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Home Guidelines Guidelines Clinical Guidelines Benign Prostatic Hyperplasia (BPH) Guideline

Management of Benign Prostatic Hyperplasia/ Lower Urinary Tract Symptoms: AUA Guideline 2021

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:

  • Lerner LB, McVary, KT, Barry MJ et al: Management of lower urinary tract symptoms attributed to benign prostatic hyperplasia: AUA Guideline part I, initial work-up and medical management. J Urol 2021; 206: 806.
  • Lerner LB, McVary, KT, Barry MJ et al: Management of lower urinary tract symptoms attributed to benign prostatic hyperplasia: AUA Guideline part II, surgical evaluation and treatment . J Urol 2021; 206: 818.

Guideline summaries as they appear in The Journal of Urology® (2021) Part I, Part II

Unabridged version of this guideline [pdf]
Surgical Mangement Algorithm associated with this guideline [pdf]
Trial of Medical Therapy Algorithm associated with this guideline [pdf]
Basic Management Algorithm associated with this guideline [pdf]

Panel Members

J. Kellogg Parsons, MD; 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; Claus G. Roehrborn, MD; John T. Stoffel, MD; Charles Welliver, MD; Kevin T. McVary, MD

Guideline Statements

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.

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 counselled 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

  1. 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)
  2. 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

  1. 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)
  2. Clinicians should perform a PVR assessment prior to intervention for LUTS/BPH. (Clinical Principle)
  3. Clinicians should consider uroflowmetry prior to intervention for LUTS/BPH. (Clinical Principle)
  4. Clinicians should consider pressure flow studies prior to intervention for LUTS/BPH when diagnostic uncertainty exists. (Expert Opinion)
  5. 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

  1. 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)
  2. 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)

  1. 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)

  1. 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 > 30cc on imaging, a prostate specific antigen (PSA) > 1.5ng/dL, or palpable prostate enlargement on digital rectal exam (DRE). (Moderate Recommendation; Evidence Level: Grade B)
  2. 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)
  3. 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)
  4. 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)

  1. 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

  1. 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 > 30cc on imaging, a PSA >1.5ng/dL, or palpable prostate enlargement on DRE. (Strong Recommendation; Evidence Level: Grade A)
  2. 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)
  3. 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)
  4. Clinicians should not offer the combination of low-dose daily 5mg tadalafil with alpha blockers for the treatment of LUTS/BPH as it offers no advantages in symptom improvement over either agent alone. (Moderate Recommendation; Evidence Level: Grade C)

Acute Urinary Retention (AUR) Outcomes

  1. 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).
  2. 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)
  3. 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

  1. 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)
  2. 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)

  1. TURP should be offered as a treatment option for patients with LUTS/BPH. (Moderate Recommendation; Evidence Level: Grade B)
  2. 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

  1. 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)

  1. TUIP should be offered as an option for patients with prostates ≤30cc for the surgical treatment of LUTS/BPH. (Moderate Recommendation; Evidence Level: Grade B)

Transurethral Vaporization of the Prostate (TUVP)

  1. 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)

  1. 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)

  1. PUL should be considered as a treatment option for patients with LUTS/BPH provided prostate volume 30-80cc and verified absence of an obstructive middle lobe. (Moderate Recommendation; Evidence Level: Grade C)
  2. 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)

Transurethral Microwave Therapy (TUMT)

  1. TUMT may be offered as a treatment option to patients with LUTS/BPH. (Conditional Recommendation; Evidence Level: Grade C)

Water Vapor Thermal Therapy (WVTT)

  1. WVTT should be considered as a treatment option for patients with LUTS/BPH provided prostate volume 30-80cc. (Moderate Recommendation; Evidence Level: Grade C)
  2. 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)

Transurethral Needle Ablation (TUNA)

  1. TUNA is not recommended for the treatment of LUTS/BPH. (Expert Opinion)

Laser Enucleation

  1. 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)

  1. Robotic waterjet treatment (RWT) may be offered as a treatment option to patients with LUTS/BPH provided prostate volume 30-80cc. (Conditional Recommendation; Evidence Level: Grade C)

Prostate Artery Embolization (PAE)

  1. PAE for the routine treatment of LUTS/BPH is not supported by current data, and benefit over risk remains unclear; therefore, PAE is not recommended outside the context of clinical trials. (Expert Opinion)

Hematuria

  1. 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

  1. 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

The American Urological Association (AUA) Guideline: Management of BPH was last revised in 2010.1 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. 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, 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.

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.

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.

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 ROB2 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 5.1.3 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 RevMan4 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 GRADEpro5 based on five assessed domains.6,7 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.

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 1). 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 that there is no apparent net benefit or harm or when the balance between benefits and risks/burdens 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 that 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 that the statement can be applied to most patients in most circumstances but that better evidence could change confidence. Body of evidence strength Grade C in support of a Strong or Moderate Recommendation indicates that the statement can be applied to most patients in most circumstances but that 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 also can be supported by any evidence strength. When body of evidence strength is Grade A in support of a Conditional Recommendation, the statement indicates that 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, the Panel provides guidance in the form of Clinical Principles or Expert Opinions with consensus achieved using a modified Delphi technique if differences of opinion emerged. A Clinical Principle is a statement about a component of clinical care that is 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, achieved by consensus of the Panel, that is based on members' clinical training, experience, knowledge, and judgment for which there may or may not be evidence in the medical literature.

TABLE 1: AUA Nomenclature Linking Statement Type to Level of Certainty, Magnitude of Benefit or Risk/Burden, and Body of Evidence Strength
 Evidence Strength A(High Certainty)Evidence Strength B(Moderate Certainty)Evidence Strength C(Low Certainty)
Strong Recommendation   (Net benefit or harm substantial)Benefits > Risks/Burdens (or vice versa) Net benefit (or net harm) is substantial Applies to most patients in most circumstances and future research is unlikely to change confidenceBenefits > Risks/Burdens (or vice versa) Net benefit (or net harm) is substantial Applies to most patients in most circumstances but better evidence could change confidence  Benefits > Risks/Burdens (or vice versa) Net benefit (or net harm) appears substantial Applies to most patients in most circumstances but better evidence is likely to change confidence (rarely used to support a Strong Recommendation)
Moderate Recommendation   (Net benefit or harm moderate) Benefits > Risks/Burdens (or vice versa) Net benefit (or net harm) is moderate Applies to most patients in most circumstances and future research is unlikely to change confidenceBenefits > Risks/Burdens (or vice versa) Net benefit (or net harm) is moderate Applies to most patients in most circumstances but better evidence could change confidenceBenefits > Risks/Burdens (or vice versa) Net benefit (or net harm) appears moderate Applies to most patients in most circumstances but better evidence is likely to change confidence
Conditional Recommendation   (No apparent net benefit or harm) Benefits = Risks/Burdens Best action depends on individual patient circumstances Future research unlikely to change confidenceBenefits = Risks/Burdens Best action appears to depend on individual patient circumstances Better evidence could change confidenceBalance between Benefits & Risks/Burdens unclear Alternative strategies may be equally reasonable Better evidence likely to change confidence
Clinical PrincipleA statement about a component of clinical care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature
Expert OpinionA statement, achieved by consensus of the Panel, that is 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.”8,9 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 5α-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.

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 80.10 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,11 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.12

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.13 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.13,14 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 200613 and the CAMUS trial published in 2011,14 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 ≥7.15 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.16 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.17 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.18

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).19 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.20 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.21 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.22
  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.23 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).20 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.

Evaluation

Initial Evaluation

Guideline Statement 1

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


Guideline Statement 2

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


Follow-Up Evaluation

Guideline Statement 3

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


Guideline Statement 4

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


Preoperative Testing

Guideline Statement 5

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


Guideline Statement 6

6. Clinicians should perform a PVR assessment prior to intervention for LUTS/BPH. (Clinical Principle)

Discussion


Guideline Statement 7

7. Clinicians should consider uroflowmetry prior to intervention for LUTS/BPH. (Clinical Principle)

Discussion


Guideline Statement 8

8. Clinicians should consider pressure flow studies prior to intervention for LUTS/BPH when diagnostic uncertainty exists. (Expert Opinion)

Discussion


Guideline Statement 9

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


Medical Therapy

Alpha Blockers

Guideline Statement 10

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


Guideline Statement 11

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


Alpha Blockers and Intraoperative Floppy Iris Syndrome (IFIS)

Guideline Statement 12

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


5-Alpha Reductase Inhibitor (5-ARI)

Guideline Statement 13

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 > 30cc on imaging, a prostate specific antigen (PSA) > 1.5ng/dL, or palpable prostate enlargement on digital rectal exam (DRE). (Moderate Recommendation; Evidence Level: Grade B)

Discussion


Guideline Statement 14

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


Guideline Statement 15

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


Guideline Statement 16

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


Phosphodiesterase-5 Inhibitor (PDE5)

Guideline Statement 17

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


Combination Therapy

Guideline Statement 18

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 > 30cc on imaging, a PSA >1.5ng/dL, or palpable prostate enlargement on DRE. (Strong Recommendation; Evidence Level: Grade A)

Discussion


Guideline Statement 19

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


Guideline Statement 20

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


Guideline Statement 21

21. Clinicians should not offer the combination of low-dose daily 5mg tadalafil with alpha blockers for the treatment of LUTS/BPH as it offers no advantages in symptom improvement over either agent alone. (Moderate Recommendation; Evidence Level: Grade C)

Discussion


AUR Outcomes

Guideline Statement 22

22. 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 23

23. 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 24

24. 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


Surgical Therapy

Guideline Statement 25

25. 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


Guideline Statement 26

26. 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


Transurethral Resection of the Prostate (TURP)

Guideline Statement 27

27. TURP should be offered as a treatment option for patients with LUTS/BPH. (Moderate Recommendation; Evidence Level: Grade B)

Discussion


Guideline Statement 28

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

Discussion


Simple Prostatectomy

Guideline Statement 29

29. 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


Transurethral Incision of the Prostate (TUIP)

Guideline Statement 30

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

Discussion


Transurethral Vaporization of the Prostate (TUVP)

Guideline Statement 31

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

Discussion


Photoselective Vaporization of the Prostate (PVP)

Guideline Statement 32

32. 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


Prostatic Urethral Lift (PUL)

Guideline Statement 33

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

Discussion


Guideline Statement 34

34. 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


Transurethral Microwave Therapy (TUMT)

Guideline Statement 35

35. TUMT may be offered as a treatment option to patients with LUTS/BPH. (Conditional Recommendation; Evidence Level: Grade C)

Discussion


Water Vapor Thermal Therapy (WVTT)

Guideline Statement 36

36. WVTT should be considered as a treatment option for patients with LUTS/BPH provided prostate volume 30-80cc. (Moderate Recommendation; Evidence Level: Grade C)

Discussion


Guideline Statement 37

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


Transurethral Needle Ablation (TUNA)

Guideline Statement 38

38. TUNA is not recommended for the treatment of LUTS/BPH. (Expert Opinion)

Discussion


Laser Enucleation

Guideline Statement 39

39. 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


Robotic Waterjet Treatment (RWT)

Guideline Statement 40

40. Robotic waterjet treatment (RWT) may be offered as a treatment option to patients with LUTS/BPH provided prostate volume 30-80cc. (Conditional Recommendation; Evidence Level: Grade C)

Discussion


Prostate Artery Embolization (PAE)

Guideline Statement 41

41. PAE for the routine treatment of LUTS/BPH is not supported by current data, and benefit over risk remains unclear; therefore, PAE is not recommended outside the context of clinical trials. (Expert Opinion)

Discussion


Hematuria

Guideline Statement 42

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


Medically Complicated Patients

Guideline Statement 43

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

Discussion


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.373 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 regards 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. It is the hope of this Panel that further data will be available in the peer reviewed literature on these therapies to allow incorporation into future iterations of this Guideline. 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. Future MISTs should strive to attain outcomes similar to standard technologies, with fewer side effects, as well as ability to perform them in an office setting under local anesthesia.

From the patient perspective, the hallmarks of a successful MIST might include: 1. Tolerability, 2. Rapid and durable relief of symptoms, 3. Short recovery time with rapid return to life activities, 4. Minimal adverse events, and 5. 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 from RCT, 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 and Resources

Related Content: 

References

  1. American Urological Association Guideline: management of benign prostatic hyperplasia (BPH). 2010. Available from
  2. DistillerSR [Computer program]. Ottawa, Canada: Evidence Partners. Available from https://www.evidencepartners.com/products/distillersr-systematic-review-software/.
  3. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
  4. Review Manager (RevMan) [Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
  5. GRADEpro GDT: GRADEpro Guideline Development Tool [Software]. McMaster University, 2015 (developed by Evidence Prime, Inc.). Available from gradepro.org.
  6. Balshem H, Helfand M, Schünemann HJ et al: GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011: 64: 401.
  7. Guyatt G, Oxman AD, Akl EA et al: GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011; 64: 383.
  8. Lee C, Kozlowski J, Grayhack J: Intrinsic and extrinsic factors controlling benign prostatic growth. Prostate 1997; 31: 131.
  9. Auffenberg G, Helfan B, McVary K: Established medical therapy for benign prostatic hyperplasia. Urol Clin North Am 2009; 36: 443.
  10. Berry SJ, Coffey DS, Walsh PC et al: The development of human benign prostatic hyperplasia with age. J Urol 1984; 132: 474.
  11. Gades NM, Jacobson DJ, McGree ME et al: Dropout in a longitudinal, cohort study of urologic disease in community men. BMC Med Res Methodol 2006; 6:58.
  12. Reynard J: Does anticholinergic medication have a role for men with lower urinary tract symptoms/benign prostatic hyperplasia either alone or in combination with other agents? Curr Opin Urol 2004; 14: 13.
  13. Bent S, Kane C, Shinohara K et al: Saw palmetto for benign prostatic hyperplasia. N Engl J Med 2006; 354: 557.
  14. Barry MJ, Meleth S, Lee JY et al; Complementary and alternative medicine for urological symptoms (CAMUS) study group. Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial. JAMA 2011; 306: 1344.
  15. Welliver C, Feinstein L, Ward JB et al: Trends in lower urinary tract symptoms associated with benign prostatic hyperplasia, 2004 to 2013: the Urologic Diseases in America Project. J Urol 2020; 203: 171.
  16. McVary K: BPH: Epidemiology and Comorbidities. Am J Manag Care 12 2006; 5 Suppl: S122.
  17. Wei J, Calhoun E, Jacobsen S: Urologic diseases in America project: benign prostatic hyperplasia. J Urol 2005; 173: 1256.
  18. O'Leary M: LUTS, ED, QOL: alphabet soup or real concerns to aging men? Urology 2000; 56: 7.
  19. Barry MJ, Fowler FJ, Jr., O'Leary MP et al: The american urological association symptom index for benign prostatic hyperplasia. The measurement committee of the american urological association. J Urol 1992; 148: 1549.
  20. McConnell J, Roehrborn C, Bautista O et al: The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003; 349: 2387.
  21. Nguyen DD, Marchese M, Cone EB et al: Investigation of suicidality and psychological adverse events in patients treated with finasteride. JAMA Dermatol 2021; 157: 35.
  22. Sajadi KP, Terris MK, Hamilton RJ et al: Body mass index, prostate weight and transrectal ultrasound prostate volume accuracy. J Urol 2007; 178: 990.
  23. Fwu CW, Eggers PW, Kirkali Z et al: Change in sexual function in men with lower urinary tract symptoms/benign prostatic hyperplasia associated with long-term treatment with doxazosin, finasteride and combined therapy. J Urol 2014; 191: 1828.
  24. Reynard JM, Yang Q, Donovan JL et al: The ICS-'BPH' Study: uroflowmetry, lower urinary tract symptoms and bladder outlet obstruction. Br J Urol 1998; 82: 619.
  25. Brown CT, Yap T, Cromwel DA et al: Self management for men with lower urinary tract symptoms: randomised controlled trial. Bmj, 334: 25, 2007.
  26. Burgio KL, Kraus SR, Johnson TM 2nd, et al: Effectiveness of combined behavioral and drug therapy for overactive bladder symptoms in men: A randomized clinical trial. JAMA Intern Med 2020; 180:411.
  27. Barry MJ, Williford WO, Chang Y et al: Benign prostatic hyperplasia specific health status measures in clinical research: how much change in the American Urological Association symptom index and the benign prostatic hyperplasia impact index is perceptible to patients? J Urol 1995; 154:1770.
  28. Roehrborn CG, Wilson TH, Black LK: Quantifying the contribution of symptom Improvement to satisfaction of men with moderate to severe benign prostatic hyperplasia: 4-year data from the CombAT trial. J Urol 2014; 187: 1732.
  29. Rieken M, Presicce F, Autorino R et al: Clinical significance of intravesical prostatic protrusion in the management of benign prostatic enlargement: a systematic review and critical analysis of current evidence. Minerva Urol Nefrol 2017; 69: 548.
  30. Verma M, Morgan JM: The weight of the prostate gland is an excellent surrogate for gland volume. Histopathology 2010; 57: 55.
  31. Stone BV, Shoag J, Halpern JA et al: Prostate size, nocturia and the digital rectal examination: a cohort study of 30 500 men.. BJU Int 2017; 119: 298.
  32. Rhodes T, Girman CJ, Jaconsen SJ et al: Longitudinal prostate growth rates during 5 years in randomly selected community men 40–79 years old. J Urol 1999; 161: 1174.
  33. Lu SH, Chen CS: Natural history and epidemiology of benign prostatic hyperplasia. Formosan Journal of Surgery 2014; 47: 207.
  34. Kim SB, Cho IC, Min SK: Prostate volume measurement by transrectal ultrasonography: comparison of height obtained by use of transaxial and midsagittal scanning. Korean J Urol 2014; 55: 470.
  35. Asimakopoulos AD, De Nunzio C, Kocjancic E et al: Measurement of post-void residual urine. Neurourol Urodyn 2016; 35: 55.
  36. Abrams P: Objective evaluation of bladder outlet obstruction. Br J Urol 1995; 76: 11.
  37. Nitti VW: Pressure flow urodynamic studies: the gold standard for diagnosing bladder outlet obstruction. Rev Urol 2005; 7: S14.
  38. Lewis AL, Young GL, Selman LE, et al: Urodynamics tests for the diagnosis and management of bladder outlet obstruction in men: the UPSTREAM non-inferiority RCT. Health Technol Assess 2020; 24: 1.
  39. Rademakers KL, van Koeveringe GA, Oelke M: Detrusor underactivity in men with lower urinary tract symptoms/benign prostatic obstruction: characterization and potential impact on indications for surgical treatment of the prostate. Curr Opin Urol 2016; 26: 3.
  40. McVary KT and Kaplan SA: A tower of babel in today's urology: Disagreement in concepts and definitions of lower urinary tract symptoms/benign prostatic hyperplasia re-treatment. J Urol 2020; 204: 213.
  41. Taylor BL, Jaffe WI: Electrosurgical transurethral resection of the prostate and transurethral incision of the prostate (monopolar techniques). Can J Urol 2015; 22: 24.
  42. Lourenco T, Shaw M, Fraser C et al: The clinical effectiveness of transurethral incision of the prostate: a systematic review of randomised controlled trials. World J Urol 2010; 28: 23.
  43. Abd-El Kader O, Mohy El Den K, El Nashar A et al: Transurethral incision versus transurethral resection of the prostate in small prostatic adenoma: long-term follow-up. Afr J Urol 2012; 18: 29.
  44. Yip SK, Chan NH, Chiu P et al: A randomized controlled trial comparing the efficacy of hybrid bipolar transurethral vaporization and resection of the prostate with bipolar transurethral resection of the prostate. J Endourol 2011; 25: 1889.
  45. Gupta N, Sivaramakrishna, Kumar R et al: Comparison of standard transurethral resection, transurethral vapour resection and holmium laser enucleation of the prostate for managing benign prostatic hyperplasia of >40 g. BJU Int. 2006; 97: 85.
  46. Gupta NP, Doddamani D, Aron M et al: Vapor resection: a good alternative to standard loop resection in the management of prostates >40 cc. J Endourol 2002; 16: 767.
  47. Helke C, Manseck A, Hakenberg OW et al: Is transurethral vaporesection of the prostate better than standard transurethral resection? Eur Urol 2001; 39: 551.
  48. Kupeli S, Yilmaz E, Soygur T et al: Randomized study of transurethral resection of the prostate and combined transurethral resection and vaporization of the prostate as a therapeutic alternative in men with benign prostatic hyperplasia. J Endourol 2001; 15: 317.
  49. Perk H, Serel TA, Kosar A et al: Comparative early results of the sandwich technique and transurethral electroresection in benign prostatic hyperplasia. Prostate Cancer Prostatic Dis 2001; 4: 242.
  50. Bachmann A, Tubaro A, Barber N et al: 180-W XPS GreenLight laser vaporisation versus transurethral resection of the prostate for the treatment of benign prostatic obstruction: 6-month safety and efficacy results of a European Multicentre Randomised Trial--the GOLIATH study. Eur Urol 2014; 65: 931.
  51. Thomas JA, Tubaro A, Barber N et al: A multicenter randomized noninferiority trial comparing GreenLight-XPS laser vaporization of the prostate and transurethral resection of the prostate for the treatment of benign prostatic obstruction: two-yr outcomes of the GOLIATH Study. Eur Urol 2016; 69: 94.
  52. Elhilali MM and Elkoushy MA: Greenlight laser vaporization versus transurethral resection of the prostate for treatment of benign prostatic obstruction: evidence from randomized controlled studies. Transl Androl Urol 2016; 5: 388.
  53. Hueber PA, Ben-Zvi T, Liberman D et al: Mid term outcomes of initial 250 case experience with GreenLight 120W-HPS Photoselective vaporization prostatectomy for benign prostatic hyperplasia: comparison of prostate volumes <60 cc, 60 cc-100 cc and > 100cc. Can J Urol 2012; 19: 6450.
  54. Elshal AM, Soltan M, El-Tabey NA et al: Randomised trial of bipolar resection vs holmium laser enucleation vs greenlight laser vapo-enucleation of the prostate for treatment of large benign prostate obstruction: 3-years outcomes. BJU Int 2020; 126: 731.
  55. Barkin J, Gange SN, et al: Five year results of the prospective randomized controlled prostatic urethral L.I.F.T. study. Canadian Journal of Urology 2017; 24: 8802.
  56. Gratzke C, Barber N, Speakman M, et al: Prostatic urethral lift vs transurethral resection of the prostate: 2-year results of the BPH6 prospective, multicentre, randomized study. BJU Int 2017; 119: 767.
  57. Albala DM, Fulmer BR, Turk TT et al: Office-based transurethral microwave thermotherapy using the TherMatrx TMx-2000. J Endourol 2002; 16: 57.
  58. Brehmer M, Wiskell H, Kinn AC: Sham treatment compared with 30 or 60 min of thermotherapy for benign prostatic hyperplasia: a randomized study. BJU Int 1999; 84: 292.
  59. De la Rosette JJ, Floratos DL, Severens JL et al: Transurethral resection vs microwave thermotherapy of the prostate: a cost-consequences analysis. BJU Int 2003; 92: 713.
  60. Floratos DL, Lambertus LA, Rossi C et al: Long-term followup of randomized transurethral microwave thermotherapy versus transurethral prostatic resection study. J Urol 2001; 165: 1533.
  61. Norby B, Nielsen HV, Frimodt-Moller PC et al: Transurethral interstitial laser coagulation of the prostate and transurethral microwave thermotherapy vs transurethral resection or incision of the prostate: results of a randomized controlled study in patients with symptomatic benign prostatic hyperplasia. BJU Int 2002; 90: 853.
  62. Schelin S, Geertsen U, Walter S et al: Feedback microwave thermotherapy versus TURP/prostate enucleation surgery in patients with benign prostatic hyperplasia and persistent urinary retention: a prospective, randomized, controlled, multicenter study. Urology 2006, 68: 795.
  63. Wagrell L, Schelin S, Nordlinf J et al: Feedback microwave thermotherapy versus TURP for clinical BPH-a randomized controlled multicenter study. Urology 2002; 60; 292.
  64. Wagrell L, Schelin S, Nordlinf J et al: Three-year follow-up of feedback microwave thermotherapy versus TURP for clinical BPH: A prospective randomized multicenter study. Urology 2004; 64: 698.
  65. Mattiasson A, Wagrell L, Schelin S et al: Five-year follow-up of feedback microwave thermotherapy versus TURP for clinical BPH: a prospective randomized multicenter study. Urology 2007; 69: 91.
  66. Zhang B, Wu G, Chen C et a:. Combination of channel-TURP and ILC versus standard TURP or ILC for elderly with benign prostatic hyperplasia: a randomized prospective trial. Urol Int 2011; 87: 392.
  67. McVary KT, Gange SN, Gittelman MC et al: Minimally invasive prostate convective water vapor energy ablation: a multicenter, randomized, controlled study for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2016; 195: 1529.
  68. McVary KT, Gange SN, Gittelman MC et al: Erectile and ejaculatory function preserved with convective water vapor energy treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: randomized controlled study. J Sex Med 2016; 13: 924.
  69. Roehrborn C, Gange SN, Gittleman MC et al: Convective thermal therapy: durable 2-year results of randomized controlled and prospective crossover studies for treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. J Urol 2017; 197: 1507.
  70. McVary KT, Roehrborn CG: Three-year outcomes of the prospective, randomized controlled Rezum System study: convective radiofrequency thermal therapy for treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. Urology 2018;111:1.
  71. McVary KT, Rogers T, Roehrborn CG. Rezum water vapor thermal therapy from lower urinary tract symptoms associated with benign prostatic hyperplasia: 4-year results from randomized controlled study. Urology 2019; 126: 171.
  72. Hamouda A, Morsi G, Habib E et al: A comparative study between holmium laser enucleation of the prostate and transurethral resection of the prostate: 12-month follow-up. Journal of Clinical Urology 2014; 7: 99.
  73. Ahyai S, Lehrich K, Kuntz R: Holmium laser enucleation versus transurethral resection of the prostate: 3-year follow-up results of a randomized clinical trial. Eur Urol 2007; 52: 1456.
  74. Gilling PJ, Wilson LC, King CJ et al: Long-term results of a randomized trial comparing holmium laser enucleation of the prostate and transurethral resection of the prostate: results at 7 years. BJU Int 2012; 109: 408.
  75. Cui D, Sun F, Zhuo J et al: A randomized trial comparing thulium laser resection to standard transurethral resection of the prostate for symptomatic benign prostatic hyperplasia: four-year follow-up results. World J Urol 2014; 32: 683.
  76. Yan H, Ou TW, Chen L et al: Thulium laser vaporesection versus standard transurethral resection of the prostate: a randomized trial with transpulmonary thermodilution hemodynamic monitoring. Int J Urol 2013; 20: 507.
  77. Świniarski PP, Stępień S, Dudzic W et al: Thulium laser enucleation of the prostate (TmLEP) vs. transurethral resection of the prostate (TURP): evaluation of early results. Cent European J Urol 2012; 63: 130.
  78. Zhang J, Wang X, Zhang Y, et al: 1470 nm diode laser enucleation vs plasmakinetic resection of the prostate for benign prostatic hyperplasia: a randomized study. J Endourol 2019; 33: 211.
  79. Gilling PJ, Barber N, Bidair M et al: Randomized controlled trial of aquablation versus transurethral resection of the prostate in benign prostatic hyperplasia: One-year outcomes. Urology 2019; 125: 169.
  80. Gilling P, Barber N, Bidair M et al: Three-year outcomes after aquablation therapy compared to turp: Results from a blinded randomized trial. Can J Urol 2020; 27: 10072.
  81. Yuan JQ, Mao C, Wong SY et al: Comparative effectiveness and safety of monodrug therapies for lower urinary tract symptoms associated with benign prostatic hyperplasia: a network meta-analysis version 2. Medicine (Baltimore) 2015; 94: 974.
  82. Djavan B, Marberger M: A meta-analysis on the efficacy and tolerability of alpha1-adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction. Eur Urol 1999; 36:1.
  83. Dahm P, Brasure M, MacDonald et al: Comparative effectiveness of newer medications for lower urinary tract symptoms attributed to benign prostatic hyperplasia: a systematic review and meta-analysis. Eur Urol 2017; 71: 570.
  84. Lee M: Tamsulosin for the treatment of benign prostatic hypertrophy. Ann Pharmacother 2000; 34: 188.
  85. Roehrborn CG, Van Kerrebroeck P, Nordling J et al: Safety and efficacy of alfuzosin 10 mg once-daily in the treatment of lower urinary tract symptoms and clinical benign prostatic hyperplasia: a pooled analysis of three double-blind, placebo-controlled studies. BJU Int 2003; 92: 257.
  86. Marks LS, Gittelman MC, Hill LA, et al: Rapid efficacy of the highly selective alpha1A-adrenoceptor antagonist silodosin in men with signs and symptoms of benign prostatic hyperplasia: pooled results of 2 phase 3 studies. J Urol 2009; 181: 2634.
  87. Schwinn DA, Price DT, Narayan P et al: Alpha1-Adrenoceptor subtype selectivity and lower urinary tract symptoms. Mayo Clin Proc 2004; 79: 1423.
  88. Nieminen T, Tammela TL, Kööbi T et al: The effects of tamsulosin and sildenafil in separate and combined regimens on detailed hemodynamics in patients with benign prostatic enlargement. J Urol 2006; 176: 2551.
  89. Gacci M, Ficarra V, Sebastianelli A et al: Impact of medical treatments for male lower urinary tract symptoms due to benign prostatic hyperplasia on ejaculatory function: a systematic review and meta-analysis. J Sex Med 2014; 11: 1554.
  90. Hellstrom WJ, Sikka SC: Effects of acute treatment with tamsulosin versus alfuzosin on ejaculatory function in normal volunteers. J Urol 2006; 176: 1529.
  91. Creta M, Cornu JN, Roehrborn C et al: Clinical efficacy of silodosin in patients with severe lower urinary tract symptoms related to benign prostatic obstruction: a pooled analysis of phase 3 and 4 trials. Eur Urol Focus 2020; 20: S2405.
  92. Roehrborn CG, Kaplan SA, Lepor H et al: Symptomatic and urodynamic responses in patients with reduced or no seminal emission during silodosin treatment for LUTS and BPH. Prostate Cancer Prostatic Dis 2011; 14: 143.
  93. Chang D, Campbell J: Intraoperative floppy iris syndrome associated with tamsulosin. J Cataract Refract Surg 2005; 31: 664.
  94. Abdel-Aziz S, Mamalis N: Intraoperative floppy iris syndrome. Curr Opin Ophthalmol 2009; 20: 37.
  95. Chatziralli, IP, et al: Risk factors for intraoperative floppy iris syndrome: a meta-analysis. Ophthalmology 2011. 118: 730.
  96. Bell C, Hatch W, Fischer H et al: Association between tamsulosin and serious ophthalmic adverse events in older men following cataract surgery. JAMA 2009; 116: 425.
  97. Lunacek A, Mohamad Al-Ali B, Radmayr C, et al: Ten years of intraoperative floppy iris syndrome in the era of α-blockers. Cent Eur J Urol 2018; 71: 98.
  98. Campbell RJ, El-Defrawy SR, Gill SS et al: Evolution in the risk of cataract surgical complications among patients exposed to tamsulosin: a population-based study. Ophthalmology 2019; 126: 490.
  99. Christou CD, Tsinopoulos, Ziakas N et al: Intraoperative floppy iris syndrome: updated perspectives. Clin Ophthalmol 2020; 14: 463.
  100. Chang DF, Osher RH, Wang L, Koch DD. Prospective muticenter evaluation of cataract surgery in patients taking tamsulosin. Ophthalmology 2007; 114: 957.
  101. Nguyen DQ, Sebastian RT, Kyle G: Surgeon’s experiences of the intraoperative floppy iris syndrome in the United Kingdom. Eye (Lond) 2007; 21: 443.
  102. Andriole G, Bruchovsky N, Chung L et al: Dihydrotestosterone and the prostate: the scientific rationale for 5alpha-reductase inhibitors in the treatment of benign prostatic hyperplasia. J Urol 2004; 172: 1399.
  103. Russell D, Wilson J: Steroid 5alpha-reductase: two genes/two enzymes. Annu Rev Biochem 1994; 63: 25.
  104. Bruskewitz R, Girman C, Fowler J et al: Effect of finasteride on bother and other health-related quality of life aspects associated with benign prostatic hyperplasia. PLESS Study Group. Proscar Long-term Efficacy and Safety Study. Urology 1999; 54: 670
  105. Kaplan S: 5alpha-reductase inhibitors: what role should they play? Urology 2001; 58: 65
  106. Kaplan SA, Chung DE, Lee RK et al: A 5-year retrospective analysis of 5α-reductase inhibitors in men with benign prostatic hyperplasia: finasteride has comparable urinary symptom efficacy and prostate volume reduction, but less sexual side effects and breast complications than dutasteride. Int J Clin Pract 2012; 66: 1052.
  107. Cohen S, Werrmann J: Comparison of the effects of new specific azasteroid inhibitors of steroid 5 alpha-reductase on canine hyperplastic prostate: suppression of prostatic DHT correlated with prostate regression. Prostate 1995; 26: 55.
  108. Clark R, Hermann D, Cunningham G et al: Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. J Clin Endocrinol Metab 2004; 89: 2179.
  109. Ju X, Wu H, Zhang W et al: The clinical efficacy of epristeride in the treatment of benign prostatic hyperplasia. Zhonghua Nan Ke Xue 2002; 8: 42.
  110. McConnell J, Wilson J, Goerge F et al: Finasteride, and inhibitor of 5α-Reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia. J Clin Endocrinol Metab 1992; 74: 505.
  111. Wurzel R, Ray P, Major-Walker K et al: The effect of dutasteride on intraprostatic dihydrotestosterone concentrations in men with benign prostatic hyperplasia. Prostate Cancer Prostatic Dis 2007; 10: 149.
  112. Bramson H, Hermann D, Batchelor K et al: Unique preclinical characteristics of GG745, a potent dual inhibitor of 5AR. J Pharmacol Exp Ther 1997; 282: 1496.
  113. Vaughan D, Imperato-McGinley J, McConnell J et al: Long-term (7 to 8-year) experience with finasteride in men with benign prostatic hyperplasia. Urology 2002; 60: 1040.
  114. Lam J, Romas N, Lowe F: Long-term treatment with finasteride in men with symptomatic benign prostatic hyperplasia: 10-year follow-up. Urology 2003; 61: 354.
  115. Roehrborn CG, Boyle P, Gould AL et al: Serum prostate-specific antigen as a predictor of prostate volume in men with benign prostatic hyperplasia. Urology 1999; 53: 581.
  116. Roehrborn CG, Boyle P, Bergner D et al: Serum prostate-specific antigen and prostate volume predict long-term changes in symptoms and flow rate: results of a four-year, randomized trial comparing finasteride versus placebo. PLESS Study Group. Urology 1999; 54: 662.
  117. Boyle P, Roehrborn C, Gould L: Baseline serum PSA levels predict degree of symptom improvement following therapy of BPH with finasteride. Journal of Urology 1997; 157: 134A.
  118. Roehrborn CG, McConnell JD, Lieber M et al: Serum prostate-specific antigen concentration is a powerful predictor of acute urinary retention and need for surgery in men with clinical benign prostatic hyperplasia. PLESS Study Group. Urology 1999; 53: 473.
  119. Administration USFaD: 5-alpha reductase inhibitor information. 2016. https://www.fda.gov/drugs/information-drug-class/5-alpha-reductase-inhibitor-information. 01/28/2021.
  120. Roehrborn CG, Boyle P, Nickel JC et al: Efficacy and safety of a dual inhibitor of 5-alphareductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 2002; 60: 434.
  121. Roehrborn CG, Lukkarinen O, Mark S et al: Long-term sustained improvement in symptoms of benign prostatic hyperplasia with the dual 5alpha-reductase inhibitor dutasteride: results of 4- year studies. BJU Int 2005; 96: 572.
  122. Roehrborn CG, Siami P, Barkin J et al: The effects of dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the CombAT study. J Urol 2008; 179: 616.
  123. Roehrborn CG, Boyle, P., Nickel, J. C., Hoefner, K., Andriole, G.: Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 2002; 60: 434.
  124. Toren P, Margel D, Kulkarni G, et al: Effect of dutasteride on clinical progression of benign prostatic hyperplasia in asymptomatic men with enlarged prostate: a post hoc analysis of the REDUCE study. BMJ 2013; 346: 1.
  125. Nickel JC, Gilling P, Tammela TL: Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS). BJU Int. 2011; 108: 388.
  126. Thompson IM, Goodman PJ, Tangen CM et al: The influence of finasteride on the development of prostate cancer. N Engl J Med 2003; 349: 215.
  127. Roehrborn CG, Andriole GL, Wilson TH et al: Effect of dutasteride on prostate biopsy rates and the diagnosis of prostate cancer in men with lower urinary tract symptoms and enlarged prostates in the combination of avodart and tamsulosin trial. Eur Urol 2011; 59: 244.
  128. Sarkar RR, Parsons JK, Bryant AK et al: Association of treatment with 5α-reductase inhibitors with time to diagnosis and mortality in prostate cancer. JAMA Intern Med 2019; 179: 812.
  129. McConnell JD, Bruskewitz R, Walsh P et al: The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group. N Engl J Med 1998; 338: 557.
  130. Boyle P, Gould AL, Roehrborn CG: Prostate volume predicts outcome of treatment of benign prostatic hyperplasia with finasteride: meta-analysis of randomized clinical trials. Urology 1996; 48: 398.
  131. Andriole GL, Bostwick DG, Brawley OW et al: Effect of dutasteride on the risk of prostate cancer. N Engl J Med 2010; 362: 1192.
  132. Grubb RL, Andriole GL, Somerville MC et al: The REDUCE follow-up study: low rate of new prostate cancer diagnoses observed during a 2-Year, observational, followup study of men who participated in the REDUCE trial. J Urology 2013; 189: 871.
  133. Haque N, Masumori N, Sakamoto S, et al. Superiority of dutasteride 0.5 mg and tamsulosin 0.2 mg for the treatment of moderate-to-severe benign prostatic hyperplasia in Asian men. Int J Urol. 2018;25:944-951.
  134. Roehrborn CG, Perez I, Roos E, et al. Efficacy and safety of a fixed-dose combination of dutasteride and tamsulosin treatment (Duodart®) compared with watchful waiting with initiation of tamsulosin therapy if symptoms do not improve, both provided with lifestyle advice, in the management of treatment-naïve men with moderately symptomatic benign prostatic hyperplasia: 2-year CONDUCT study results. BJU Int. 2015;116:450-459.
  135. Fwu CW, Eggers PW, Kirkali Z et al: Change in sexual function in men with lower urinary tract symptoms/benign prostatic hyperplasia associated with long-term treatment with doxazosin, finasteride and combined therapy. 2014; 191: 1828.
  136. Wessells H, Roy, J., Bannow, J., Grayhack, J., Matsumoto, A. M., Tenover, L., Herlihy, R., Fitch, W., Labasky, R., Auerbach, S., Parra, R., Rajfer, J., Culbertson, J., Lee, M., Bach, M.A., Waldstreicher, J.: Incidence and severity of sexual adverse experiences in finasteride and placebo-treated men with benign prostatic hyperplasia. Urology 2003; 61: 579.
  137. Roehrborn CG, Manyak MJ, Palacios-Moreno JM et al: A prospective randomised placebo-controlled study of the impact of dutasteride/tamsulosin combination therapy on sexual function domains in sexually active men with lower urinary tract symptoms (luts) secondary to benign prostatic hyperplasia (bph). BJU Int 2018; 121: 647.
  138. Hagberg K, Divan HA, Fang SC et al: Risk of gynecomastia and breast cancer associated with the use of 5-alpha reductase inhibitors for benign prostatic hyperplasia. Clin Epidemiology 2017; 9: 83.
  139. Fang Q, Chen P, Du N et al: Analysis of data from breast diseases treated with 5-alpha reductase inhibitors for benign prostatic hyperplasia. Clin Breast Cancer 2019; 19: e624.
  140. Duan Y, Grady JJ, Albertsen PC et a:. Tamsulosin and the risk of dementia in older men with benign prostatic hyperplasia. Pharmacoepidemiol Drug Saf 2018; 27: 340.
  141. Welk B, McArthur E, Ordon M et al: The risk of dementia with the use of 5 alpha reductase inhibitors. J Neurol Sci. 2017; 379: 109.
  142. Welk B, McArthur E, Ordon M et al: Association of Suicidality and Depression With 5α-Reductase Inhibitors. JAMA Intern Med 2017; 177: 683.
  143. Hagberg K, Divan HA, Nickel JC et al: Risk of Incident Antidepressant-Treated Depression Associated with Use of 5a-Reductase Inhibitors Compared with Use of a-Blockers in Men with Benign Prostatic Hyperplasia: A Population-Based Study Using the Clinical Practice Research Datalink. Pharmacotherapy 2017; 37: 517.
  144. Nguyen DD, Marchese M, Cone EB et al: Investigation of suicidality and psychological adverse events in patients treated with finasteride. JAMA Dermatol 2021; 157: 35.
  145. Wei L, Lai E, Kao-ang Y et al: Incidence of type 2 diabetes mellitus in men receiving steroid 5α-reductase inhibitors: population based cohort study. BMJ 2019; 365.
  146. Lee S, Yang Y, Tsai T et al: 5-alpha-reductase inhibitors and the risk of diabetes mellitus: a nationwide population-based study. The Prostate 2016; 76: 41.
  147. Irwig MS: Persistent sexual side effects of finasteride: Could they be permanent? J Sex Med 2012; 9: 2927.
  148. Irwig MS: Depressive symptoms and suicidal thoughts among former users of finasteride with persistent sexual side effects. J Clin Psychiatry 2012; 73: 1220.
  149. Irwig MS and Kolukula S: Persistent sexual side effects of finasteride for male pattern hair loss. J Sex Med 2011; 8: 1747.
  150. Chiriacò G, Cauci S, Mazzon G et al: An observational retrospective evaluation of 79 young men with long-term adverse effects after use of finasteride against androgenetic alopecia. Andrology 2016; 4: 245.
  151. Bass WR, Butcher MJ, Lwin A et al: A review of the FAERS data on 5-alpha reductase inhibitors: implications for postfinasteride syndrome. Urology 2018; 120: 143.
  152. Harrell MB, Ho K, Te AE et al: An evaluation of the federal adverse events reporting system data on adverse effects of 5-alpha reductase inhibitors. World J Urol 2020;
  153. Mondaini N, Gontero P, Giubilei G et al: Finasteride 5 mg and sexual side effects: how many of these are related to a nocebo phenomenon? J Sex Me. 2007; 4: 1708.
  154. Salonia A, Gallina A, Briganti A et al: Remembered international index of erectile function domain scores are not accurate in assessing preoperative potency in candidates for bilateral nerve-sparing radical retropubic prostatectomy. J Sex Med 2008; 5: 677.
  155. Helfand BT, Fought A, Manvar A, McVary KT: Determining the utility of recalled lower urinary tract symptoms. Urology 2010; 76: 447.
  156. Hill AB: The environment and disease: Association or causation? Proc R Soc Med 1965; 58: 295.
  157. Fwu CW KZ, McVary KT, Burrows PK et al: Cross-sectional and longitudinal associations of sexual function with lower urinary tract symptoms in men with benign prostatic hyperplasia. J Urol 2015; 193: 231.
  158. Unger JM TC, Thompson IM Jr, Tangen CM et al: Long-term consequences of finasteride vs placebo in the prostate cancer prevention trial. J Natl Cancer Inst 2016; 108: 1.
  159. Hagberg KW, Divan HA, Persson R et al: Risk of erectile dysfunction associated with use of 5-α reductase inhibitors for benign prostatic hyperplasia or alopecia: population based studies using the Clinical Practice Research Datalink. BMJ 2016; 354: i4823.
  160. Boccon-Gibod L, Valton M, Ibrahim H et al: [Effect of dutasteride on reduction of intraoperative bleeding related to transurethral resection of the prostate]. Prog Urol 2005; 15: 1085.
  161. Hahn RG, Fagerstrom T, Tammela TL et al: Blood loss and postoperative complications associated with transurethral resection of the prostate after pretreatment with dutasteride. BJU Int 2007; 99: 587.
  162. Donohue JF, Sharma H, Abraham R et al: Transurethral prostate resection and bleeding: a randomized, placebo controlled trial of role of finasteride for decreasing operative blood loss. J Urol 2002; 168: 2024.
  163. Sandfeldt L, Bailey DM, Hahn RG: Blood loss during transurethral resection of the prostate after 3 months of treatment with finasteride. Urology 2001; 58: 972.
  164. Crea G, Sanfilippo G, Anastasi G et al: Pre-surgical finasteride therapy in patients treated endoscopically for benign prostatic hyperplasia. Urol Int 2005; 74: 51.
  165. Ozdal O, Ozden C, Benli K et al: Effect of short-term finasteride therapy on peroperative bleeding in patients who were candidates for transurethral resection of the prostate (TUR-P): a randomized controlled study. Prostate Cancer Prostatic Dis 2005; 8: 215.
  166. Lund L, Moller Ernst-Jensen K, torring N et al: Impact of finasteride treatment on perioperative bleeding before transurethral resection of the prostate: a prospective randomized study. Scand J Urol Nephrol 2005; 39: 160.
  167. Hahn RG, Fagerstrom, T., Tammela, T. L., Van Vierssen Trip, O., Beisland, H. O., Duggan, A. and Morrill, B.: Blood loss and postoperative complications associated with transurethral resection of the prostate after pretreatment with dutasteride. BJU Int 2007; 99: 587.
  168. Sairam K, Kulinskaya E, McNicholas TA et al: Sildenafil influences lower urinary tract symptoms. BJU Int 2002; 90: 836.
  169. Mulhall JP, Guhring P, Parker M et al: Assessment of the impact of sildenafil citrate on lower urinary tract symptoms in men with erectile dysfunction. J Sex Med 2006; 3: 662.
  170. McVary KT, Roehrborn CG, Kaminetsky JC et al: Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2007; 177: 1401.
  171. Egerdie RB, Auerbach S, Roehrborn CG et al: Tadalafil 2.5 or 5 mg Administered Once Daily for 12 Weeks in Men with Both Erectile Dysfunction and Signs and Symptoms of Benign Prostatic Hyperplasia: Results of a Randomized, Placebo-Controlled, Double-Blind Study. JSM 2012; 9: 271.
  172. Kim SC, Park JK, Kim SW et al: Tadalafil Administered Once Daily for Treatment of Lower Urinary Tract Symptoms in Korean men with Benign Prostatic Hyperplasia: Results from a Placebo-Controlled Pilot Study Using Tamsulosin as an Active Control. LUTS 2011; 3: 86.
  173. Oelke M, Giuliano F, Mirone V et al: Monotherapy with Tadalafil or Tamsulosin Similarly Improved Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia in an International, Randomised, Parallel, Placebo-Controlled Clinical Trial. Euro Urol 2012; 61: 917.
  174. Porst H, Kim ED, Casabe AR, et al: Efficacy and safety of tadalafil once daily in the treatment of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: results of an international randomized, double-blind, placebo-controlled trial. Euro Urol 2011; 60: 1105.
  175. Roehrborn CG, McVary KT, Elion-Mboussa A et al: Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a dose finding study. JU 2008; 180: 1228.
  176. Takeda M, Nishizawa O, Imaoka T et al: Tadalafil for the treatment of lower urinary tract symptoms in japanese men with benign prostatic hyperplasia: results from a 12-week placebo-controlled dose-finding study with a 42-week open-label extension. LUTS 2012; 4: 110.
  177. Takeda M, Yokoyama O, Lee S et al: Tadalafil 5 mg once-daily therapy for men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: results from a randomized, double-blind, placebo-controlled trial carried out in Japan and Korea. Int J Urol 2014 ;21: 670.
  178. Yokoyama O, Yoshida M, Kim SC et al: Tadalafil once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia: A randomized placebo- and tamsulosin-controlled 12-week study in Asian men. Int J Urol 2013; 20: 193.
  179. Zhang Z, Li H, Zhang X et al: Efficacy and safety of tadalafil 5 mg once-daily in Asian men with both lower urinary tract symptoms associated with benign prostatic hyperplasia and erectile dysfunction: A phase 3, randomized, double-blind, parallel, placebo- and tamsulosin-controlled study. Int J Urol 2019;26:192.
  180. Dmochowski R, Roehrborn C, Klise S et al: Urodynamic effects of once daily tadalafil in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia: a randomized, placebo controlled 12-week clinical trial.J Urol 2013; 189: S135.
  181. McVary KT, Monning W, Camps JL et al: Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized, double-blind trial. JU 2007; 177: 1071.
  182. Burnett AL, Nehra A, Breau RH et al: Erectile dysfunction: AUA guideline. J Urol 2018; 200: 633.
  183. Lepor H, Williford WO, Barry MJ et al: The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. N Engl J Med 1996; 335: 533.
  184. Kirby RS, Roehrborn C, Boyle P et al: Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial. Urology 2003; 61: 119.
  185. Bautista OM, Kusek JW, Nyberg LM et al: Study design of the Medical Therapy of Prostatic Symptoms (MTOPS) trial. Control Clin Trials 2003; 24: 224.
  186. Lightner DJ, Gomelsky A, Souter L et al: Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU Guideline amendment 2019. J Urol 2019; 202: 558.
  187. Van Kerrebroeck P, Haab F, Angulo JC et al: Efficacy and safety of solifenacin plus tamsulosin ocas in men with voiding and storage lower urinary tract symptoms: Results from a phase 2, dose-finding study (saturn). Eur Urol 2013; 64: 398.
  188. Kaplan SA, Roehrborn CG, Rovner ES et al: Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: A randomized controlled trial. Jama 2006; 296: 2319.
  189. Kaplan SA, Roehrborn CG, Chancellor M et al: Extended-release tolterodine with or without tamsulosin in men with lower urinary tract symptoms and overactive bladder: Effects on urinary symptoms assessed by the international prostate symptom score. BJU Int 2008; 102: 1133.
  190. Roehrborn CG, Kaplan SA, Jones JS et al: Tolterodine extended release with or without tamsulosin in men with lower urinary tract symptoms including overactive bladder symptoms: Effects of prostate size. Eur Urol 2009; 55: 472.
  191. Roehrborn CG, Kaplan SA, Kraus SR et al: Effects of Serum PSA on Efficacy of Tolterodine Extended Release With or Without Tamsulosin in Men With LUTS, Including OAB. Urology, 2008; 72: 1061.
  192. Kim TH, Jung W, Suh YS et al: Comparison of the efficacy and safety of tolterodine 2 mg and 4 mg combined with an α-blocker in men with lower urinary tract symptoms (luts) and overactive bladder: A randomized controlled trial. BJU Int 2016; 117: 307.
  193. Richardson K, Fox C, Maidment et al: Anticholinergic drugs and risk of dementia: case-control study BMJ 2018; 361 :k1315.
  194. Coupland CAC, Hill T, Dening T et al: Anticholinergic drug exposure and the risk of dementia: a nested case-control study. JAMA Intern Med 2019; 179: 1084.
  195. van Kerrebroeck P, Chapple C, Drogendijk T et al: Combination therapy with solifenacin and tamsulosin oral controlled absorption system in a single tablet for lower urinary tract symptoms in men: Efficacy and safety results from the randomised controlled neptune trial. Eur Urol 2013; 64: 1003.
  196. Kaplan SA, McCammon K, Fincher R et al: Safety and tolerability of solifenacin add-on therapy to alpha-blocker treated men with residual urgency and frequency. J Urol 2009; 182: 2825.
  197. Memon I, Javed A, Pirzada AJ et al: Efficacy of alfuzosin with or without tolterodine, in benign prostatic hyperplasia (BPH) having irritative (overactive bladder) symptoms. RJM 2014; 39: 421.
  198. Lee SH, Chung BH, Kim SJ et al: Initial combined treatment with anticholinergics and α-blockers for men with lower urinary tract symptoms related to bph and overactive bladder: A prospective, randomized, multi-center, double-blind, placebo-controlled study. Prostate Cancer Prostatic Dis 2011; 14: 320.
  199. Chapple C, Herschorn S, Abrams P et al: Tolterodine treatment improves storage symptoms suggestive of overactive bladder in men treated with alpha-blockers. Eur Urol 2009; 56: 534.
  200. Kaplan SA. Roehrborn CG, Gong J et al: Add-on fesoterodine for residual storage symptoms suggestive of overactive bladder in men receiving α -blocker treatment for lower urinary tract symptoms. BJU Int 2011; 109: 1831.
  201. Nitti VW, Rosenberg S, Mitcheson DH et al: Urodynamics and safety of the b3-adrenoceptor agonist mirabegron in males with lower urinary tract symptoms and bladder outlet obstruction. JU 2013; 190: 1320.
  202. Matsukawa Y, Takai S, Majima T et al: Comparison in the efficacy of fesoterodine or mirabegron add-on therapy to silodosin for patients with benign prostatic hyperplasia complicated by overactive bladder: a randomized, prospective trial using urodynamic studies. Neurourol Urodyn 2019; 38: 941.
  203. Goldfischer E, Kowalcyz JJ, Clark WR et al: Hemodynamic effects of once-daily tadalafil in men with signs and symptoms of benign prostatic hyperplasia on concomitant α1-adrenergic antagonist therapy: results of a multicenter randomized, double-blind, placebo-controlled trial. Urology 2012; 79: 876.
  204. Kim SW, Park NC, Lee SW et al: Efficacy and safety of a fixed-dose combination therapy of tamsulosin and tadalafil for patients with lower urinary tract symptoms and erectile dysfunction: results of a randomized, double-blinded, active-controlled trial. JSM 2017; 14: 1018.
  205. Gacci M, Vittori G, Tosi N et al: A randomized, placebo-controlled study to assess safety and efficacy of vardenafil 10 mg and tamsulosin 0.4 mg vs. tamsulosin 0.4 mg alone in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Sex Med 2012; 9: 1624.
  206. Agrawal MS, Yadav A, Yadav H et al: A prospective randomized study comparing alfuzosin and tamsulosin in the management of patients suffering from acute urinary retention caused by benign prostatic hyperplasia. Indian J Urol 2009; 25: 474.
  207. Al-Hashimi MM: Alfuzosin 10 mg once daily in the management of acute urinary retention of benign prostatic hyperplasia. Therapy 2007; 4.
  208. Salem Mohamed SH, El Ebiary MF, Badr MM: Early versus late trail of catheter removal in patients with urinary retention secondary to benign prostatic hyperplasia under tamsulosin treatment. Urol Sci 2018; 0.
  209. Kara O, Yazici M: Is the double dose alpha-blocker treatment superior than the single dose in the management of patients suffering from acute urinary retention caused by benign prostatic hyperplasia? Urology 2014; 11: 1673.
  210. Kumar S, Tiwari DP, Ganesamoni R et al: Prospective randomized placebo-controlled study to assess the safety and efficacy of silodosin in the management of acute urinary retention. Urology 2013; 82: 171.
  211. Lucas MG, Stephenson TP, Nargund V: Tamsulosin in the management of patients in acute urinary retention from benign prostatic hyperplasia. BJU Int 2005; 95: 354.
  212. Maldonado-Avila M, Manzanilla-Garcia HA, Sierra-Ramirez JA et al: A comparative study on the use of tamsulosin versus alfuzosin in spontaneous micturition recovery after transurethral catheter removal in patients with benign prostatic growth. Int Urol Nephrol 2014; 46: 687.
  213. McNeill SA, Daruwala PD, Mitchell IDC et al: Sustained-release alfuzosin and trial without catheter after acute urinary retention: a prospective, placebo-controlled trial. BJU Int 1999; 84: 622.
  214. McNeill SA, Hargreave TB, et al: Alfuzosin once daily facilitates return to voiding in patients in acute urinary retention. Urology 2004; 171: 2316.
  215. McNeill SA, Hargreave TB, Roehrborn CG et al: Alfuzosin 10 mg once daily in the management of acute urinary retention: results of a double-blind placebo-controlled study. Urology 2005; 65: 83.
  216. Patil SB, Ranka K, Kundargi VS, et al. Comparison of tamsulosin and silodosin in the management of acute urinary retention secondary to benign prostatic hyperplasia in patients planned for trial without catheter. A prospective randomized study. Cent European J Urol 2017; 70: 259.
  217. Prieto L, Romero J, Lopez C et al: Efficacy of doxazosin in the treatment of acute urinary retention due to benign prostate hyperplasia. Urologia Internationalis 2008; 81; 66.
  218. Shah T, Palit V, Biyani S et al: Randomised, placebo controlled, double blind study of alfuzosin SR in patients undergoing trial without catheter following acute urinary retention. Eur Urol 2002; 42: 329.
  219. Sharifi SH, Mokarrar MH, Khaledi F et al: Does sildenafil enhance the effect of tamsulosin in relieving acute urinary retention? Int Braz J Urol 2014; 40: 373.
  220. Tiong HY, Tibung MJB, Macalalag M et al: Alfuzosin 10 mg once daily increases the chances of successful trial without catheter after acute urinary retention secondary to benign prostate hyperplasia. Urologia Internationalis 2009; 83: 44.
  221. Toren P, Margel D, Kulkarni G, et al: Effect of dutasteride on clinical progression of benign prostatic hyperplasia in asymptomatic men with enlarged prostate: a post hoc analysis of the REDUCE study. BMJ 2013; 346: 1.
  222. Wasson JH, Bubolz TA, Lu-Yao GL et al: Transurethral resection of the prostate among medicare beneficiaries: 1984 to 1997. J Urol 2000; 164: 1212.
  223. Malaeb BS, Yu X, McBean AM et al: National trends in surgical therapy for benign prostatic hyperplasia in the United States (2000-2008). Urology 2012; 79 :1111.
  224. Vela-Navarrete R, Gonzalez-Enguita C, Garcia-Cardoso JV et al: The impact of medical therapy on surgery for benign prostatic hyperplasia: a study comparing changes in a decade (1992-2002). BJU Int 2005; 96: 1045.
  225. Choi SY, Kim TH, Myung SC et al: Impact of changing trends in medical therapy on surgery for benign prostatic hyperplasia over two decades. Korean J Urol 2012; 53: 23.
  226. Izard J, Nickel JC: Impact of medical therapy on transurethral resection of the prostate: two decades of change. BJU Int 2011; 108: 89.
  227. Foley SJ, Soloman LZ, Wedderburn AW et al: A prospective study of the natural history of hematuria associated with benign prostatic hyperplasia and the effect of finasteride. J Urol 2000; 163: 496.
  228. Stoffel JT, Peterson AC, Sandhu JS et al: Aua white paper on nonneurogenic chronic urinary retention: Consensus definition, treatment algorithm, and outcome end points. J Urol 2017; 198: 153.
  229. Cornu JN, Ahyai S, Bachmann A et al: A systematic review and meta-analysis of functional outcomes and complications following transurethral procedures for lower urinary tract symptoms resulting from benign prostatic obstruction: an update. Eur Urol 2015; 67: 1066.
  230. Tang Y, Li J, Pu C et al: Bipolar transurethral resection versus monopolar transurethral resection for benign prostatic hypertrophy: A systematic review and meta-analysis. J Endourol 2014; 28: 1107.
  231. Omar MI, Lam TB, Alexander CE et al: Systematic review and meta-analysis of the clinical effectiveness of bipolar compared with monopolar transurethral resection of the prostate (turp). BJU Int 2014; 113: 24.
  232. Burke N, Whelan JP, Goeree L et al: Systematic review and meta-analysis of transurethral resection of the prostate versus minimally invasive procedures for the treatment of benign prostatic obstruction. Urology 2010; 75: 1015.
  233. Mamoulakis C, Ubbink DT and de la Rosette JJ: Bipolar versus monopolar transurethral resection of the prostate: A systematic review and meta-analysis of randomized controlled trials. Eur Urol 2009; 56: 798.
  234. Mebust WK, Holtgrewe HL, Cockett AT et al: Transurethral prostatectomy: immediate and postoperative complications. Cooperative study of 13 participating institutions evaluating 3,885 patients. J Urol 1989; 141: 243.
  235. Ou R, You M, Tang P et al: A randomized trial of transvesical prostatectomy versus transurethral resection of the prostate for prostate greater than 80 mL. Urology 2010; 76: 958.
  236. Simforoosh N, Abdi H, Kashi AH et al: Open prostatectomy versus transurethral resection of the prostate, where are we standing in the new era? A randomized controlled trial. Urol J 2010; 7: 262.
  237. Xie JB, Tan YA, Wang FL et al: Extraperitoneal laparoscopic adenomectomy (Madigan) versus bipolar transurethral resection of the prostate for benign prostatic hyperplasia greater than 80 ml: complications and functional outcomes after 3-year follow-up. J Endourol 2014; 28: 353.
  238. Baumert H, Ballaro A, Dugardin F et al: Laparoscopic versus open simple prostatectomy: A comparative study. J Urol 2006; 175: 1691.
  239. Porpiglia F, Terrone C, Renard J et al: Transcapsular adenomectomy(Millin): A comparative study, extraperitoneal laparoscopy versus open surgery. Eur Urol 2006; 49: 120.
  240. McCullough TC, Heldwein FL, Soon SJ et al: Laparoscopic versus open simple prostatectomy: An evaluation of morbidity. J Endourol 2009; 23: 129.
  241. Garcia-Segui A, Gascon-Mir M: Comparative study between laparoscopic extraperitoneal and open adenomectomy. Actas Urol Esp 2012; 36: 110.
  242. Demir A, Gunseren KO, Kordan Y et al: Open vs laparoscopic simple prostatectomy: A comparison of initial outcomes and cost. J Endourol 2016; 30: 884.
  243. Garcia-Segui A, Angulo JC: Prospective study comparing laparoscopic and open adenomectomy: Surgical and functional results. Actas Urol Esp 2016; 41: 47.
  244. Jinze Li, Dehong Cao, Lei Peng et al: Comparison between minimally invasive simple prostatectomy and open simple prostatectomy for large prostates: A systematic review and meta-analysis of comparative trials. J Endourol; 33: No. 9.
  245. Sorokin I, Sundaram V, Singla N et al: Robot-assisted versus open simple prostatectomy for benign prostatic hyperplasia in large glands: A propensity score-matched comparison of perioperative and short-term outcomes. J Endourol 2017; 31: 1164.
  246. Mourmouris P, Keskin SM, Skolarikos A et al: A prospective comparative analysis of robot-assisted vs open simple prostatectomy for benign prostatic hyperplasia. BJU Int 2018; 123: 313.
  247. Nestler S, Bach T, Herrmann T et al: Surgical treatment of large volume prostates: A matched pair analysis comparing the open, endoscopic (ThuVEP) and robotic approach. World J Urol 2018.
  248. Moschovas MC, Timóteo F, Lins L et al: Robotic surgery techniques to approach benign prostatic hyperplasia disease: A comprehensive literature review and the state of art. Asian J Urol 2021; 8: 81.
  249. Ganesan V, Steinberg RL, Garbens A et al: Single-port robotic-assisted simple prostatectomy is associated with decreased post-operative narcotic use in a propensity score matched analysis. J Robot Surg 2021. Online ahead of print.
  250. Reich O, Gratzke C, Stief CG: Techniques and long-term results of surgical procedures for BPH. Eur Urol 2006; 49: 970.
  251. Abd-El Kader O, Mohy El Den K, El Nashar A et al: Transurethral incision versus transurethral resection of the prostate in small prostatic adenoma: long-term follow-up. Afr J Urol 2012; 18: 29.
  252. Geavlete B, Bulai C, Ene C et al: Bipolar vaporization, resection, and enucleation versus open prostatectomy: optimal treatment alternatives in large prostate cases? J Endourol 2015; 29: 323.
  253. Elsakka A, Eltatawy H, Almekaty K et al: A prospective randomized controlled study comparing bipolar plasma vaporisation of the prostate to monopolar transurethral resection of the prostate. Arab J Urol 2017; 14: 280.
  254. Falahatkar S, Mokhtari G, Moghaddam K et al: Bipolar transurethral vaporization: a superior procedure in benign prostatic hyperplasia: a prospective randomized comparison with bipolar TURP. Int BRaz J Urol 2014; 40: 346.
  255. Geavlete B, Georgescu D, Multescu R et al: Bipolar plasma vaporization vs monopolar and bipolar TURP-A prospective, randomized, long-term comparison. Urology 2011; 78: 930.
  256. Geavlete B, Stanescu F, Moldoveanu C et al: Continuous vs conventional bipolar plasma vaporisation of the prostate and standard monopolar resection: a prospective, randomized comparison of a new technological advance. BJU Int 2014; 113: 288.
  257. Hoekstra RJ, Van Melick HH, Kok ET et al: A 10-year follow-up after transurethral resection of the prostate, contact laser prostatectomy and electrovaporization in men with benign prostatic hyperplasia; long-term results of a randomized controlled trial. BJU Int 2010; 106: 822.
  258. Karaman MI, Kaya C, Ozturk M et al: Comparison of transurethral vaporization using PlasmaKinetic energy and transurethral resection of prostate: 1-yearfollow-up. J Endourol 2005; 19: 734.
  259. Kaya C, Ilktac A, Gokmen E et al: The long-term results of transurethral vaporization of the prostate using plasmakinetic energy. BJU Int 2007; 99: 845.
  260. Koca O, Keles MO, Kaya C et al: Plasmakinetic vaporization versus transurethral resection of the prostate: six-year results. Turk J Urol 2014; 40:134.
  261. Nuhoglu B, Balci MB, Aydin M et al: The role of bipolar transurethral vaporization in the management of benign prostatic hyperplasia. Urol Int 2011; 87: 400.
  262. van Melick HH, van Venrooij GE, Eckhardt MD et al: A randomized controlled trial comparing transurethral resection of the prostate, contact laser prostatectomy and electrovaporization in men with benign prostatic hyperplasia: analysis of subjective changes, morbidity and mortality. J Urol 2003; 169:1411.
  263. van Melick HH, van Venrooij GE, Boon TA: Long-term follow-up after transurethral resection of the prostate, contact laser prostatectomy, and electrovaporization. Urology 2003; 62:1029.
  264. Zhang SY, Hu H, Zhang XP et al: Efficacy and safety of bipolar plasma vaporization of the prostate with "button-type" electrode compared with transurethral resection of prostate for benign prostatic hyperplasia. Chin Med J (Engl) 2012; 125: 3811.
  265. Ekengren J, Haendler L, Hahn RG. Clinical outcome 1 year after transurethral vaporization and resection of the prostate. Urology 2000; 55: 231.
  266. Hammadeh MY, Fowlis GA, Singh M, Philp T: Transurethral eletrovaporization of the prostate-a possible alternative to transurethral resection: a one year follow-up of a prospective randomized trial. Br J Urol 1998; 81: 721.
  267. Hammadeh MY, Madaan S, Singh M et al: A 3-year follow up of a prospective randomized trial comparing transurethral electrovaporization of the prostate with standard transurethral prostatectomy. BJU Int 2000; 86: 648.
  268. McAllister WJ, Karim O, Samra DR et al: Transurethral electrovaporization of the prostate: is it any better than conventional transurethral resection of the prostate? BJU Int 2003; 91: 211.
  269. Fowler C, McAllister W, Plail R et al: Randomized evaluation of alternative electrosurgical modalities to treat bladder outflow obstruction in mean with benign prostatic hyperplasia. Health Technol Assess 2005; 9: 1.
  270. Nuhoglu B, Ayyildiz A, Fidan V et al: Transurethral electrovaporization of the prostate: is it any better than standard transurethral prostatectomy? 5-year follow up. J Endourol 2005; 19: 79.
  271. Erdagi U, Akman RY, Sargin SY et al: Transurethral electrovaporization of the prostate versus transurethral resection of the prostate: a prospective randomized study. Arch Ital Urol Androl 1999; 71: 125.
  272. Yip SK, Chan NH, Chiu P et al: A randomized controlled trial comparing the efficacy of hybrid bipolar transurethral vaporization and resection of the prostate with bipolar transurethral resection of the prostate. J Endourol 2011; 25: 1889.
  273. Gupta N, Sivaramakrishna, Kumar R et al: Comparison of standard transurethral resection, transurethral vapour resection and holmium laser enucleation of the prostate for managing benign prostatic hyperplasia of >40 g. BJU Int. 2006; 97: 85.
  274. Gupta NP, Doddamani D, Aron M et al: Vapor resection: a good alternative to standard loop resection in the management of prostates >40 cc. J Endourol 2002; 16: 767.
  275. Helke C, Manseck A, Hakenberg OW et al: Is transurethral vaporesection of the prostate better than standard transurethral resection? Eur Urol 2001; 39: 551.
  276. Kupeli S, Yilmaz E, Soygur T et al: Randomized study of transurethral resection of the prostate and combined transurethral resection and vaporization of the prostate as a therapeutic alternative in men with benign prostatic hyperplasia. J Endourol 2001; 15: 317.
  277. Perk H, Serel TA, Kosar A et al: Comparative early results of the sandwich technique and transurethral electroresection in benign prostatic hyperplasia. Prostate Cancer Prostatic Dis 2001; 4: 242.
  278. Albino G, Marucco EC: TURP and PVP treatments are really similar? From subjective feeling to objective data. Pilot study (proof of concept) prospective randomized trial. Arch Ital Urol Androl 2012; 84: 220.
  279. Bachmann A, Schürch L, Ruszat R et al: Photoselective vaporization (PVP) versus transurethral resection of the prostate (TURP): a prospective bi-centre study of perioperative morbidity and early functional outcome. Eur Urol 2005; 48: 965.
  280. Bouchier-Hayes DM: Photoselective vaporization of the prostate – towards a new standard. Prostate Cancer Prostatic Dis 2007; 10: S10.
  281. Bouchier-Hayes DM, Van Appledorn S, Bugeja P et al: A randomized trial of photoselective vaporization of the prostate using the 80-W potassium-titanyl-phosphate laser vs transurethral prostatectomy, with a 1-year follow-up. BJU Int 2010; 105: 964.
  282. Horasanli K, Silay MS, Altay B et al: Photoselective potassium titanyl phosphate (KTP) laser vaporization versus transurethral resection of the prostate for prostates larger than 70 mL: a short-term prospective randomized trial. Urology 2008; 71: 247.
  283. Mohanty NK, Vasaudeva P, Kumar A et al: Photoselective vaporization of prostate vs. transurethral resection of prostate: A prospective, randomized study with one year follow-up. Indian J Urol 2012; 28: 307.
  284. Nomura H, Seki N, Yamaguchi A et al: Comparison of photoselective vaporization and standard transurethral resection of the prostate on urodynamics in patients with benign prostatic hyperplasia. Int J Urol 2009; 16: 657.
  285. Ruszat R, Wyler SF, Seitz M et al: Comparison of potassium-titanyl-phosphate laser vaporization of the prostate and transurethral resection of the prostate: update of a prospective non-randomized two-centre study. BJU Int 2008; 102: 1432.
  286. Tasci AI, Tugcu V, Sahin S et al: Rapid communication: photoselective vaporization of the prostate versus transurethral resection of the prostate for the large prostate: a prospective nonrandomized bicenter trial with 2-year follow-up. J Endourol 2008; 22: 347.
  287. Tugcu V, Tasci AI, Sahin S et al: Comparison of photoselective vaporization of the prostate and transurethral resection of the prostate: a prospective nonrandomized bicenter trial with 2-year follow-up. J Endourol 2008; 22: 1519.
  288. Al-Ansari A,Younes N, Sampige VP et al: GreenLight HPS 120-W laser vaporization versus transurethral resection of the prostate for treatment of benign prostatic hyperplasia: a randomized clinical trial with midterm follow-up. Eur Urol 2010; 58: 349.
  289. Bowen JM, Whelan JP, Hopkins RB et al: Photoselective vaporization for the treatment of benign prostatic hyperplasia. Ont Health Technol Assess Ser 2013; 13: 1.
  290. Capitan C, Blazquez C, Martin MD et al: GreenLight HPS 120-W laser vaporization versus transurethral resection of the prostate for the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia: a randomized clinical trial with 2-year follow-up. Eur Urol 2011; 60: 734.
  291. Liatsikos E, Kyriazis I, Kallidonis P et al: Photoselective GreenLight? laser vaporization versus transurethral resection of the prostate in Greece: a comparative cost analysis. J Endourol 2012; 26: 168.
  292. Lukacs B, Loeffler J, Bruyere F et al: Photoselective vaporization of the prostate with GreenLight 120-W laser compared with monopolar transurethral resection of the prostate: a multicenter randomized controlled trial. Eur Urol 2012; 61: 1165.
  293. Pereira-Correia JA, de Moraes Sousa KD, Santos JB et al: GreenLight HPSTM 120-W laser vaporization vs transurethral resection of the prostate (<60 mL): a 2-year randomized double-blind prospective urodynamic investigation. BJU Int 2012; 110: 1184.
  294. Telli O, Okutucu TM, Suer E et al: A prospective, randomized comparative study of monopolar transurethral resection of the prostate versus photoselective vaporization of the prostate with GreenLight 120-W laser, in prostates less than 80 cc. Ther Adv Urol 2015; 7: 3.
  295. Xue B, Zang Y, Zhang Y et al: GreenLight HPS 120-W laser vaporization versus transurethral resection of the prostate for treatment of benign prostatic hyperplasia: a prospective randomized trial. J Xray Sci Technol 2013; 21: 125.
  296. Kumar A, Vasudeva P, Kumar N et al: A prospective randomized comparative study of monopolar and bipolar transurethral resection of the prostate and photoselective vaporization of the prostate in patients who present with benign prostatic obstruction: a single center experience. J Endourol 2013; 27:1245.
  297. Kumar N, Vasudeva P, Kumar Aet al: Prospective randomized comparison of monopolar TURP, bipolar TURP and photoselective vaporization of the prostate in patients with benign prostatic obstruction: 36 months outcome. Low Urin Tract Symptoms 2018; 10: 17.
  298. Bachmann A, Tubaro A, Barber N et al: A European multicenter randomized noninferiority trial comparing 180 W GreenLight XPS laser vaporization and transurethral resection of the prostate for the treatment of benign prostatic obstruction: 12-month results of the GOLIATH study. J Urol 2015; 193: 570.
  299. Elhilali MM and Elkoushy MA: Greenlight laser vaporization versus transurethral resection of the prostate for treatment of benign prostatic obstruction: evidence from randomized controlled studies. Transl Androl Urol 2016; 5: 388.
  300. Hueber PA, Ben-Zvi T, Liberman D et al: Mid term outcomes of initial 250 case experience with GreenLight 120W-HPS Photoselective vaporization prostatectomy for benign prostatic hyperplasia: comparison of prostate volumes <60 cc, 60 cc-100 cc and > 100cc. Can J Urol 2012; 19: 6450.
  301. Rukstalis D, Grier D, Stroup SP: Prostatic Urethral Lift (PUL) for obstructive median lobes: 12 month results of the MedLift Study. Prostate Cancer Prostatic Dis 2019; 22: 411.
  302. McVary KT, Gange SN, Shore ND et al: Treatment of LUTS secondary to BPH while preserving sexual function: randomized controlled study of prostatic urethral lift. J Sex Med 2014; 11: 279.
  303. Woo HH, Bolton DM, Laborde E et al: Preservation of sexual function with the prostatic urethral lift: a novel treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Sex Med 2012; 9: 568.
  304. De la Rosette JJ, Floratos DL, Severens JL et al: Transurethral resection vs microwave thermotherapy of the prostate: a cost-consequences analysis. BJU Int 2003; 92: 713.
  305. Floratos DL, Lambertus LA, Rossi C et al: Long-term followup of randomized transurethral microwave thermotherapy versus transurethral prostatic resection study. J Urol 2001; 165: 1533.
  306. Norby B, Nielsen HV, Frimodt-Moller PC et al: Transurethral interstitial laser coagulation of the prostate and transurethral microwave thermotherapy vs transurethral resection or incision of the prostate: results of a randomized controlled study in patients with symptomatic benign prostatic hyperplasia. BJU Int 2002; 90: 853.
  307. Schelin S, Geertsen U, Walter S et al: Feedback microwave thermotherapy versus TURP/prostate enucleation surgery in patients with benign prostatic hyperplasia and persistent urinary retention: a prospective, randomized, controlled, multicenter study. Urology 2006, 68: 795.
  308. Wagrell L, Schelin S, Nordlinf J et al: Feedback microwave thermotherapy versus TURP for clinical BPH-a randomized controlled multicenter study. Urology 2002; 60; 292.
  309. Wagrell L, Schelin S, Nordlinf J et al: Three-year follow-up of feedback microwave thermotherapy versus TURP for clinical BPH: A prospective randomized multicenter study. Urology 2004; 64: 698.
  310. Mattiasson A, Wagrell L, Schelin S et al: Five-year follow-up of feedback microwave thermotherapy versus TURP for clinical BPH: a prospective randomized multicenter study. Urology 2007; 69: 91.
  311. Zhang B, Wu G, Chen C et a:. Combination of channel-TURP and ILC versus standard TURP or ILC for elderly with benign prostatic hyperplasia: a randomized prospective trial. Urol Int 2011; 87: 392.
  312. Urologix: https://www.urologix.com/clinicians/cooled-thermotherapy.php. 01/18/2021.
  313. McVary KT, Roehrborn CG, Avins AL et al: Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol 2011; 185: 1793.
  314. Naspro R, Gomez Sancha F, Manica M et al: From "gold standard" resection to reproducible "future standard" endoscopic enucleation of the prostate: what we know about anatomical enucleation. Minerva Urol Nefrol 2017; 69: 446.
  315. Habib EI, ElSheemy MS, Hossam A et al: Holmium laser enucleation versus bipolar plasmakinetic resection for management of lower urinary tract symptoms in patients with large-volume benign prostatic hyperplasia: Randomized-controlled trial. J Endourol 2020;
  316. Jhanwar A, Sinha RJ, Bansal A et al: Outcomes of transurethral resection and holmium laser enucleation in more than 60 g of prostate: A prospective randomized study. Urol Ann 2017; 9: 45.
  317. Kuntz RM, Ahyai S, Lehrich K et al: Transurethral holmium laser enucleation of the prostate versus transurethral electrocautery resection of the prostate: a randomized prospective trial in 200 patients. J Urol 2004; 172: 1012.
  318. Tan A, Gilling P, Kennett K et al: A randomized trial comparing holmium laser enucleation of the prostate with transurethral resection of the prostate for the treatment of bladder outlet obstruction secondary to benign prostatic hyperplasia in large glands (40 to 200 grams). J Urol 2003; 170: 1270.
  319. Wilson L, Gilling P, Williams A et al: A randomized trial comparing holmium laser enucleation versus transurethral resection in the treatment of prostates larger than 40 grams: results at 2 years. Eur Urol 2006; 50: 569.
  320. Chen Y, Chen Q, Wang et al: A Prospective randomized clinical trial comparing plasmakinetic resection of the prostate with holmium laser enucleation of the prostate based on a 2-year followup. J Urol 2013; 189: 217.
  321. Fayad AS, Elsheikh MG, Zakaria T et al: Holmium laser enucleation of the prostate versus bipolar resection of the prostate: a prospective randomized study. "pros and cons". Urology 2015; 86: 1037.
  322. Hamouda A, Morsi G, Habib E et al: A comparative study between holmium laser enucleation of the prostate and transurethral resection of the prostate: 12-month follow-up. Journal of Clinical Urology 2014; 7: 99.
  323. Bašić D, Stankovic J, Potic M et al: Holmium laser enucleation versus transurethral resection of the prostate: a comparison of clinical results. Acta Chir Iugosl 2013; 60: 15.
  324. Eltabey MA, Sherif H, Hussein AA: Holmium laser enucleation versus transurethral resection of the prostate. Can J Urol 2010; 17: 5447.
  325. Mavuduru RM, Mandal AK, Singh SK et al: Comparison of HoLEP and TURP in terms of efficacy in the early postoperative period and perioperative morbidity. Urol Int 2009; 82: 130.
  326. Sun N, Fu Y, Tian T et al: Holmium laser enucleation of the prostate versus transurethral resection of the prostate: a randomized clinical trial. Int Urol Nephrol 2014; 46: 1277.
  327. Cui D, Sun F, Zhuo J et al: A randomized trial comparing thulium laser resection to standard transurethral resection of the prostate for symptomatic benign prostatic hyperplasia: four-year follow-up results. World J Urol 2014; 32: 683.
  328. Yang Z, Wang X, Liu T: Thulium laser enucleation versus plasmakinetic resection of the prostate: a randomized prospective trial with 18 month follow up. Urology 2013; 81: 396.
  329. Yang Z, Liu T, Wang X: Comparison of thulium laser enucleation and plasmakinetic resection of the prostate in a randomized prospective trial with 5-year follow-up. Lasers Med Sci 2016; 31: 1797.
  330. Wei H, Shao Y, Sun F et al: Thulium laser resection versus plasmakinetic resection of prostates larger than 80 ml. World J Urol 2014; 32: 1077.
  331. Yan H, Ou TW, Chen L et al: Thulium laser vaporesection versus standard transurethral resection of the prostate: a randomized trial with transpulmonary thermodilution hemodynamic monitoring. Int J Urol 2013; 20: 507.
  332. Świniarski PP, Stępień S, Dudzic W et al: Thulium laser enucleation of the prostate (TmLEP) vs. transurethral resection of the prostate (TURP): evaluation of early results. Cent European J Urol 2012; 63: 130.
  333. Peng B, Wang G, Zheng J et al: A comparative study of thulium laser resection of the prostate and bipolar transurethral plasmakinetic prostatectomy for treating benign prostatic hyperplasia. BJU International 2012; 111: 633.
  334. Bozzini G, Seveso M, Melegari S et al: Thulium laser enucleation (ThuLEP) versus transurethral resection of the prostate in saline (TURis): a randomized prospective trial to compare intra and early postoperative outcomes. Actas Urological Espanolas 2017; 41: 309.
  335. Chang CH, Lin TP, Chang YH et al: Vapoenucleation of the prostate using a high-power thulium laser: a one-year follow-up study. BMC Urology 2015; 15: 40.
  336. Fu WJ, Zhang X, Yang Y et al: Comparison of 2-µm continuous wave laser vaporesection of the prostate and transurethral resection of the prostate: a prospective nonrandomized trial with 1-year follow-up. Urology 2010; 75: 194.
  337. Gilling P, Barber N, Bidair M et al: Water: A double-blind, randomized, controlled trial of aquablation(®) vs transurethral resection of the prostate in benign prostatic hyperplasia. J Urol 2018; 199: 1252.
  338. Gilling PJ, Barber N, Bidair M et al: Randomized controlled trial of aquablation versus transurethral resection of the prostate in benign prostatic hyperplasia: One-year outcomes. Urology 2019; 125: 169.
  339. Plante M, Gilling P, Barber N et al: Symptom relief and anejaculation after aquablation or transurethral resection of the prostate: Subgroup analysis from a blinded randomized trial. BJU Int 2019; 123: 651.
  340. Gilling P, Barber N, Bidair M et al: Two-year outcomes after aquablation compared to turp: Efficacy and ejaculatory improvements sustained. Adv Ther 2019; 36: 1326.
  341. Desai M, Bidair M, Bhojani N et al: Water ii (80-150 ml) procedural outcomes. BJU Int 2019; 123: 106.
  342. Carnevale FC, Iscaife A, Yoshinaga EM et al: Transurethral resection of the prostate (TURP) versus original and PErFecTED prostate artery embolization (PAE) due to benign prostatic hyperplasia (BPH): preliminary results of a single center, prospective, urodynamic-controlled analysis. Cardiovasc Intervent Radiol 2016; 39: 44.
  343. Gao Y, Huang Y, Zhang R et al: Benign prostatic hyperplasia: prostatic arterial embolization versus transurethral resection of the prostate—a prospective, randomized, and controlled trial. Radiology 2014; 270: 920.
  344. Abt D, Hechelhammer L, Mullhaupt G et al: Comparison of prostatic artery embolization (PAE) versus transurethral resection of the prostate (TURP) for benign prostatic hyperplasia: randomized, open label, non-inferiority trial. BMJ 2018; 361:k2338.
  345. Rastinehad AR, Ost MC, VanderBrink BA et al: Persistent prostatic hematuria. Nat Clin Pract Urol 2008; 5: 159.
  346. Kirby R: A randomized, double-blind crossover study of tamsulosin and controlled-release doxazosin in patients with benign prostatic hyperplasia. BJU Int 2003; 91: 41.
  347. Pompeo A, Rosenblatt C, Bertero E et al: A randomised, double-blind study comparing the efficacy and tolerability of controlled-release doxazosin and tamsulosin in the treatment of benign prostatic hyperplasia in Brazil. Int J Clin Pract 2006; 60: 1172.
  348. Samli M, Dincel C: Terazosin and doxazosin in the treatment of BPH: results of a randomized study with crossover in non-responders. Urol Int 2004; 73: 125.
  349. Baldwin K, Ginsberg P, Roehrborn C et al: Discontinuation of alpha-blockade after initial treatment with finasteride and doxazosin in men with lower urinary tract symptoms and clinical evidence of benign prostatic hyperplasia. Urology 2001; 58: 203.
  350. Fawzy A, Hendry A, Cook E et al: Long-term (4 year) efficacy and tolerability of doxazosin for the treatment of concurrent benign prostatic hyperplasia and hypertension. Int J Urol 1999; 6: 346.
  351. Chung B, Hong S: Long-term follow-up study to evaluate the efficacy and safety of the doxazosin gastrointestinal therapeutic system in patients with benign prostatic hyperplasia with or without concomitant hypertension. BJU Int 2006; 97: 90.
  352. De Rose A, Carmignani G, Corbu C et al: Observational multicentric trial performed with doxazosin: evaluation of sexual effects on patients with diagnosed benign prostatic hyperplasia. Urol Int 2002; 68: 95.
  353. Ozdal OL, Ozden C, Benli K et al: Effect of short-term finasteride therapy on peroperative bleeding in patients who were candidates for transurethral resection of the prostate (tur-p): A randomized controlled study. Prostate Cancer Prostatic Dis 2005; 8: 215.
  354. Tapping CR, Macdonald A, Hadi M et al: Prostatic artery embolization (pae) for benign prostatic hyperplasia (bph) with haematuria in the absence of an upper urinary tract pathology. Cardiovasc Intervent Radiol 2018; 41: 1160.
  355. Mavuduru RM, Mandal AK, Singh SK, et al. Comparison of HoLEP and TURP in terms of efficacy in the early postoperative period and perioperative morbidity. Urologia Internationalis. 2009;82(2):130-135.
  356. Montorsi F, Naspro R, Salonia A et al: Holmium laser enucleation versus transurethral resection of the prostate: results from a 2-center, prospective, randomized trial in patients with obstructive benign prostatic hyperplasia. J Urol 2004; 172: 1926.
  357. Xia SJ, Zhuo J, Sun XW et al: Thulium laser versus standard transurethral resection of the prostate: a randomized prospective trial. Euro Urol 2008; 53: 382.
  358. Bishop CV, Liddell H, Ischia J et al: Holmium laser enucleation of the prostate: comparison of immediate postoperative outcomes in patients with and without antithrombotic therapy. Curr Urol 2013; 7: 28.
  359. El Tayeb MM, Jacob JM, Bhojani N et al: Holmium laser enucleation of the prostate in patients requiring anticoagulation. J Endourol 2016; 30: 805.
  360. Gravas S, Bach T, Drake M, Gacci M, Gratzke C, Herrmann T.R.W. Madersbacher S, Mamoulakis C, Tikkinen K.A.O. Management of Non-Neurogenic Male Lower Urinary Tract Symptoms (LUTS), incl.Benign Prostatic Obstruction (BPO) Edn. presented at the EAU Annual Congress London 2017. 978-90-79754-91-5. Publisher: EAU Guidelines Office. Place published: Arnhem, The Netherlands.
  361. Elzayat E., Habib E, Elhilali M: Holmium laser enucleation of the prostate in patients on anticoagulant therapy or with bleeding disorders. J Urol 2006; 175: 1428.
  362. Rivera M, Krambeck A, Lingeman J: Holmium laser enucleation of the prostate in patients requiring anticoagulation. Curr Urol Rep 2017; 18: 77.
  363. Macchione L, Mucciardi G, Gali' A et al: Efficacy and safety of prostate vaporesection using a 120-W 2-μm continuous-wave Tm:YAG laser (RevoLix 2) in patients on continuous oral anticoagulant or antiplatelet therapy. Int Urol Nephrol 2013; 45: 1545.
  364. Descazeaud A, Robert G, Azzousi AR et al: Committee for lower urinary tract symptoms of the French Association of Urology. Laser treatment of benign prostatic hyperplasia in patients on oral anticoagulant therapy: a review. BJU Int 2009; 103: 1162.
  365. Netsch C, Stoehrer M, Brüning M et al: Safety and effectiveness of thulium vapoenucleation of the prostate (ThuVEP) in patients on anticoagulant therapy. World J Urol 2014; 32: 165.
  366. Sener TE, Butticè S, Macchione L et al: Thulium laser vaporesection of the prostate: Can we operate without interrupting oral antiplatelet/anticoagulant therapy? Investig Clin Urol 2017;58: 192.
  367. Lee DJ, Rieken M, Halpern J et al: Laser vaporization of the prostate with the 180-W XPS-Greenlight laser in patients with ongoing platelet aggregation inhibition and oral anticoagulation. Urology 2016; 91: 167.
  368. Woo HH, Hossack TA: Photoselective vaporization of the prostate with the 120-W lithium triborate laser in men taking coumadin. Urology 2011; 78: 142.
  369. Ruszat R, Wyler S, Forster T et al: Safety and effectiveness of photoselective vaporization of the prostate (PVP) in patients on ongoing oral anticoagulation. Eur Urol 2007; 51:1031.
  370. Brassetti A, DE Nunzio C, Delongchamps NB et al: Green light vaporization of the prostate: is it an adult technique? Minerva Urol Nefrol 2017; 69: 109.
  371. Knapp GL, Chalasani V, Woo HH: Perioperative adverse events in patients on continued anticoagulation undergoing photoselective vaporisation of the prostate with the 180-W Greenlight lithium triborate laser. BJU Int 2017; 119: 33.
  372. Anticoagulation and Antiplatelet Therapy in Urologic Practice: ICUD and AUA Review Paper 2014. http://www.auanet.org/guidelines/anticoagulation-and-antiplatelet-therapy.
  373. (Institute of Medicine (US) Committee on Understanding and Eliminating Racial and Ethnic Disparities in Health Care. Unequal treatment: confronting racial and ethnic disparities in health care. Smedley BD, Stith AY, Nelson AR, editors. Washington (DC): National Academies Press (US); 2003.

Abbreviations

5-Alpha Reductase Inhibitor5-ARI
95 Percent Confidence Interval95%CI
Acute Urinary RetentionAUR
American Urological AssociationAUA
AUA-Symptom IndexAUA-SI
Benign Prostatic EnlargementBPE
Benign Prostatic HyperplasiaBPH
Benign Prostatic ObstructionBPO
Benign Outlet ObstructionBOO
Clinical Controlled TrialsCCT
Computed TomographyCT
DihydrotestosteroneDHT
Ejaculatory DysfunctionEjD
Erectile DysfunctionED
Erectile FunctionEF
Global Subjective AssessmentGSA
Holmium Laser Enucleation of the ProstateHoLEP
International Index of Erectile FunctionIIEF
Intraoperative Floppy Iris SyndromeIFIS
International Prostate Symptom ScoreIPSS
Laparoscopic Simple Prostatectomy/EnucleationLSP
Low Molecular Weight HeparinLMWH
Lower Urinary Tract SymptomsLUTS
Male Lower Urinary Tract Symptoms Secondary/attributed to BPHLUTS/BPH
Magnetic Resonance ImagingMRI
Medical Therapy of Prostatic SymptomsMTOPS
Minimally Detectable DifferenceMDD
Minimally Invasive Surgical TherapiesMIST
Open Simple ProstatectomyOSP
Overactive BladderOAB
Patient Perception of Study MedicationPPMS
Phosphodiesterase-5PDE5
Phosphodiesterase-5 InhibitorPDE5
Photoselective Vaporization of the ProstatePVP
Post Void ResidualPVR
Prostate Artery EmbolizationPAE
Prostate Specific AntigenPSA
Prostatic Urethral LiftPUL
Quality of LifeQoL
Randomized Controlled TrialsRCT
Retrograde EjaculationRE
Risk of BiasROB
Risk RatioRR
Robotic-Assisted Laparoscopic Simple ProstatectomyRASP
Robotic Waterjet TreatmentRWT
Thulium Laser Enucleation of the ProstateThuLEP
Thulium Laser Enucleation of the ProstateThuLEP
Transurethral Incision of the ProstateTUIP
Transurethral Incision of the ProstateTUIP
Transurethral Needle AblationTUNA
Transurethral Resection of the ProstateTURP
Transurethral UltrasoundTRUS
Transurethral Vaporization of the ProstateTUVP
Trial Without CatheterTWOC
Urinary Tract InfectionsUTI
Water Vapor Thermal TherapyWVTT
Weighted Mean DifferenceWMD

 
 

Disclaimer

This document was written by the Benign Prostatic Hyperplasia Guideline Panel of the American Urological Association Education and Research, Inc., which was created in 2016. The Practice Guidelines Committee (PGC) of the AUA selected the committee chair. Panel members were selected by the chair. Membership of the Panel included specialists in urology and primary care with specific expertise on this disorder. The mission of the panel was to develop recommendations that are analysis based or consensus-based, depending on panel processes and available data, for optimal clinical practices in the surgical treatment of benign prostatic hyperplasia. Funding of the panel was provided by the AUA. Panel members received no remuneration for their work. Each member of the panel provides an ongoing conflict of interest disclosure to the AUA. While these guidelines do not necessarily establish the standard of care, AUA seeks to recommend and to encourage compliance by practitioners with current best practices related to the condition being treated. As medical knowledge expands and technology advances, the guidelines will change. Today these evidence-based guidelines statements represent not absolute mandates but provisional proposals for treatment under the specific conditions described in each document. For all these reasons, the guidelines do not pre-empt physician judgment in individual cases. Treating physicians must take into account variations in resources, and patient tolerances, needs, and preferences. Conformance with any clinical guideline does not guarantee a successful outcome. The guideline text may include information or recommendations about certain drug uses ('off label') that are not approved by the Food and Drug Administration (FDA), or about medications or substances not subject to the FDA approval process. AUA urges strict compliance with all government regulations and protocols for prescription and use of these substances. The physician is encouraged to carefully follow all available prescribing information about indications, contraindications, precautions and warnings. These guidelines and best practice statements are not in-tended to provide legal advice about use and misuse of these substances. Although guidelines are intended to encourage best practices and potentially encompass available technologies with sufficient data as of close of the literature review, they are necessarily time-limited. Guidelines cannot include evaluation of all data on emerging technologies or management, including those that are FDA-approved, which may immediately come to represent accepted clinical practices. For this reason, the AUA does not regard technologies or management which are too new to be addressed by this guideline as necessarily experimental or investigational.

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