years (no placebo control group was used).111 In contrast to prior studies, but in keeping with the study protocol of only enrolling patients with prostatic enlargement in LUTS/BPH trials with dutasteride, men had to have a prostate volume > 30 mL by TRUS and a serum PSA of >1.5 ng/mL. Combination therapy resulted in significantly greater improvements in symptoms versus dutasteride from month 3 and tamsulosin from month 9, and in BPH-related health status from months 3 and 12, respectively. A significantly greater improvement from baseline in Qmax for combination therapy versus dutasteride and tamsulosin monotherapies from month 6 was also noted. There was a significant increase in drug related adverse events with combination therapy versus monotherapies.

Four-year data from the CombAT trial was published in 2014.27 Interestingly, dutasteride and combination therapy demonstrated similar improvements for men with a baseline prostate volume ≥60mL and PSA≥4ng/mL; however, combination therapy was superior if prostate volume and PSA were lower than these thresholds (but still above study inclusion criteria of prostate volume>30mL and PSA>1.5ng/mL). Qmax improvement was seen in combination therapy compared to placebo, but not dutasteride monotherapy. Qmax improvements were more profound with increasing prostate volume and PSA levels in combination therapy subjects.

In a study focused only on Asian men and using a 0.2 mg tamsulosin dose, men with characteristics often associated with disease progression obtained better symptomatic benefit from combination therapy compared to monotherapy with tamsulosin. In the 24-month study, improvements in Qmax and prostate volume reduction were more prominent in the combination therapy group. Reductions in the risk of AUR and BPH related surgery were also seen.

In a study looking at initiation of combination dutasteride and tamsulosin, or no medication, Roehrborn et al.121 found that initial combination medication intervention improved QoL outcomes compared to later initiation of tamsulosin when men had disease progression.

Providers may start combination therapy with the intention of later discontinuing the alpha blocker (sometimes called "Withdrawal Therapy"). The rationale for this treatment is for men to initially gain the benefit of the alpha blocker and once the efficacy of the 5-ARI is fully developed at a later time, the alpha blocker may be removed. While this is a reasonable strategy, the concept has not been studied rigorously, and there are insufficient data to gauge the utility of this approach or the duration at which combination therapy should be continued before cessation of the alpha blocker.

As stated previously, providers do not need to obtain a PSA solely for determination of 5-ARI efficacy as part combination therapy, although knowledge of a pre-existing value may help guide treatment options.

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####  Guideline Statement 19 

**Anticholinergic agents, alone or in combination with an alpha blocker, may be offered as a treatment option to patients with moderate to severe predominant storage LUTS. (_Conditional Recommendation; Evidence Level: Grade C_)**

Discussion

×

#### Discussion

Anticholinergics have been approved and used for OAB symptoms in men and women as detailed in the AUA/SUFU non-neurogenic OAB Guideline.170 Although the exact cause may be varied, both storage LUTS and OAB have the same symptoms. While anticholinergics alone have been used for OAB symptoms in men and women, there has been some reluctance on the part of clinicians to use them alone in patients with LUTS/BPH due to the potential risk of worsening bladder residuals or retention. However, studies show the risk of urinary retention to be low in appropriately selected patients.

**Anticholinergics as monotherapy**

One large (n=222) low ROB, 12-week trial comparing solifenacin 6 and 9 mg to placebo in men with moderate-severe LUTS (IPSS≥13) showed no significant difference in IPSS (-6.3 placebo, -6.0 solifenacin 6 mg, -6.3 solifenacin 9 mg).171 Acute urinary retention requiring catheterization occurred only in 1 of 43 subjects on solifenacin 9 mg and none in the other groups.171 Withdrawals due to adverse events were very low in all groups.

Another large (n=425) US-based, 12-week trial compared tolterodine 4 mg to placebo in men with moderate to severe LUTS (IPSS≥12), resulting in IPSS changes of -6.7 for tolterodine compared to -6.2 for placebo. Post hoc analysis showed that in men with prostates <29 mL, IPSS change was -7.8 for tolterodine compared to -6.1 for placebo (p=0.06).172-175 There was no difference in the number of withdrawals due to adverse events or episodes of urinary retention between the groups.

A safety trial was conducted in patients with urodynamically-proven obstruction and detrusor over activity, comparing tolterodine 2 mg to placebo. The results showed mild increase in PVR (25 mL versus 0 mL) and mild decrease in bladder contractility index, with urinary retention occurring in only one patient, who was in the placebo group. The findings were felt to be clinically insignificant, and the authors concluded that tolterodine is safe to use in men with BOO.176

While anticholinergics have been used safely in men with storage LUTS, a PVR should be obtained and the usual precautions for the use of anticholinergic medications (e.g., gastric emptying/ GI motility issues, narrow angle glaucoma) should be followed. Furthermore, there have been recent publications suggesting an association between use of anticholinergic drugs and increased risk of dementia in patients over 55.177, 178 The side effects, especially in patients over 70, can be significant and the benefits and risks of treatment should be carefully weighed and discussed with the patient and family.179

**Anticholinergic therapy in combination with alpha blockers**

As for combination therapy of alpha blockers and anticholinergics, there have been numerous trials comparing combinations to placebo, or to alpha blocker alone. One low ROB trial (n=271) conducted in the Netherlands compared solifenacin 3 mg and tamsulosin 0.4 mg to placebo and showed clinically significant improvement in IPSS in the combined group compared to placebo at 12 weeks. Acute urinary retention occurred in 1% of the combined group; constipation and dry mouth were also more common in this group.171

Three other trials (n=1,674) compared solifenacin 6 or 9 mg (nonstandard dosing compared to typical 5mg and 10mg) and tamsulosin 0.4 mg to placebo. All were low ROB randomized controlled 12-week trials. Mean IPSS improvement in the combined tamsulosin/solifenacin arms were -7.34 and -6.58 compared to -5.73 for placebo. Overall IPSS improvement was not significant based on a high level of certainty, while adverse events in the combined group were higher (moderate certainty); there was no change in acute retention or withdrawals between the groups.171, 172, 180

One double-blind RCT lasting 12 weeks showed tolterodine 4 mg and tamsulosin 0.4 mg compared to placebo had statistically significant improvement in frequency, urgency, urge incontinence, and nocturia along with patient-reported benefit. IPSS change was -8.02 versus -6.19 for placebo (p=0.003).181

A total of ten trials compared tamsulosin/solifenacin to tamsulosin alone. Doses of solifenacin ranged from 5 to 9 mg and tamsulosin from 0.2 to 0.4 mg.171, 180, 182 The mean difference in IPSS favored the combined group but only by 0.39-0.43 (-7.00 compared to -6.63). Thus, the difference in IPSS was not significant based on a high level of certainty, and while the adverse events increased slightly, the retention rate was similar (moderate certainty).

Trials comparing tolterodine 4 mg and alpha blocker to alpha blocker alone show significant improvement in the combined group in percentage of responders with > 3-point IPSS decrease. However, mean IPSS change showed little to no difference (-5.9 versus -5.6). Withdrawals due to adverse events in the combined group were slightly higher (low certainty).183-185

One large trial compared add on fesoterodine 4 or 8 mg and alpha blocker to placebo and alpha blocker over 12 weeks. This was a moderate ROB international trial in patients with moderate LUTS (baseline IPSS 19) and PVR<200 mL. IPSS change was -4.4 for both add on fesoterodine and placebo (moderate certainty), while adverse events related withdrawals were higher in the fesoterodine group (moderate certainty).186

An older 12-week double-blind RCT compared oxybutynin 10 mg and tamsulosin 0.4 mg to tamsulosin and placebo. Baseline IPSS was 20 and response to treatment defined as ≥3 point reduction in IPSS was greater (75%) in the combined drug group compared to placebo (65%). Mean IPSS change was -6.9 versus -5.2, and there was no difference in adverse events or withdrawals due to adverse events (moderate certainty).

Overall, it makes intuitive sense to use anticholinergics combined with alpha blockers in selected patients with storage predominant LUTS/BPH. However, the IPSS improvement in men with combined alpha blocker and anticholinergic compared to alpha blocker alone is variable. Since there are increased adverse events, one can consider initially starting with alpha blocker alone and adding anticholinergics in selected cases. However, further studies with larger sample sizes are needed to determine whether combination therapy enhances the symptom response, or if the response is driven by the alpha blocker alone.

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####  Guideline Statement 20 

**Beta-3-agonists in combination with an alpha blocker may be offered as a treatment option to patients with moderate to severe predominate storage LUTS. (_Conditional Recommendation; Evidence Level: Grade C_)**

Discussion

×

#### Discussion

**Mirabegron Versus Placebo**

Unlike the anticholinergic agents described in Statement 19, monotherapy with a beta-3-agonist has, thus far, not been shown to lead to significant differences in LUTS secondary to BPH. Nitti et al.187 compared mirabegron 50 mg and 100 mg to placebo (n=200) with a follow-up of 12 weeks. The mean age was 63 years, and the baseline BMI was 29 kg/m2. The trial included men with a baseline IPSS of more than 8 with a mean of 20 points, indicating severe LUTS.

At short-term follow-up of 12 weeks, mirabegron 50 and 100 mg resulted in little to no difference in IPSS or adverse events.187 Mirabegron was safe at both dosages with no increased risk of hypertension as compared to placebo. IPSS scores were reduced in the mirabegron 50 mg, 100 mg, and placebo groups by 6.2, 4.8, and five points, respectively. Compared to placebo, mirabegron 50 mg or mirabegron 100 mg resulted in little to no difference in mean change in IPSS (low quality of evidence). Treatment response in IPSS, IPSS-QoL, and nocturia were not reported.

No adverse events related to sexual function were reported. Incidence of urinary retention did not differ between mirabegron 100 mg and placebo (2%).187 Overall withdrawal from participation was 7% in the mirabegron group and 3% in the placebo group (RR: 2.41; 95%CI: 0.54, 10.67). Study attrition due to adverse events did not differ between the groups, 3% versus 3% (RR: 0.96; 95%CI: 0.18, 5.12; low quality of evidence). Incidence of hypertension was 4% with mirabegron 50 mg, 3% with mirabegron 100 mg, and 3% with placebo.

**Combined Mirabegron/Silodosin Versus Active Comparator**

Matsukawa et al.188 compared a combination of mirabegron 50 mg and silodosin 8 mg to a combination of fesoterodine 4 mg and silodosin 8 mg (n=120). This open-label study was conducted in Japanese men with persistent OAB symptoms and had a follow-up of 12 weeks. The trial included men with a baseline IPSS of more than 8. Mean age was 72 years and IPSS was 17 points, indicating moderate LUTS. Comorbidities at baseline included diabetes (24%), hypertension (57%), and hyperlipidemia (47%).188

At 12 weeks, combined mirabegron and silodosin resulted in little to no difference in IPSS (MD: 0.30; 95%CI: -1.27, 1.87; moderate quality of evidence) and IPSS-QoL (MD: 0.40; 95%CI: -0.40, 0.81; moderate quality of evidence) compared to combined fesoterodine and silodosin. Treatment response in IPSS and nocturia were not reported.188 Side effects of dry mouth and constipation favored mirabegron over fesoterodine. Other side effects appear to be similar.

No adverse events related to sexual function or cases of urinary retention were reported in any group. Overall withdrawals were 13% with combined mirabegron and silodosin and 17% with combined fesoterodine and silodosin (RR: 0.80; 95%CI: 0.34, 1.89). Dry mouth and constipation occurred in 3% and 2% of participants in the mirabegron combination group compared to 12% and 5% in the fesoterodine combination group. Dizziness was also reported in 3% of participants in the combined mirabegron group compared to 2% in the combined fesoterodine group.

**Combined Mirabegron and doxazosin versus active comparator**

Elbaz et al studied a combination of mirabegron 50 mg and doxazosin 2 mg with a combination of tolterodine 4 mg and doxazosin 4 mg in 55 Egyptian men with LUTS/Obstructive symptoms and ED.189 This single-blinded (patients) study was conducted over 12 weeks. The trial excluded men with a high PVR volume (> 150 mL). Mean age in the study was 59.5 years and IPSS was 17 points, indicating moderate LUTS. Comorbidities at baseline included diabetes (21%) and hypertension (23%).

At 12 weeks, combined mirabegron and doxazosin did not show great difference in IPSS (MD -2.0 points [95% CI -4.94 to 0.94]) and IPSS-QoL (median scores at follow-up were both 1; moderate certainty of evidence) compared with combined tolterodine and doxazosin. Treatment response in IPSS and nocturia were not reported.189 However, by week 12, International Index of Erectile Function-15 total function scores improved by at least five points from baseline in 92% in the combined mirabegron and doxazosin group compared with 26% in the tolterodine and doxazosin group (p<.001). Withdrawals due to adverse events were not reported and no cases of urinary retention were reported in any group. Rates of overall withdrawals were similar, 14% and 15% for the combined mirabegron and combined tolterodine groups, respectively (RR 0.96 [95% CI 0.27 to 3.47]). Dry mouth occurred in 4% of participants in the mirabegron combination group compared with 13% in the tolterodine combination group. Constipation and headaches were also reported in a few patients.

Combination therapy with a beta-3-agonist appears to be reasonably safe and tolerated and can lead to improvement in symptoms similar to those seen with anticholinergics. Therefore, in older patients or others where anticholinergic therapy is not recommended, a beta-3-agonist can be utilized. However, further studies with larger sample sizes are needed to determine whether combination therapy enhances the symptom response, or if the response is driven by the alpha blocker alone.

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####  Guideline Statement 21 

**Clinicians may offer the combination of low-dose daily 5mg tadalafil with alpha blockers for the treatment of LUTS/BPH. (_Conditional Recommendation; Evidence Level: Grade C_)**

Discussion

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#### Discussion

**Combination of Low-Dose Daily Tadalafil with Alpha Blockers**

Clinicians are often asked if there is merit to the use of combination of low-dose daily tadalafil with alpha blockers. Data on this is evolving with no clear definition conclusions due to lack of diverse cohorts and of long term follow up.

In the review of the available data and as part of a systematic review, the Panel identified one trial that compared a combination of tadalafil 5 mg and various alpha blockers to a combination of a placebo and an alpha blocker. In the Goldfischer trial (n=318)190 the participants were receiving treatment with an alpha blocker therapy prior to randomization. Tamsulosin was the most commonly used alpha blocker (53%). This low ROB trial had a follow-up of 12 weeks, was conducted in the US, and was industry funded. Mean age was 67 years, and baseline IPSS was 14 points, indicating moderate symptom severity.

Similarly, the search found another trial that enrolled men with LUTS and ED that compared a combination of tadalafil 5 mg and tamsulosin 0.4 mg to tadalafil 5 mg (n=340).191 This low ROB trial had a follow-up of 12 weeks. Mean age was 63 years and baseline IPSS was 21 points, indicating severe LUTS. Mean IIEF-EF score was 14.4, indicative of mild-moderate ED.

A third trial compared a combination of tadalafil 5 mg and silodosin 8 mg with silodosin 8 mg alone (n=256 randomized, 207 analyzed).192 Treatments were administered daily with follow-up after three months of treatment. Mean age of study participants was 63 years in both the combination and single medication groups. Baseline IPSS was 21.3 and 20.8, respectively. Baseline comorbidities were not reported.

In the first trial, combined tadalafil and alpha blocker resulted in little to no difference in IPSS compared to alpha blocker alone at 12 weeks (-2.3 versus -1.5 points; MD: -0.79 points; 95%CI: -2.00, 0.42; moderate quality of evidence).190 In the second trial, a combination of tadalafil 5 mg and tamsulosin 0.4 mg compared to tadalafil alone resulted in little to no difference in IPSS (-9.5 points versus -8.1 points; MD: -1.3 points; 95%CI: -2.54, -0.10; high quality of evidence) and IPSS-QoL (MD: -0.1 points; 95%CI: -0.39, 0.11; high quality of evidence).191 There was little to no difference in change in IIEF (9.2 points versus 9.5 points; MD: -0.3 points; 95%CI: -1.47, 0.83; moderate quality of evidence). In the third trial, there is likely little to no difference in mean change in IPSS scores between the combination and silodosin alone groups (-5.6 versus -4.1 points; MD 1.5 points [95% CI 0.82 to 2.18]; moderate certainty of evidence).192

In the first trial, outcomes related to sexual function were not reported.190 Overall withdrawals were 11.4% in the combined tadalafil 5 mg and alpha blocker group and 12.5% in the alpha blocker group ([RR: 0.9; 95%CI: 0.50, 1.66]; [ARD: -1.1%; 95%CI: -8.2, 6]). Combined tadalafil and alpha blocker resulted in an increase in reported adverse events compared to alpha blocker alone ([RR: 1.26; 95%CI: 0.95, 1.68]; [ARD: 9%; 95%CI: -2, 19]; low quality of evidence). In the second trial, overall withdrawals were 18.3% with combination therapy and 10.5% with tadalafil monotherapy ([RR: 1.7; 95%CI: 1.01, 2.99]; [ARD: 7.8%; 95%CI: 0.4, 15]). Combined therapy increased adverse events compared to tadalafil alone ([RR: 1.4: 95%CI: 0.89, 2.33]; [ARD: 6% 95%CI: -2, 14]; low quality of evidence). In the third trial, there is also little to no difference in mean change in IIEF scores (MD -0.40 points [95% CI -1.00 to 0.20]; moderate certainty of evidence).192

**Other PDE5, Alpha Blocker Combinations:**

A small trial compared sildenafil 50 mg with a nonstandard dose of doxazosin 2 mg (n=100).193 The trial had a follow-up period of 4 months. At 4 months, the sildenafil group had less improvement in IPSS compared with doxazosin, -2.3 points versus -3.4 points. Improvement in IIEF-EF was 4.6 points in the sildenafil group and 2.0 points in the doxazosin group. Responders to treatment based on IPSS, IPSS-QoL change, nocturia, and adverse events were not reported.193

While not as extensively studied as tadalafil, sildenafil has been combined with alpha blockers. In one study evaluating both IPSS and IIEF scores, sildenafil 25 mg with tamsulosin 0.4 mg resulted in significant changes in the IPSS.194 At six months, the IPSS mean change was -7.7 in the combined group compared to -4.3 in the tamsulosin only group. The IIEF improved by 9 points in the combined group compared to 2 points in the tamsulosin group, a highly significant difference. Thus, addition of sildenafil 25 mg daily may be considered in patients with LUTS/BPH who have an inadequate response to tamsulosin, especially if they desire concomitant therapy for ED.

One trial (n=60)195 compared vardenafil 10 mg plus tamsulosin 0.4 mg to tamsulosin 0.4 mg alone. At baseline, IPSS was 20 with only a 2-point change at 12 weeks (was -5.8 in the combined group and -3.7 in the tamsulosin only group (MD -2.1). This study suggests that the addition of vardenafil is minimal and may offer no advantages in symptom improvement over tamsulosin alone. There were more adverse events in the combined group but no change in overall withdrawals.

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####  Guideline Statement 22 

******Clinicians may offer the combination of low dose daily tadalafil 5mg with finasteride for the treatment of LUTS/BPH. (_Conditional Recommendation; Evidence Level: Grade C_)**

Discussion

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#### Discussion

Clinicians are occasionally asked about the use of low-dose daily tadalafil with finasteride. Similar to combination therapy of alpha blockers and PDE-5 for LUTS/BUH, there a lack of long term follow up.

The search identified one trial that compared a combination of tadalafil 5 mg and finasteride 5 mg to a combination of finasteride and placebo (n=696).196 This low ROB trial had a follow-up of six months. The trial was conducted in North America, South America, and Europe. Mean age was 64 years and baseline mean IPSS was 17 points. ED was reported in 65% of participants.

At six months, the combination tadalafil and finasteride group had little to no difference in response to treatment, defined as a change from baseline of ≥3 points in IPSS, compared to finasteride, 71% versus 70% ([RR: 1.02; 95%CI: 0.92, 1.12; [ARD:1%; 95%CI: -6, 8; moderate quality of evidence).197 Overall, a combination of tadalafil and finasteride resulted in little to no difference in mean change in IPSS, -5.5 versus -4.5 points (MD: 1.0 points; 95%CI: 1.83, 0.17; high quality of evidence) and IPSS-QoL (MD: 0.2 points; 95%CI: 0.48, 0.08; high quality of evidence) compared to finasteride. The minimal detectable difference was not achieved for either measure. There was also no difference between groups in frequency of nocturia based on IPSS (MD: 0 times per night; 95%CI: -0.28, 0.28). However, combination tadalafil and finasteride resulted in improvement in IIEF-EF scores compared to finasteride alone in sexually active men (RR: 4.7; 95%CI: 3.04, 6.38).

Compared to finasteride alone, overall withdrawals were less in the combined tadalafil and finasteride group, 11.6% versus 18.3% (RR: 0.63; 95%CI: 0.44, 0.91) but there was little to no difference between groups in withdrawals due to adverse events, 1.2% versus 2.9% (RR: 0.41; 95%CI: 0.13, 1.28; low quality of evidence). Combined tadalafil and finasteride resulted in an increase in adverse events compared to finasteride alone (31% versus 27%; RR: 0.41; 95%CI: 0.13, 1.28; low quality of evidence). The Panel consensus was that the impact of the combination of low-dose daily tadalafil with finasteride offers little or no advantages in symptom improvement over finasteride alone in the short term.

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####  AUR Outcomes 

#### Guideline Statement 23

**Physicians should prescribe an oral alpha blocker prior to a voiding trial to treat patients with AUR related to BPH. (_Moderate Recommendation; Evidence Level: Grade B_)**

####  Guideline Statement 24 

**Patients newly treated for AUR with alpha blockers should complete at least three days of medical therapy prior to attempting trial without a catheter (TWOC). (_Expert Opinion_)**

####  Guideline Statement 25 

**Clinicians should inform patients who pass a successful TWOC for AUR from BPH that they remain at increased risk for recurrent urinary retention. (_Moderate Recommendation; Evidence Level: Grade C_) **

Discussion

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#### Discussion

Fourteen randomized clinical trials have investigated pharmacologic treatment of AUR in men.198-211 The studies differ by definition of AUR (500- 1,500 mL), inclusion criteria, treatment length, and follow-up (1 day to 24 months). At baseline, mean age across the studies was 68 years (range 59-75 years). Mean IPSS was 16 at baseline (range 10-26) and reported in six trials.198-202, 211 The above guidelines were determined by assessment of successful TWOC at 1 month after the intervention (unless otherwise specified), urinary retention at 12 months, IPSS at 12 months, and QoL at 12 months.

Men prescribed alfuzosin (5mg twice daily and 10mg daily) or tamsulosin (0.4mg daily) demonstrated improvement in AUR signs and symptoms, as measured by TWOC. In the alfuzosin studies, follow-up ranged from 2 days to 2 years or time to surgery. Pooled results showed successful TWOC may be greatly increased with alfuzosin compared to placebo, 60% versus 39% (OR: 2.28; 95%CI: 1.55, 3.36). The tamsulosin studies had similar follow-up limitations (5 days to 6 months) but similarly showed efficacy. Pooled results for this medication showed that successful TWOC compared to placebo was 47% versus 29% (OR: 2.40; 95%CI: 1.29, 4.45). Doxazosin and silodosin have also been studied but have less data to support a recommendation either as monotherapy or combined with another alpha blocker.

Given the lack of standardized follow-up, it is challenging to determine long-term efficacy of alpha blocker therapy in treating AUR. All trials report a significant number of patients with subsequent urinary retention and LUTS after treatment occurring days to months later, who then require catheterization or surgical outlet procedures.

In addition to alpha blockers, 5-ARIs have been shown to prevent progression of AUR attributed to LUTS/BPH. MTOPS showed the risks of AUR and need for invasive therapy were significantly reduced by combination therapy of doxazosin and finasteride (p<0.001) and finasteride monotherapy, (p<0.001), but not by doxazosin, alone. As regards dutasteride, when assessing for absolute risk reduction for AUR as compared to placebo, there were noticeable differences both with AUR (6% risk reduction) and BPH-related surgery (3.8%) in the dutasteride group.112 Further information regarding 5-ARIs and results can be found in statements 13, 15, and 18.

Practitioners should also consider delaying a voiding trial in patients with an active UTI until the infection has resolved.

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###  Surgical Therapy 

####  Guideline Statement 26 

**Surgery is recommended for patients who have renal insufficiency secondary to BPH, refractory urinary retention secondary to BPH, recurrent urinary tract infections (UTIs), recurrent bladder stones or gross hematuria due to BPH, and/or with LUTS/BPH refractory to or unwilling to use other therapies. (_Clinical Principle_)**

Discussion

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#### Discussion

The overwhelming majority of patients with LUTS/BPH who desire treatment will choose some form of medical therapy, either with a single agent or a combination of agents with different mechanisms of action, as the first approach. Since the advent of medical therapy for BPH, this has resulted in a steady reduction in surgical therapies for this condition. In fact, between 1999 and 2005, there was a 5% per year decrease in TURP.212 When this study was updated, there was a further 19.8% decrease from 2005 to 2008.213 As a result, patients who now undergo surgery for BPH are generally older214 and have more medical comorbidities.214 In addition, "failure of medical therapy" as an indication for surgery rose from essentially 0% in 1988 to 87% in 2008.215

Despite the more prevalent use of medical therapy for men suffering from LUTS associated with BPH, there remain clinical scenarios where surgery is indicated as the initial intervention for LUTS/BPH and should be recommended, providing other medical comorbidities do not preclude this approach. Classically, these conditions include chronic renal insufficiency (defined as GFR < 60 for at least 3 months) secondary to BPH, refractory urinary retention secondary to BPH, recurrent UTIs, recurrent bladder stones or gross hematuria due to BPH, and/or with LUTS/BPH refractory to or desire to avoid other therapies.

Long standing BOO from BPH can progress to incomplete bladder emptying, bilateral hydroureteronephrosis, and, ultimately, acute and/or chronic renal insufficiency. Although transient urethral catheterization with concomitant medical therapy using an alpha-adrenergic antagonist can be considered, it is unlikely that the latter will adequately ameliorate the obstructive process to sufficiently prevent further upper urinary tract deterioration. In men with refractory urinary retention thought secondary to BPH, as opposed to that related to other etiologies (e.g., urethral stricture, neurogenic bladder), surgery should be the mainstay of therapy. Recurrent UTIs not due to other causes (e.g., bacterial prostatitis, renal calculi) and the presence of recurrent bladder calculi are generally thought to result from incomplete bladder emptying and a persistently elevated PVR. Surgical elimination of the obstruction when combined with the presence of adequate detrusor contractility should allow almost complete bladder emptying, thereby decreasing the risk of future infections.

Cystolithalopaxy can be performed concomitantly with the surgical procedure used to remove the obstructing prostate tissue and depending on the size and number of stones present, can influence the choice of surgical approach (e.g., transurethral, open, or laparoscopic). It has been shown that the use of a 5-ARI (i.e., finasteride, dutasteride) can be an effective treatment for gross hematuria secondary to BPH (see statement 42 for further discussion).216 If, however, gross hematuria persists, surgical removal/ablation of the offending adenomatous tissue should be the next step unless precluded for other reasons. Finally, in patients with medically refractory LUTS associated with BPH or who choose not to pursue other minimally invasive therapies, surgery should be offered.

It is important to note that an elevated PVR should not be used as the only indication for bladder outlet surgery. The AUA Non-Neurogenic Chronic Urinary Retention White paper suggests that patients presenting with non-neurogenic chronic urinary retention should be evaluated for safety issues mentioned above (renal insufficiency, chronic UTI) and then for symptoms which impact urinary QoL (obstructive urinary symptoms, urinary frequency). Safety and QoL issues can be treated with bladder drainage such as intermittent catheterization while the patient is being evaluated for BOO. A patient with an incidentally discovered elevated PVR who does not have any safety issues related to retention or does not report any bothersome urinary symptoms can be followed with longitudinal safety and QoL assessments.217

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####  Guideline Statement 27 

**Clinicians should not perform surgery solely for the presence of an asymptomatic bladder diverticulum; however, evaluation for the presence of bladder outlet obstruction (BOO) should be considered. (_Clinical Principle_)**

Discussion

×

#### Discussion

Indications for surgical intervention include recurrent UTI, recurrent bladder stones, progressive bladder dysfunction (i.e., loss of low-pressure bladder storage function due to poor compliance), and renal insufficiency secondary to progressive bladder dysfunction. Prior to surgery for bladder diverticulum, clinicians should perform assessment for BOO and treat as clinically indicated.

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####  Transurethral Resection of the Prostate (TURP) 

#### Guideline Statement 28

******TURP should be offered as a treatment option for patients with LUTS/BPH. (_Moderate Recommendation; Evidence Level: Grade B_)**

Discussion

×

#### Discussion

TURP remains the historical standard by which all other subsequent surgical approaches to treatment of BPH are compared and serves as the reference group for all other techniques in this Guideline. TURP helps to reduce urinary symptoms associated with BPH, including frequent/urgent need to urinate, difficulty initiating urination, prolonged urination, nocturia, non-continuous urination, a feeling of incomplete bladder emptying, and UTIs. Successful TURP can relieve symptoms quickly with most men experiencing significantly stronger urine flow within days of the procedure. TURP remains the most frequently taught and utilized procedure for the treatment of symptomatic BPH and the one with which nearly all urologists have experience and ability to perform.

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####  Guideline Statement 29 

******Clinicians may use a monopolar or bipolar approach to TURP as a treatment option, depending on their expertise with these techniques. (_Expert Opinion_)**

Discussion

×

#### Discussion

A large body of literature has been published in recent years regarding certain modifications of the standard TURP using monopolar energy, most notably the use of bipolar energy transmission.

Contrary to monopolar TURP, bipolar energy does not travel through the body to reach a skin pad as the energy is confined between an active (resection loop) and a passive pole situated on the resectoscope tip. While monopolar TURP requires the use of either iso-osmolar solutions of sorbitol, mannitol, or glycine, bipolar TURP is performed in 0.9% NaCl solution. This reduces (if not eliminates) the risk for acute dilutional hyponatremia during prolonged resection, which may lead to the so-called TUR syndrome.

Regarding the comparative efficacy, effectiveness, and safety of monopolar versus bipolar TURP, there are five systematic reviews and meta-analyses published between 2009 and 2015 that compared bipolar TURP to monopolar TURP.218-222 None of the authors found significant differences in terms of improvement in IPSS and peak urinary flow rates at 12 months, the main efficacy parameters of interest. However, there were differences regarding safety parameters. Time to catheter removal or catheterization time was evaluated in four pooled analyses. All four favored bipolar TURP; however, the differences in the effect estimate were highly variable as was the degree of heterogeneity. Length of stay and dilutional hyponatremia both favored bipolar TURP; however, there was close to 98% heterogeneity in each of the meta-analyses that evaluated these outcomes. Pooled data from Mamoulakis (2009), Burke (2010), Tang (2014), and Omar (2014) all supported that TUR syndrome occurred less frequently in the group that received bipolar TURP.219-222

Risk reduction for clot retention generally favored bipolar TURP. Bleeding and drops in hemoglobin seem to favor bipolar TURP but with a relatively high degree of heterogeneity in both meta-analyses. Need for blood transfusion post-operatively seems to favor bipolar TURP, although two out of six meta-analyses revealed no statistical significance.

The findings of the meta-analyses and systematic reviews allow the following conclusions:

  * Since there are no differences in efficacy, it is reasonable to compare surgical interventions in this Guideline document with either monopolar or bipolar TURP series regarding efficacy measures.
  * Since the main difference between monopolar and bipolar TURP is regarding TUR syndrome, which is unique to TURP and no other treatment, safety parameters other than TUR syndrome can also be compared between surgical interventions and monopolar and bipolar TURP.
  * The reduced risk of hyponatremia and TUR syndrome allows for longer resection times; therefore, bipolar TURP may be used in larger glands compared to monopolar TURP.
  * Since not all hospitals have bipolar TURP equipment available, it is left to the surgeon's discretion and level of experience as to which type of TURP energy is used.



For the remainder of this document the reader should assume that all efficacy comparisons between surgical interventions and TURP make no difference as to what type of energy was used for the TURP comparator arm(s).

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####  Simple Prostatectomy 

#### Guideline Statement 30

******Open, laparoscopic, or robotic assisted prostatectomy should be considered as treatment options by clinicians, depending on their expertise with these techniques, only in patients with large to very large prostates. (_Moderate Recommendation; Evidence Level: Grade C_)**

Discussion

×

#### Discussion

Landmark studies done in the 1990s showed that the risk of complications (e.g., bleeding, transfusion, hyponatremia, TURP syndrome, death) following monopolar TURP using sorbitol, mannitol, glycine, or a combination or mixture of such solutions, increase with increasing prostate size and increased duration of resection.223 These studies lead to recommended resection time limits of 60 or 90 minutes, and alternate therapies were employed for prostates that could not be adequately resected within that time frame.

Bipolar TURP technology using 0.9% NaCl solution has substantially improved the safety of TURP by virtually eliminating hyponatremia and significantly reducing the risk for TURP syndrome, bleeding, and transfusions, as discussed in Guideline Statement 28. As a result, bipolar TURP allows the resection of larger glands over longer periods of time without increasing the risks of the feared TURP complications.218 The experience and skill of the surgeon determines how large of a prostate can be addressed with this technology, and for many this includes glands up to 100cc, or even larger.

Before the introduction of bipolar TURP, large and/or very large adenomas were enucleated via open simple prostatectomy (OSP) using the transvesical or retropubic (Millin) approaches. Three RCTs (n=433) compared OSP techniques to TURP.224-226 Three trials used an open standard transvesical approach. Two trials reported significant differences in maximum urine flow at 12 months favoring OSP, while one trial found no difference between the groups. Need for blood transfusions were similar between groups (RR: 1.2; 95%CI: 0.4, 3.4). Need for reoperation as reported in 2 trials was lower in the OSP group compared to TURP (RR: 0.1; 95%CI: 0.01, 0.8). Long-term results for mean change in IPSS were not reported.

During widespread introduction of laparoscopic techniques into urologic surgery, approaches for laparoscopic simple prostatectomy/enucleation (LSP) were developed and favorable outcomes have been reported comparing LSP versus TURP227 and LSP versus OSP.228-233

As with most other pure laparoscopic surgical techniques in urology, the LSP has nowadays been more or less replaced by robotic-assisted laparoscopic simple prostatectomy (RASP). A recent systematic review and meta-analysis of trials comparing minimally invasive simple prostatectomies versus OSP234 found that RASP had similar efficacy in terms of symptom and flowrate improvement, but shorter catheterization time, length of stay, lower transfusion rates and lower complication rates overall.235-237 Independent of specific technique, laparoscopic and robotic simple prostatectomy are effective and safe procedures for large to very large glands.238

Finally, the introduction of the single port I robot has prompted some to use this technology for simple prostatectomy as well. One study has shown that with this approach, efficacy is maintained, while postoperative narcotic use is reduced.239

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####  Transurethral Incision of the Prostate (TUIP) 

#### Guideline Statement 31

******TUIP should be offered as an option for patients with prostates ≤30g for the surgical treatment of LUTS/BPH. (_Moderate Recommendation; Evidence Level: Grade B_)**

Discussion

×

#### Discussion

TUIP has been used to treat small prostates, usually defined as ≤30g, for many decades. In past updates of the AUA and other guidelines, many prospective cohort trials were analyzed, and adequate results were reported in terms of IPSS and Qmax changes. A meta-analysis comparing TUIP with TURP after a minimum follow-up of 6 months identified a lower rate of RE (18.2% versus 65.4%) and need for blood transfusion (0.4% versus 8.6%) as the key advantages of TUIP versus TURP.240

For the search period of this Guideline, 1 RCT (n=86, data reported for 80 completers) conducted in Egypt with 4-year follow-up comparing TUIP to TURP in men with small prostates (≤30g) was identified.42 Mean age of the participants was 65 years, baseline IPSS and prostate size were 19 and 28g, respectively. In these men, long-term mean change from baseline in IPSS was similar between the TUIP and TURP groups (WMD: 0.5; 9%CI: -0.2, 1.2), as was the need for reoperation and blood transfusion. In terms of sexual side effects, ED was reported for 8% of TUIP participants compared to 20% for TURP participations, though this difference was not significant (RR: 0.4; 95%CI: 0.1, 1.3). In contrast, there was a significant difference in reports of RE with a total of 30 participants experiencing RE (9 in the TUIP arm and 21 in the TURP arm).

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####  Transurethral Vaporization of the Prostate (TUVP) 

#### Guideline Statement 32

******Bipolar TUVP may be offered as an option to patients for the treatment of LUTS/BPH. (_Conditional Recommendation; Evidence Level: Grade B_)**

Discussion

×

#### Discussion

TUVP of the prostate is a technical electrosurgical modification of the standard TURP. TUVP can utilize a variety of energy delivery surfaces including a spherical rolling electrode (rollerball), grooved roller electrode (vaportrode), loop electrode, or hemi-spherical/oval mushroom electrode (button), amongst others. TUVP typically uses saline and is powered with a bipolar energy source. Compared to traditional resection loops, the various TUVP designs aspire to improve upon tissue visualization, blood loss, resection speed and patient morbidity.

Fourteen RCTs evaluating 1,828 participants compared bipolar TUVP with TURP.226, 241-259 Mean age among participants was 67 years (range 56 to 70). Mean baseline IPSS was 23 (range 18 to 27) and mean prostate volume was 51 mL (range 36 to 65 mL). Length of follow-up ranged from 3 months to 10.1 years. Overall, outcomes were similar in both groups for long-term response to treatment based on varying definitions using the IPSS; mean change in IPSS through 7 years; need for reoperation; and urinary incontinence. However, need for blood transfusion was lower for TUVP compared with TURP (<1% versus 4%; RR: 0.20; 95%CI: 0.08, 0.52).

Six RCTs (n=601) compared effectiveness of TUVP and bipolar TURP.43-48 Mean age was 66 years (range 60 to 69), baseline IPSS was 21 (range 18 to 24), and mean prostate volume was 56mL (range 32 to 64). Data were insufficient to compare IPSS changes. However, TUVP showed similar need for reoperation (RR: 1.5; 95%CI: 0.6, 3.9) and incontinence rates (RR: 0.9; 95%CI: 0.4, 2.1) as well as need for blood transfusion (RR: 0.6; 95%CI: 0.3, 1.4). A newer RCT [5.7] did compare clinical outcomes. In this study of 89 men with prostates greater than 40g and IPSS greater than 18, the mean prostate size was 59g in the TUVP arm and 58g in the bipolar TURP arm. At 9 months follow-up, there was no difference in change of IPSS (6.9 vs 5.2), max flow rate (18.3 vs 19.1 ml/sec), or prostate volume (31.8 vs 30.6 g). While this study did not report on reoperation rates, it did report a significantly higher of post-operative morbidity at 9 months in the TUVP group (29% vs 2% Clavien I), significantly higher rates of hematuria with clots at 4 weeks (9% vs 0%) and significantly higher rate of urethral strictures in TUVP groups at 6 months (11% vs 0%).

There are several centers worldwide performing Transurethral Vapor Enucleation of the Prostate (TUEVP). Like any enucleation surgery, the skill set required to safely and adequately apply this approach is very different than either vaporization or vaporesection techniques. There is a paucity of literature that meets the criteria and comparison group for this Guideline; as such, to include this approach into recommendations for TUVP would be premature at this time.

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####  Photoselective Vaporization of the Prostate (PVP) 

#### Guideline Statement 33

******PVP should be offered as an option using 120W or 180W platforms for the treatment of LUTS/BPH. (_Moderate Recommendation; Evidence Level: Grade B_)**

Discussion

×

#### Discussion

PVP is a transurethral form of treatment that utilizes a 600-micron side firing laser fiber in a noncontact mode. The laser wavelength is 532nm, which is preferentially absorbed by hemoglobin, resulting primarily in tissue ablation/vaporization with a thin layer of underlying coagulation that provides hemostasis. The procedure is generally performed with saline irrigation, reducing the possibility of TUR syndrome that can occur with non-ionic irrigation. The goal of the procedure is to vaporize the prostate adenoma sequentially outwards until the surgical capsule is exposed and a defect is created within the prostate parenchyma through which the patient may void.

A substantial collection of data has been published on PVP since the last publication of this Guideline. As part of this review, RCTs of PVP versus TURP were identified and examined for the 80W,260-268 120W,269-278 and 180w platforms.49, 50, 279 However, given the lack of availability of the 80W platform and the superior outcomes encountered with the higher powered lasers, clinicians performing PVP should utilize either the 120W or 180W options. The GOLIATH study (n=269) [5.33,] an RCT comparing PVP to monopolar or bipolar TURP, reported that PVP and TURP are essentially equivalent with respect to change in IPSS (6.9 vs 5.9) and maximum flow rate (21.6 vs 22.9) at 24-months post operatively.50

The Panel noted that PVP may be less efficacious for larger volume prostates and that patient expectations should be aligned accordingly. While the GOLIATH trial excluded patients with prostate volumes > 80g,263 a recent RCT randomized men with prostate sizes of 80-150g (average 105g) to PVP versus TURP versus HOLEP and found similar efficacy with regards to IPSS; however, PVP had a retreatment rate of 27% at three years of follow-up.51-53 Additionally, the need for a blood transfusion was lower for PVP compared to TURP; as such, PVP may be preferential for medically complicated patients on anticoagulation. This is further detailed in the section on medically complicated patients.

While other laser technologies can be utilized for laser ablation/vaporization of the prostate, some of these are considered legacy techniques and more are used for hybrid techniques such as laser vaporesection. This includes legacy technologies such as Nd:YAG laser ablation, which is preferentially absorbed by hemoglobin and has a depth of penetration of approximately 1 cm. This laser was used in the 1990's but fell out of favor secondary to side effects and high reoperation rates. It has recently had a resurgence, but data are lacking to support its routine use. Other lasers, such as various diode wavelengths, are also available on the market. Diode lasers are absorbed by hemoglobin and water. Like Nd:YAG, the depth of penetration is deeper than PVP. Clinicians should be aware that use of lasers for prostate surgery can lead to significant delivery of energy to the irrigating fluid, thereby increasing the temperature of the irrigant. High-powered and/or continuous lasers are at higher risk for temperature increases. Surgeons are advised to use continuous irrigation, occasionally test the temperature of the efflux, and consider whether a fluid warmer should be avoided. Overheated irrigant can cause thermal injury to any tissue that is subsequently exposed to the fluid and thermal injuries to the bladder have been reported after endoscopic prostate surgery.

Thulium laser vaporesection of the prostate is a combination of vaporization and resection. This technique was compared to TURP in a large (n=410) multicenter RCT.280 Both techniques had similar change in IPSS (6.3 for TURP vs 6.2) at 12 months post-operatively but significantly better improvement in maximum flow rate in the TURP arm (23.2 vs 20.2 mL/sec). There was no change in postoperative morbidity including bleeding, clot retention, transurethral resection syndrome, urethral stricture, or UTIs.

Laser vapo-enucleation, another hybrid technique, using a 180W 532 nm laser was compared to bipolar TURP in a study of 124 men with prostate size between 80 and 150 mL.53 At 36-months post-operatively, there was no differences in IPSS or maximum flow rate between the two techniques. There was also no difference among arms in post-operative UTI, bladder neck contracture, or need for additional therapy at 36 months. There was a significantly lower rate of blood transfusion in the laser arm compared to the TURP arm (0% vs 7%).

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####  Prostatic Urethral Lift (PUL) 

#### Guideline Statement 34

**PUL should be considered as a treatment option for patients with LUTS/BPH provided prostate volume 30-80g and verified absence of an obstructive middle lobe. (_Moderate Recommendation; Evidence Level: Grade C_)**

Discussion

×

#### Discussion

PUL alters prostate anatomy without ablating tissue via the placement of transprostatic suture implants. The implants pull the lumen of the prostatic urethra towards the capsule and widen the prostatic urethral lumen. The urethral side of the implant epithelializes within 12 months. Histopathologic analysis of tissue obtained after PUL demonstrates a benign response to the implant. No significant changes have been noted in PSA after implantation.

The L.I.F.T study compared PUL to SHAM54 in 206 patients. It excluded patients with a prostate <30g, > 80g or an obstructive middle lobe. The primary outcome was urinary symptom score. The mean change from baseline IPSS (MD: -5.2; 95%CI: -7.45, -2.95) and improvement in IPSS-QoL (MD: 1.2; 95%CI: 1.7, -0.7) favored PUL. The mean change in Qmax at 3 months was higher for those who underwent PUL (4.3mL/s) compared to SHAM (2.0mL/s), P=.005. Of the participants randomized to PUL, five-year follow-up data demonstrated slight decreases in mean IPSS and QoL scores; however, both remained significantly improved from baseline.

The BPH6 Study was a non-inferiority RCT of 80 patients comparing PUL to TURP. It assessed symptom improvement, sexual health, and other outcomes. A lower proportion of individuals in the PUL group responded to treatment at 12 months follow-up compared to TURP as measured by the IPSS reduction goal of ≥30% (73% versus 91%; P=.05).55 At 24 months follow-up, the mean difference between PUL and TURP was 6.1 points (95%CI: 2.2, 10.0) favoring TURP; however, changes in IPSS-QoL were similar between groups at all follow-up intervals. Qmax was significantly lower in participants allocated to PUL at all follow-up intervals.

Clinicians should verify prostate morphology and volume as previously detailed in the Evaluation and Preoperative Testing section. The Panel limited this guideline statement to include patients with a prostate lacking an obstructive middle lobe, consistent with the L.I.F.T. study criteria. The Panel identified an observational cohort study (n=45 patients) observing improvements in urinary and sexual health outcomes from baseline in patients with an obstructive middle lobe following PUL. This study was excluded from formal efficacy analysis because it was a nonrandomized cohort study utilizing historic controls rather than an RCT.281

Since the last amendment, there have been retrospective chart reviews evaluating a small number of patients with prostate sizes between 81-100mL. The Panel recognizes that many devices do not necessarily lack efficacy in prostates below or above the size ranges stipulated in the Statements, but there is insufficient evidence to make formal recommendations beyond those sizes identified.

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####  Guideline Statement 35 

**PUL may be offered as a treatment option to eligible patients who desire preservation of erectile and ejaculatory function. (_Conditional Recommendation; Evidence Level: Grade C_) **

Discussion

×

#### Discussion

Compared to many other surgical interventions, PUL has a higher likelihood of preserving sexual function.282 Woo et al. demonstrated that the sexual function of men with normal or moderate ED at baseline was unaffected, and those with severe ED reported modest improvement. There was no evidence of de novo EjD or ED over the course of the study. Ejaculatory bother improved by 40% at 1 year (p<0.001), while intensity of ejaculation and amount of ejaculate improved by 23% and 22%, respectively (p<0.001). This larger study verified the findings previously published in initial testing.283

In the BPH6 Study, no participants in the PUL group experienced adverse events related to sexual function.55 In comparison, ED and RE occurred in 9% and 20%, respectively, of the participants in the TURP group. While measures of EF using the Sexual Health Inventory for Men (SHIM) was similar between groups at all time points, ejaculatory function based on Male Sexual Health Questionnaire for EjD (MSHQ-EjD) score was better in the PUL group, with TURP participants experiencing declines from month one onward. MSHQ-EjD bother scores were similar throughout the 24-month follow-up. The L.I.F.T. study showed non-significant differences in sexual function between PUL and SHAM groups as measured via SHIM, IIEF-5, MSHQ-EjD function, and MSHQ-EjD bother. In men concerned about new onset of ED and/or EjD, PUL likely does not pose additional risk.

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####  Water Vapor Thermal Therapy (WVTT) 

#### Guideline Statement 36

******WVTT should be considered as a treatment option for patients with LUTS/BPH provided prostate volume 30-80g. (_Moderate Recommendation; Evidence Level: Grade C_)**

Discussion

×

#### Discussion

WVTT utilizes convective radiofrequency to create stored thermal energy in the form of steam, which is delivered transurethrally via a specialized device into the transition zone. The steam travels through the transition zone, denaturing tissue and thereby ablating the adenoma to create an opening. A double-blind RCT56-58 (n=197) compared WVTT (also referred to as transurethral destruction of prostate tissue by radiofrequency generated water thermotherapy) with SHAM. Mean age of study participants was 63 years. Patients had a mean baseline IPSS of 22 and a mean prostate volume of 45g. The study excluded men with prostate volume < 30g and > 80g and did not exclude men with obstructing middle lobes or median bars.

Response to treatment through three months, based on an improvement in IPSS of ≥30% or ≥8 points, was significantly greater in the WVTT group (74%) compared to the SHAM group (31%) (RR: 2.4; 95%CI: 1.6, 3.5). Mean changes from baseline in IPSS and IPSS-QoL at three months were greater in the WVTT group compared to the SHAM group with a MDD of >3 points (MD: -6.9; 95%CI: -9.1, -4.8).

Three-year results showed sustained improvements for the IPSS IPSS-QoL, and Qmax, with scores remaining significantly improved from baseline;59 Qmax improvement was > 50% from 3 to 24 months and 39% at 36 months.12 At 36 months in the intent-to-treat population of the original 136 participants, mean change from baseline in IPSS was -11.0 points and the mean score was 10.4 points, representing a 50% improvement from baseline. Mean IPSS-QoL was improved from baseline by 49% at 3 years.

Five-year results showed mean change in IPSS from baseline through 60 months was 15.1 points for the WVTT group compared with 13.2 points for the TURP group (MD 1.9 points [95% CI -1.41 to 5.21]).284 At 60 months, improvements in the IPSS-QoL were similar with a mean score of 1.6 in both treatment arms. Maximum flow rates increased at one month after treatment in both groups and increases were maintained at 60 months.

Significant improvement of LUTS was observed through five-years in the treatment group for WVTT.284 Results showed IPSS was reduced 48%, QoL increased 45%, and maximum flow rate improved 44%.

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####  Guideline Statement 37 

**WVTT may be offered as a treatment option to eligible patients who desire preservation of erectile and ejaculatory function. (_Conditional Recommendation; Evidence Level: Grade C_)**

Discussion

×

#### Discussion

Compared to many other surgical interventions, WVTT has a higher likelihood of preserving sexual function. In the RCT comparing WVTT to SHAM, the original 136 patients randomized to WVTT are expected to be followed for five years.57 Few harms occurred in the WVTT group between months 3 and 12. A decrease in ejaculatory volume was reported by 2% of participants.56-59  At 36 months, no de novo ED was reported, but dysuria was reported by 1% of participants.56-59  At 48 months, there was a significant change in IIEF-EF scores compared to baseline (P=.03), but there was not a significant change at the other follow-up intervals.60

Function scores associated with ejaculation, assessed by the MSHQ-EjD, were significantly improved at 36 and 48 months following treatment (P=.005 and P=.003) but not at 12 and 24 months.59 Bother scores associated with ejaculation, assessed by the MSHQ-EjD, were significantly improved at 12, 24, and 36 months but not at 48 months following treatment.60

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####  Laser Enucleation 

#### Guideline Statement 38

******Holmium laser enucleation of the prostate (HoLEP) or thulium laser enucleation of the prostate (ThuLEP) should be considered as an option, depending on the clinician 's expertise with these techniques, as prostate size-independent options for the treatment of LUTS/BPH. (_Moderate Recommendation; Evidence Level: Grade B_)**

Discussion

×

#### Discussion

Due to the chromophore of water and minimal tissue depth penetration with both holmium and thulium (0.4mm for holmium, 0.2 mm for thulium), these two lasers achieve rapid vaporization and coagulation of tissue without the disadvantage of deep tissue penetration. They have better coagulative properties in tissue than either monopolar or bipolar TURP, and combined with their superficial penetration, both thulium and holmium are appropriate for endoscopic enucleation.285

HoLEP and ThuLEP have similar outcomes when compared to TURP for the treatment of symptomatic BPH as measured by IPSS and IPSS-QoL outcomes. Based on seven studies reporting long-term follow-up comparing HoLEP to TURP, ranging from 12 to 92 months, mean changes in IPSS (approximately -19) between groups favored HoLEP, but they did not meet the MDD of 3 points (WMD: -1.3; 95%CI: -2.3, -0.3). At the intermediate follow-up, the WMD was -0.7 (95%CI: -1.6, -0.1). Mean difference in IPSS at the short-term was different (favoring HoLEP), but the difference did not achieve the MDD of 3 points. Eleven studies reported quality of life. Mean differences between groups were similar at all follow-up points. Mean changes in QOL scores between groups were similar at the intermediate-and short-term follow-up. Based on results from two long-term trials, the mean difference in QoL between HoLEP and TURP was -0.1 (95%CI: -0.05, 0.25).53, 62, 63, 286-291

Qmax at last follow-up after HoLEP compared to TURP is generally similar. Of the 13 studies reporting Qmax, 9 found the HoLEP and TURP groups to be similar.62, 63, 288-290 61, 291-295  Three studies, however, found significantly higher Qmax in the HoLEP groups.286, 287, 296

Five HoLEP studies enrolled men who had prostates of 75g or greater.286, 287, 297-299 At follow-ups ranging from 12 to 36 months, HoLEP resulted in little or no difference in IPSS compared to TURP or another comparator (k=5; 2 studies showing an improvement with HoLEP and 3 showing no difference).286, 287, 297-299 There was no difference in IPSS-QoL (k=4).286, 297-299 In the 4 studies reporting need for blood transfusion no significant differences between HoLEP and TURP or another comparator were reported although studies were likely underpowered to detect these infrequent events (a total of 0 events in the HoLEP group vs 9 in the TURP or other comparator group; total N=465).286, 287, 297, 299 Of the 4 studies reporting incontinence, none reported a significant difference in incidence between the HoLEP and TURP or other comparator groups. Significant heterogeneity between most identified studies limits confidence of outcomes in pooled analysis of ThuLEP versus TURP. However, ten RCTs (n=1181),64-66, 300-307 two CCTs (n=159),308, 309 and three trials53, 287, 299 reported long-term results in IPSS reduction (mean change approximately -15), ranging from 18 to 60 months (WMD: 0.4 points; 95%CI: -0.9, 1.6). There was no difference in mean reduction in IPSS within each group (- 15.1) or QoL outcomes (mean change approximately -2.0). At long-term follow-up, the mean difference was -0.3 (95%CI: -0.4, 0.9). Qmax after ThuLEP and TURP were similar at three months,65, 66, 304, 305 12 months, 291, 308, 309 18 months,303 48 months,308 and five-year follow-up.302 Prostate volume was reported in one study with significantly lower prostate volume post-procedure in the ThuLEP group (mean 11.7g) compared to TURP (mean: 18.3g);33 while another study reported mean resected volumes of 51g in the ThuLEP group and 49g in the TURP group.30

Two studies reported IIEF scores which were similar between the thulium laser and TURP groups at 18 months27 and 12 months.24 RE was reported in five studies with all reporting similar outcomes for the thulium laser and TURP groups.19-22, 33 One study reported higher incidence of ED after TURP (44%) compared to ThuLEP (17%).31

There have been three additional studies reporting other enucleating procedures.310-312 One procedure on bipolar enucleation of the prostate and resection of the prostate (n=240)310, plasma button transurethral vapor enucleation of the prostate (n=101)311 and monopolar enucleation of the prostate (n-134).312 All three studies showed improvement in IPSS and IPSS-QoL in both groups, but there was no significant difference between the individual enucleating procedure and their comparator. Maximum flow rates also improved in all the studies, with only one study showing bipolar enucleation to have slightly higher Qmax compared to TURP (24.9 vs 20.1, P=.03). When reported there was no significant difference in the need for blood transfusions between enucleating and its comparator. There was no difference in erectile dysfunction or urinary incontinence between the individual enucleation technique and its comparator.

In addition to HoLEP and ThuLEP, other laser modalities have been utilized for enucleation - namely diode and Greenlight. Diode lasers used in urology have variable wavelengths and several have been utilized for enucleation, but only by a handful of surgeons with few studies. Diode lasers have absorption by both water and hemoglobin. Greenlight has gained in popularity and more studies have been published since it was first described. In addition to laser energy, electrosurgical, and even "cold" energy free, transurethral surgical tools have been utilized for enucleating. Published studies show promise with these modalities in the hands of surgeons comfortable with the technique of endoscopic enucleation. Currently, the studies are too few to make guidelines recommendations. However, endoscopic enucleation, particularly with laser energy, has clearly become an accepted modality; as such, further applications and support in guidelines are likely in the future.

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####  Robotic Waterjet Treatment (RWT) 

#### Guideline Statement 39

******Robotic waterjet treatment (RWT) may be offered as a treatment option to patients with LUTS/BPH provided prostate volume 30-80g. (_Conditional Recommendation; Evidence Level: Grade C_) **

Discussion

×

#### Discussion

RWT surgery utilizes a robotic handpiece, console, and conformal planning unit (CPU). The technique is not in the MIST category as patients must undergo general anesthesia. The resection of the prostate is performed using a water jet from a transurethrally placed robotic handpiece. Pre-treatment transrectal ultrasound is used to map out the specific region of the prostate to be resected with a particular focus on limiting resection in the area of the vermontanum. It is also used to monitor tissue resection in real time during the procedure. After completion of the resection, electro-cautery/thermal energy via a standard cystoscope/resectoscope, use of a tamponade balloon catheter, or traction from a 3-way catheter balloon is used to obtain hemostasis.

Several publications from a low ROB RCT (n = 181) assessing RWT were evaluable by the Panel.68, 69, 313, 314 Other recent publications evaluating RWT were excluded from analysis because of their cohort (not comparative) study design.315 The trial utilized standard inclusion/exclusion criteria limiting participants to prostate sizes between 30-80g.68, 69, 313, 314, 316 Treatment response through 12, 24, 36, and 60 months, defined as at least a 5-point improvement in IPSS, was similar for RWT and TURP (quality of evidence was rated moderate for long-term treatment response for RWT compared to TURP). Mean improvement in LUTS based on the IPSS through 12, 24, 36, and 60 months was similar for RWT and TURP (quality of evidence was rated moderate for IPSS mean-change from baseline for RWT compared to TURP). Mean improvement in QoL based on the IPSS-QoL through 12, 24, 36, and 60 months was similar for RWT and TURP (quality of evidence was rated moderate for long-term mean improvement in QoL based on the IPSS-QoL for RWT compared to TURP).68, 69, 313, 314 At 12 months follow-up, maximum flow rate increased similarly in the RWT group compared to TURP, 10.3 versus 10.6 mL/s (P=.86), respectively.68, 313, 314 At 24 months, maximum flow rate for RWT and TURP was 11.2 mL/s and 8.6 mL/s respectively (P=.19),at 36 months and this was maintained at 60 months.316

At 3 months, RWT resulted in fewer harms classified as Clavien-Dindo grade ≥2 compared to TURP, 26% versus 42%, P=.015.68, 313 Also at 3 months, reduction in prostate volume was significantly less with RWT (31%) compared to TURP (44%) (P=.007).68, 313  Additionally, rates of RE were higher (P=.002) with TURP (23%) compared to RWT (6%).68, 313 At three years, post-operative anejaculation was noted less frequently in the RWT group (11%) compared to the TURP group (29%), P<.05. Other harms classified as Clavien-Dindo grades 1-4 occurred at similar rates in both groups, including bladder spasms, bleeding, dysuria, pain, and urethral damage. No deaths were reported. The authors reported the need for additional therapy at 60 months follow-up in 6% of participants after RWT and 12% of participants after TURP316; however the need for additional surgical therapy was 5% of participants after RWT compared to 2% after TURP.

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####  Prostate Artery Embolization (PAE) 

#### Guideline Statement 40

**PAE may be offered for the treatment of LUTS/BPH. PAE should be performed by clinicians trained in this interventional radiology procedure following a discussion of the potential risks and benefits. (_Conditional Recommendation: Evidence level: Grade C_)**

Discussion

×

#### Discussion

One RCT (n= 80) was identified comparing PAE to SHAM (PAE procedure with no embolization).317 This was a single blind trial that reported outcomes at six months with no long-term data available. After six months the patients randomized to the SHAM arm (n=38) were crossed over to receive PAE and followed for six months. Males over 45 years old were included in the study if they had severe LUTS defined as an IPSS ≥20 and a QoL score of ≥3 after a minimum of 6-mo treatment with medical therapy, a Qmax less than 12 mL/s and a prostate volume over 40cc. Patients were excluded if they had a CT angiography showing the prostatic arteries were not amenable to PAE or if they had prior surgical or invasive treatment on their prostate. The exclusion criteria were extensive, men were also excluded if they had a history of prostate or bladder cancer, neurogenic lower urinary tract dysfunction, history of large bladder diverticula or stone, detrusor underactivity/failure, prior history of urinary retention or an identified bleeding disorder. The PAE procedure was done with 300-500 μm microspheres. The procedure time was 71.3 ± 18.1 min, fluoroscopy time 19.4 ± 9.71 min, and a radiation dose 247.9 ± 153.8 Gy.cm2.

The proportion of responders was not reported. PAE may have improved IPSS scores compared to SHAM (MD -13.2 points [95% CI -16.2 to -10.2]; moderate certainty of evidence). Mean changes in IPSS-QoL also favored the PAE group (MD -2.0 points [95% CI -2.5 to -1.5], moderate certainty of evidence) and achieved the minimally detectable difference (MDD) of one point. At six months, greater mean improvement in flow rates (Qmax) was achieved with PAE compared with SHAM (6.8 mL/s vs. 2.8 mL/s). Mean prostate volumes were significantly reduced in the PAE group compared with the SHAM group (-17.6g vs. -0.1g). Hematuria, ecchymosis, urethral pain and dysuria were the most common adverse events reported. One patient in the initially randomized to the SHAM group had hematuria after their cross-over PAE due to expulsion of small prostate fragments that caused urinary retention that required treatment by TURP. No need for blood transfusion or reoperation was reported.

Five RCTs (n=352) were identified comparing PAE to TURP.318-323 Two trials reported outcomes up to two years,319, 321 two up to 12318, 322 and one through six months.323 There was substantial heterogeneity between trials; therefore, pooled results must be interpreted with caution. Definitions of and outcomes for subjective symptom response varied substantially between trials. One trial reported the proportion of responders, defined as achieving an IPSS score ≤8 points and/or a QoL ≤3 points, was similar between the PAE and TURP groups (RR: 0.9; 95%CI: 0.7, 1.1; low quality of evidence for IPSS score change for PAE compared to TURP).318 Success through 12 months was reported for 87% of the PAE participants compared with 100% in the TURP group. Results from another trial found the mean change in IPSS from baseline through two years was similar between groups (MD 0.7 points [95% CI -1.3 to 2.7]319 while results at year two from one trial favored TURP compared to PAE (MD 2.9 points [95% CI 0.04 to 5.72]; very low certainty of evidence).321 Overall, while results at intermediate term follow-up (>3 to ≤12 months) were similar between groups we are very uncertain of the effect (WMD 2.3 points [95% CI -3.2 to 7.8; very low certainty of evidence).318, 319, 323 One of the trials (n=30) reported substantially greater improvement in symptoms with TURP compared with PAE (MD 9 points [95% CI 4.6 to 13.1]),318 and the other (n=107) reported no significant difference between the groups at three and 12 months.319 Pooled results from two trials reporting data at three months showed no statistically significant difference between groups (WMD 3.4 points [95% CI 0.0 to 6.8]; I2 = 70%).

Mean changes in IPSS-QoL followed a similar pattern to the findings for mean change in IPSS scores. Long-term (24 months), one trial found mean change in QoL scores from baseline was similar between groups (MD 0.0 points [95% CI -0.3 to 0.3]319 while the other long-term trial reported greater improvement with TURP (MD 0.99 points [95% CI 0.3 to 1.7]),321 with overall findings having very low certainty of evidence). Overall, results at intermediate term follow-up were also similar between groups though we are very uncertain of the results (WMD 0.1 [95% CI -0.8 to 1.1]; very low certainty of evidence).318, 319, 323 There was substantial heterogeneity between trials (I2 = 86%) with the smallest trial (n=30) reporting greater improvement with TURP318 and the other trials reporting no significant difference between the groups.

Results also differed between the trials regarding improvements in Qmax. Three trials, two intermediate-term and one short-term, reported lower flow rates with PAE compared with TURP.318, 321, 323 In contrast, the other trial reported peak urine flow rates were similar between groups for the intermediate- (12 months) and long-term (24 months) follow-ups.319 Flow rates were approximately 22 mL/s in both groups at 24 months. Results from the other trial with long-term results reported much greater mean improvement in flow with TURP compared to PAE, 10.2 mL/s versus 3.9 ml/s, respectively (P<.001).321 PAE was not as effective in reducing prostate volumes compared with TURP. Mean prostate volumes were significantly higher in the PAE group compared with the TURP group at all follow-up time points.318, 319, 322, 323 Two studies found mean prostate size decreased from average (>30 to <80 mL) to small (≤30 mL) among participants in the TURP group at short-, intermediate-, and long-term follow up.319 

Additionally, for the portion of patient (39/82 patients) who underwent post-PAE urodynamics, the 12-week trial reported PAE was not as effective in reducing measures of BOO, indicated by change in detrusor pressure at maximum flow rate, compared with TURP, -17.2 vs. -41.1 cmH2O (P=.002).320 Postoperatively, 56% of PAE patients were considered less obstructed by these measures compared with 93% of TURP (P=.003).320

Overall need for a blood transfusion was infrequent; reported for two TURP participants and none receiving PAE (Peto OR 0.13 [95% CI 0.01 to 2.15]; very low certainty of evidence).318, 319, 323 Urinary incontinence was lower with PAE compared to TURP (RR 0.13 [95%CI 0.02, 0.70]).318, 319, 322 Need for reoperation was greater in the PAE group (17 participants) compared with the TURP group (seven participants) (RR 2.4 [95% CI 1.1 to 5.5]; low certainty of evidence).318, 319 Two trials found incidences of sexual dysfunction to be higher with TURP compared with PAE. One trial reported all 15 TURP participants experienced retrograde ejaculation while no cases were reported among PAE participants.318 One trial found incidence of ejaculatory dysfunction was lower with PAE (56%) compared with TURP (84%) after 12 weeks (RR 0.67 [95%CI 0.45 to 0.98).320, 321 One trial reported a higher incidence of acute urinary retention requiring re-catheterization in the PAE group (26%) versus the TURP group 6%, P=.004).319 This trial also found adverse events were half as frequent after PAE (n=36) compared to TURP (n=70), P=.003. Additionally, more cases of hematuria, urinary retention, UTI, and strictures were found after TURP.318-320 Postoperative incidences of clot retention and strictures were infrequent.319, 320One incidence of TUR syndrome was reported.319

As with all of the interventions in this Guideline, the Panel carefully weighed the potential benefits and harms of PAE. The panel was unable to find substantial evidence to recommend PAE over more widely available minimally-invasive therapies for the routine treatment of LUTS, but there is evidence showing a short-term benefit of PAE compared to observation in a very select patient population. PAE is a technically demanding procedure, averaging fluoroscopy times of up to 50 minutes and procedure times up to 2 hours.320 Attainment of proficiency involves a challenging learning curve for physicians who--while trained in the performance of endovascular interventions--may be less familiar with core concepts of BPH pathophysiology, diagnosis, treatment, and follow-up which is why the Panel recommends that these procedures are only performed by physicians specifically trained in this technique.320 The Panel recommends continued investigation of PAE through trials involve multi-disciplinary teams of urologists and radiologists focused on further defining specific indications, including but not limited to gross hematuria recalcitrant to other therapies (see further discussion under Statement 42).

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####  Temporary Implanted Prostatic Devices (TIPD) 

#### Guideline Statement 41

****

******TIPD may be offered as a treatment option for patients with LUTS/BPH provided prostate volume is between 25 and 75g and lack of obstructive median lobe. (_Expert Opinion_)**

Discussion

×

#### Discussion

One RCT conducted at 16 sites in the US and Canada, compared TIPD to SHAM. A total of 185 men with prostate volumes between 25 and 75g were randomized (128 to TIPD, 57 to SHAM). An improvement in the IPSS of at least 3 points at three months post-procedure was reported in 78.6% of the TIPD group and 60.0% of the SHAM group (RR 1.3 [95% CI 1.1 to 1.7]; P=.03).324 Mean change in IPSS at three months was 9.0 in the TIPD group and 6.6 in the SHAM group. This did not statistically significantly differ between groups (P=.06) and the mean change in IPSS did not achieve the minimally importance difference of at least three points. There was a statistically but not clinically meaningful difference in the short-term mean change in the IPSS Quality of Life score at three months with greater change in the TIPD group (mean difference 0.7 lower; 95%CI 1.31, 0.09).324 The responder analysis (IPSS improvement of 7 or more points) was performed at 12-months and showed a responder rate of 72.6% compared to 50% in the sham arm (p=0.48). Mean scores for the IIEF and the Sexual Health Inventory for Males (SHIM) did not differ significantly from the baseline at three months.325 Mean peak flow rate at three and 12 months was significantly improved (P<.0001) from baseline in the TIPD group but was not reported for the SHAM group. There were few related serious adverse events but more overall adverse events, within the first 30 days, in the TIPD group than the SHAM group (38.1% vs 17.5%). Need for additional surgery or initiation of medication for BPH in the first three months was similar between groups.324

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###  Hematuria 

####  Guideline Statement 42 

**After exclusion of other causes of hematuria, 5-ARIs may be an appropriate and effective treatment alternative in men with refractory hematuria presumably due to prostatic bleeding. (_Expert Opinion_)**

Discussion

×

#### Discussion

Refractory hematuria secondary to prostatic bleeding poses a challenging treatment dilemma for urologists and patients alike, particularly in the era of anticoagulation. Surgical interventions for symptomatic BPH are often used and have been described in the management approach.326 However, surgical intervention may not be desired depending on the ability to hold anticoagulation and/or the frailty of the patient. 

One of the early intraprostatic effects of finasteride has been the suppression of vascular endothelial growth factor (VEGF).19, 327-329 Initially anecdotally,330 and then in long-term follow-up studies331-333 it was noted that men with prostate-related bleeding (i.e., all other causes of hematuria had been excluded) responded to finasteride therapy with a reduction or cessation of such bleeding and a reduced likelihood of recurrent bleeding. A prospective study verified these observations.19 The role of short term use of finasteride to decrease perioperative bleeding in men undergoing TURP is less defined and is not considered to be a routine method of care.151 As options are often limited in men with troublesome or refractory bleeding of prostatic origin, the use of 5-ARIs has benefits with regard to bleeding events; however, patients should still be counseled on potential side effects.

The potential role of PAE in the management of refractory hematuria is evolving. Many of the studies include a small number of patients with various etiologies of hematuria. Nevertheless, the ability to both decrease prostate volume and decrease vascular inflow makes PAE a potential adjunct in management of refractory hematuria.334

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###  Medically Complicated Patients 

####  Guideline Statement 43 

**HoLEP, PVP** ,**and ThuLEP should be considered as treatment options in patients who are at higher risk of bleeding. (_Expert Opinion_)**

Discussion

×

#### Discussion

Multiple studies have shown that the need for a blood transfusion (either peri- or post-operatively) was significantly less likely with HoLEP and ThuLEP as compared to TURP (RR: 0.20; 95%CI: 0.08, 0.47) and (RR 0.4; 95%CI: 0.1, 0.9), respectively.44, 62, 289, 295, 300, 335 In addition, studies of holmium laser prostate surgery in patients maintained on anticoagulation therapy at time of surgery have supported a relatively low transfusion rate. In a 2013 retrospective review on a series of 125 patients treated with HoLEP (52 patients were on antithrombotic therapy at the time of surgery, and 73 patients were not), only 4 men (7.7%) in the antithrombotic group required a blood transfusion compared to none in the control group.336 A similar 2016 study compared 116 patients who required anticoagulation/antiplatelet therapy at the time of HoLEP to 1,558 patients who did not. Other than a slightly increased duration of bladder irrigation and hospital stay, the use of anticoagulation/antiplatelet therapy did not adversely affect outcomes.337 Lastly, a 2017 meta-analysis of patients on therapeutic anticoagulation/antiplatelet therapy when undergoing HoLEP supported that this approach can be performed safely on these patients, but the analysis stressed that there are limited data surrounding the class of direct oral anticoagulants and safety.338

While there are differences between wavelengths as well as the chromophore in which laser energy is absorbed (i.e., water, hemoglobin, pigment), in general, lasers have favorable hemostatic properties that treat bleeding more effectively than monopolar energy. Most lasers used in urology (532 nm, holmium, thulium) have superficial penetration and thermal diffusion depths that lead to the concentration of high-density energy in a superficial layer, thereby "sealing" vessels and creating shallow coagulation zones. Holmium and thulium both have similar wavelengths (holmium 2,140nm, thulium 2,013nm) and are absorbed by water. The major difference is that holmium is a pulsed laser while thulium is continuous, which impacts how quickly the temperature rises in the tissue. The decreased penetration depth of holmium and thulium as compared to monopolar energy leads to a more superficial area of ischemia and can reduce risk for delayed bleeding, as eschar sloughs approximately 7-14 days post procedure. During this timeframe, any anticoagulant therapy that may have been discontinued will have resumed and be in effect, thereby making the reduction in eschar a significant benefit.285, 337-342

The safety of thulium in anticoagulated patients has been reported in several publications. In one study of 56 patients (32 on aspirin, 8 on clopidogrel or clopidogrel plus aspirin, and 16 on phenprocoumon), 4 patients needed blood transfusions, and 4 patients required immediate reoperation. Given this high-risk group and despite the reported issues, the patients did well overall.343 Two other studies have described the feasibility of thulium laser for prostate surgery in anticoagulated patients and those bridged with low molecular weight heparin (LMWH). A 2013 study of 76 patients compared those on anticoagulant/antiplatelet therapy during surgery to those who were bridged with LMWH. There were no statistically significant variations in hemoglobin between the two groups.341

A similar more recent 2017 study of 103 patients revealed the drop in hemoglobin levels in the pre- and post-operative periods were significantly higher in the LMWH bridged group than those who remained on anticoagulant/antiplatelet therapy during surgery. Given that no cardiopulmonary adverse events occurred and bleeding was not problematic, the authors recommend abandoning LMWH bridging and continuing anticoagulant/antiplatelet therapy during thulium laser surgery.344

PVP is performed using the lithium triborate laser, which has a wavelength of 532 nm and a chromophore of hemoglobin. The depth of penetration with PVP is 0.8 mm. Multiple studies have found that PVP is safe and effective for patients who continue their anticoagulant/antiplatelet therapy, with negligible transfusion rates. However, surgeons should be aware that longer catheterization and irrigation with an increased rate of complications has been reported, and delayed bleeding is more pronounced in these patients.345-348 A 2017 study confirmed these findings in 59 of 373 patients undergoing PVP. Overall, Greenlight PVP with the 180W laser unit on patients therapeutic on heparin, warfarin, clopidogrel, dipyridamole, or new oral anticoagulant drugs revealed good safety outcomes.349 As expected, anticoagulated patients were older, had a higher American Society of Anesthesiologists (ASA) score than the control group and, although no patient required blood transfusion, there was a higher incidence of high-grade Clavien-Dindo events. Similar to other studies, the therapeutically anticoagulated group had a significantly longer length of hospital stay and duration of catheterization as compared to the controls. In support of the concept of 120W PVP use in anticoagulated patients, recent publications report that the need for a blood transfusion was lower for PVP with 120W compared to TURP.277, 278

For additional information on the use of anticoagulation and antiplatelet therapy in surgical patients, refer to the ICUD/AUA review on Anticoagulation and Antiplatelet Therapy in Urologic Practice.350

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###  FUTURE DIRECTIONS 

BPH and ensuing LUTS is a significant health issue affecting millions of men. There are enormous gaps in knowledge; therefore, there are also significant opportunities for discovery. Many unanswered questions exist, including but not limited to the role of inflammation, metabolic dysfunction, obesity, and environmental factors in etiology, as well as the role of behavior modification, self-management, and evolving therapeutic algorithms in both the prevention and progression of disease.

**Disease Etiology**

Currently, there are few animal and human tissue models for LUTS/BPH. This limits the ability and efforts to understand both pathogenesis and progression. More specifically, computational biology and genomic factors should be aimed toward understanding drivers of BPH and prostate growth and therapeutic targets.

LUTS are differentially bothersome. Moreover, qualitative rather than quantitative changes have not been well described. Enhanced metrics including bother, pain, and incontinence will need to be incorporated and evaluated.

**Addressing Healthcare Disparities and Cultural Competency**

In a seminal 2003 report, the Institute of Medicine (IOM) defined healthcare disparities as differences in the quality of healthcare not due to access-related factors, clinical needs, patient preferences, and appropriateness of intervention.351 There remains a paucity of data on racial and ethnic variations in LUTS/BPH prevalence and treatment, most notably in the Black and Latinx communities. Further study of this topic to address systemic biases in the LUTS/BPH care of these populations would substantially inform this Guideline and promote healthcare equity. So, too, would implementation and study of educational endeavors focused upon improving cultural competency among LUTS/BPH clinicians.

**Management of Nocturia**

The most prevalent and bothersome symptom of the LUTS is nocturia. The differential diagnosis of increased nighttime urination frequency/volumes and the role of sleep apnea is an area of great importance given that nocturia is also associated with increases in overall mortality. Due to the considerable burden of nocturia on QoL and a lack of effective management options, more funded research is needed. Nocturia is often multifactorial in origin and symptomatic of other medical problems, further complicating effective management. Nocturia, whether global, reduced bladder capacity, or mixed, is a unique symptom complex requiring special concern and judicious evaluation.

**Urodynamic Evaluation and Imaging**

The natural history and predictive ability of various urodynamic measures, such as flow rate and PVR, in regard to predicting patient reported outcomes (e.g., symptoms, QoL), and objective outcomes (e.g., peak flow, development of total retention, need for retreatment) is an area of great interest with substantial clinical and health care economic consequences.

Morphological aspects such as bladder wall thickness, degree of trabeculation, prostatic urethral angle, and intravesical prostatic protrusion can affect natural history, treatment response, and treatment options. Prostate imaging and other novel tests are areas of potentially beneficial and significant research.

**Development of a Patient-Centered Approach to Improve Adherence and Compliance**

While medications for LUTS attributed to BPH have become the mainstay of therapy, there is wide variability among prescribers with respect to treatment choice (i.e., class of drug, monotherapy versus combination therapy). In addition, appropriate and patient-centered therapeutic strategies continue to lag behind evidence-based medicine. In large part, this has led to poor adherence and compliance with various therapies. Several factors play a role including insurance coverage, type of medication, side effects of medication, race and availability of information technology. Finally, managing patient expectations is variable among prescribers. Use of technology, improved informatics, and coalescence of treatment strategies are opportunities to improve both short- and long-term safety and efficacy with medications. In addition, this could provide more uniform approaches to treatment success and failure and gateways to both minimally-invasive and surgical therapies.

**New Therapeutic Options**

There have been a number of new therapeutic options utilized for LUTS/BPH over the past few years. Despite the expansion of the treatment algorithm, the ceiling on medical therapy has not been well elucidated. The potential role of combination therapy and other routes of delivery are under investigation and remain to be defined. These include changes in dosing patterns (e.g., weekly, monthly). Moreover, many promising MISTs and surgical alternatives are in development including prostatic stents, temporary implantable prostatic devices (TIPD), drug eluting catheters, balloon dilation devices and transurethral prostatic split techniques to name a few. It is the hope of this Panel that further robust data will be available in the peer reviewed literature on these therapies to allow incorporation into future iterations of this Guideline. To guarantee that newer technologies genuinely deliver enhanced improvements and outcomes for patients, it is crucial to maintain an ongoing benchmarking process that consistently compares new technologies to established technologies. With so many MISTs being developed for LUTS/BPH, the Panel is compelled to consider the necessary attributes to qualify as reasonable MIST therapies, as well as which patient characteristics will likely confer successful outcomes with each individual MIST option. From the patient perspective, the hallmarks of a successful MIST might include: 1. Tolerability, 2. Rapid and significant relief of symptoms, 3. Short recovery time with rapid return to life activities, 4. Low risk of serious complications 5. Preservation of sexual function and continence, and 6. Affordability. From the urologist's perspective, successful attributes might include: 1. Capacity for performance in an ambulatory setting under reduced anesthesia, 2. A fast learning curve, 3. Generalizability, 4. Ease of performance and follow-up care, 5. Low risk, 6. Applicable to a wide variety of patients.

Traditionally, the primary goal of treatment has been to alleviate bothersome LUTS that result from BOO. While a MIST may not alleviate symptoms to the same degree or durability as more invasive surgical options, a more favorable risk profile and reduced anesthetic risk would make such a treatment attractive to many patients and providers. Since many men discontinue medical therapy, yet proportionately few seek surgery, there is a large clinical need for an effective treatment that is less invasive than surgery. With this treatment class, perhaps a significant portion of men with BOO who have stopped medical therapy can be treated prior to impending bladder dysfunction.

**Treatment and Definition of Efficacy and Treatment Failure**

Studies of comparative efficacy of behavioral and lifestyle intervention versus medical treatment; medical therapies versus MISTs; and surgical treatments compared to each other are lacking and would be of great benefit for all levels of providers and patients, and perhaps result in cost savings. Models could include population science, the development of registries, and analysis of electronic medical records and insurance databases. In addition, a better definition of potential long-term complications of medical therapy needs to be delineated in the quest for enhancing both prescriber and patient choice. The ability of providers to use a calculator with patient parameters to obtain a treatment algorithm, or set of appropriate options, could streamline approaches and care.

In addition, MIST and surgical therapies for BPH require a different regulatory process where only patients who remain in follow-up are seen. Many who recover and no longer have symptoms do not return to the urologist or seek care. With medical therapy, patients remain in the care of their providers as therapy is ongoing and prescription renewals are necessary. This variance in patient interaction can lead to different definitions and criteria for treatment failure and in tracking of rates of retreatment.

More data are needed, and a proposed evidence-based classification system for guiding patient care, reimbursement practices, and research outcomes assessment that is applicable across a variety of surgical treatments is of critical importance.

###  TOOLS & RESOURCES 

[![](images/Guidelines/Guideline%20Images/Patient%20Education%20Thumbnails/ProstateHealth-BPH-PG-2020-English_Thumb.jpg)](https://www.urologyhealth.org/educational-resources/benign-prostatic-hyperplasia-\(bph\))**[Benign Prostatic Hyperplasia (BPH) Patient Guide](https://www.urologyhealth.org/educational-resources/benign-prostatic-hyperplasia-\(bph\)) **  
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###  ABBREVIATIONS 

5- Alpha Reductase Inhibitor| 5-ARI  
---|---  
95 Percent Confidence Interval| 95%CI  
Acute Urinary Retention| AUR  
American Urological Association| AUA  
AUA-Symptom Index| AUA-SI  
Benign Prostatic Enlargement| BPE  
Benign Prostatic Hyperplasia| BPH  
Benign Prostatic Obstruction| BPO  
Bladder Outlet Obstruction| BOO  
Clinical Controlled Trials| CCT  
Computed Tomography| CT  
Dihydrotestosterone| DHT  
Ejaculatory Dysfunction| EjD  
Erectile Dysfunction| ED  
Erectile Function| EF  
Global Subjective Assessment| GSA  
Holmium Laser Enucleation of the Prostate| HoLEP  
International Index of Erectile Function| IIEF  
Intraoperative Floppy Iris Syndrome| IFIS  
International Prostate Symptom Score| IPSS  
Laparoscopic Simple Prostatectomy/Enucleation| LSP  
Low Molecular Weight Heparin| LMWH  
Lower Urinary Tract Symptoms| LUTS  
Male Lower Urinary Tract Symptoms Secondary/attributed to BPH| LUTS/BPH  
Magnetic Resonance Imaging| MRI  
Medical Therapy of Prostatic Symptoms| MTOPS  
Minimally Detectable Difference| MDD  
Minimally Invasive Surgical Therapies| MIST  
Open Simple Prostatectomy| OSP  
Overactive Bladder| OAB  
Patient Perception of Study Medication| PPMS  
Phosphodiesterase-5| PDE5  
Photoselective Vaporization of the Prostate| PVP  
Post-Void Residual| PVR  
Prostate Artery Embolization| PAE  
Prostate Specific Antigen| PSA  
Prostatic Urethral Lift| PUL  
Quality of Life| QoL  
Randomized Controlled Trials| RCT  
Retrograde Ejaculation| RE  
Risk of Bias| ROB  
Risk Ratio| RR  
Robotic-Assisted Laparoscopic Simple Prostatectomy| RASP  
Robotic Waterjet Treatment| RWT  
Temporary Implanted Prostatic Devices| TIPD  
Thulium Laser Enucleation of the Prostate| ThuLEP  
Transurethral Incision of the Prostate| TUIP  
Transurethral Needle Ablation| TUNA  
Transurethral Resection of the Prostate| TURP  
Transurethral Ultrasound| TRUS  
Transurethral Vaporization of the Prostate| TUVP  
Trial Without Catheter| TWOC  
Urinary Tract Infection| UTI  
Water Vapor Thermal Therapy| WVTT  
Weighted Mean Difference| WMD  
  
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