Management of Benign Prostatic Hyperplasia/ Lower Urinary Tract Symptoms (2021)Panel MembersJ. 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 Show
Guideline StatementsPurposeBenign 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. MethodologyFor 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 StatementsEvaluation Initial Evaluation
Follow-up Evaluation
Preoperative Testing
Medical Therapy Alpha Blockers
Alpha Blockers and Intraoperative Floppy Iris Syndrome (IFIS)
5- Alpha Reductase inhibitor (5-ARI)
Phosphodiesterase-5 Inhibitor (PDE5)
Combination Therapy
Acute Urinary Retention (AUR) Outcomes
Surgical Therapy
Transurethral Resection of the Prostate (TURP)
Simple Prostatectomy
Transurethral Incision of the Prostate (TUIP)
Transurethral Vaporization of the Prostate (TUVP)
Photoselective Vaporization of the Prostate (PVP)
Prostatic Urethral Lift (PUL)
Transurethral Microwave Therapy (TUMT)
Water Vapor Thermal Therapy (WVTT)
Transurethral Needle Ablation (TUNA)
Laser Enucleation
Robotic Waterjet Treatment (RWT)
Prostate Artery Embolization (PAE)
Hematuria
Medically Complicated Patients
IntroductionPurposeBPH 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. MethodologyThe 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.
BackgroundBPH 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 NutraceuticalsThis 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. LUTSIn 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-SIThe 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 Treatment IndicationsTo 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 PatientFor 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:
Sexual Dysfunction and Surgical TherapyData 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-MakingIt 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. EvaluationInitial EvaluationGuideline Statement 11. 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 22. 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 EvaluationGuideline Statement 33. 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 44. 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 TestingGuideline Statement 55. 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 66. Clinicians should perform a PVR assessment prior to intervention for LUTS/BPH. (Clinical Principle) Discussion Guideline Statement 77. Clinicians should consider uroflowmetry prior to intervention for LUTS/BPH. (Clinical Principle) Discussion Guideline Statement 88. Clinicians should consider pressure flow studies prior to intervention for LUTS/BPH when diagnostic uncertainty exists. (Expert Opinion) Discussion Guideline Statement 99. 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 TherapyAlpha BlockersGuideline Statement 1010. 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 1111. 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 1212. 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 1313. 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 1414. 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 1515. 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 1616. 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 1717. 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 TherapyGuideline Statement 1818. 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 1919. 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 2020. 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 2121. 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 OutcomesGuideline Statement 2222. 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 2323. 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 2424. 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 TherapyGuideline Statement 2525. 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 2626. 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 2727. TURP should be offered as a treatment option for patients with LUTS/BPH. (Moderate Recommendation; Evidence Level: Grade B) Discussion Guideline Statement 2828. 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 ProstatectomyGuideline Statement 2929. 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 3030. 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 3131. 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 3232. 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 3333. 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 3434. 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 3535. 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 3636. 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 3737. 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 3838. TUNA is not recommended for the treatment of LUTS/BPH. (Expert Opinion) Discussion Laser EnucleationGuideline Statement 3939. 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 4040. 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 4141. 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 HematuriaGuideline Statement 4242. 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 PatientsGuideline Statement 4343. HoLEP, PVP, and ThuLEP should be considered as treatment options in patients who are at higher risk of bleeding. (Expert Opinion) Discussion Future DirectionsBPH 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 ResourcesReferences
References Abbreviations
DisclaimerThis 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. IntroductionBenign prostatic hyperplasia (BPH) is a histologic diagnosis that refers to the proliferation of smooth muscle and epithelial cells within the prostatic transition zone.1, 2 The exact etiology is unknown; however, the similarity between BPH and the embryonic morphogenesis of the prostate has led to the hypothesis that BPH may result from a "reawakening" in adulthood of embryonic induction processes. The enlarged gland has been proposed to contribute to the overall lower urinary tract symptoms (LUTS) complex via at least two routes: (1) direct bladder outlet obstruction (BOO) from enlarged tissue (static component) and (2) from increased smooth muscle tone and resistance within the enlarged gland (dynamic component). Voiding symptoms have often been attributed to the physical presence of BOO. Detrusor overactivity is thought to be a contributor to the storage symptoms seen in LUTS.3 This Guideline attempts to globally encompass the concept of LUTS in a broad spectrum of etiologies, and focuses treatment (e.g., active surveillance, medical and surgical) on the management of such symptoms. The prevalence and the severity of LUTS in the aging male can be progressive, and is an important diagnosis in the healthcare of our patients and the welfare of society. 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 American Urological Association (AUA) Symptom Index (SI) score of ≥7.4 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 acute urinary retention (AUR) as a symptom of BPH progression, increasing from a prevalence of 6.8 episodes per 1000 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.5 Although LUTS secondary to BPH (LUTS/BPH) is not often a life-threatening condition, the impact of LUTS/BPH on quality of life (QoL) can be significant and should not be underestimated.4 When the effect of BPH-associated LUTS on QoL was studied in a number of community-based populations, for many, the most important motivations for 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.6 Traditionally, the primary goal of treatment has been to alleviate bothersome LUTS that result from prostatic enlargement. More recently, treatment has additionally been focused on the alteration of disease progression and prevention of complications that can be associated with BPH/LUTS.7 A variety of pharmacologic classes are employed including alpha-adrenergic antagonists (alpha-blockers), 5-alpha- reductase inhibitors (5-ARIs), anticholinergics and phytotherapeutics. Choosing the correct medical treatment for BPH is truly complex and ever-changing. In the management of bothersome LUTS, it is important as healthcare providers that we recognize the complex dynamics of the bladder, bladder neck, prostate and urethra, and that symptoms may result from interactions of these organs as well as with the central nervous system. It is the hope that this revised clinical Guideline will provide a useful reference on the effective evidence-based management of male LUTS secondary to BPH. This 2010 Guideline reviews a number of important aspects in the management of LUTS presumed secondary to BPH including available diagnostic tests to identify the underlying pathophysiology and to assist in symptom management. Pharmacotherapies-- including complementary and alternative medications (CAM) and watchful waiting, as well as lifestyle issues-- are addressed. The current literature on the standard surgical options as well as on minimally invasive procedures was similarly reviewed. Despite the rigorous methodology and detail used in these various areas, supporting high-quality data (i.e., randomized controlled trials) could not be identified for some topics. In these situations, the Panel, not surprisingly, was forced to suggest best practices based on expert opinion. In more recent years, the association between LUTS and erectile dysfunction (ED) has been clarified. Lifestyle factors – such as exercise, weight gain and obesity –appear to have an impact on LUTS. We expect these concerns to grow in importance with the aging of our nation and the obesity epidemic. Because prevalence of LUTS increases with age, the burden and number of men complaining of LUTS will rise with the increasing life expectancy and growth of our elderly population. This will place increased demands for treatment services, and necessitate the incorporation of evidence-based medicine in treatment therein. Definitions and TerminologyFor this Guideline, the Index Patient is a male aged 45 or older who is consulting a qualified healthcare provider 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. Although the Index Patient defined in the 2003 Guideline was aged 50 or older, the Panel has lowered the age for inclusion in this Guideline, as this lower age group can present with LUTS. LUTS include storage and/or voiding disturbances common in aging men. Storage symptoms are experienced during the storage phase of the bladder and include daytime frequency and nocturia; voiding symptoms are experienced during the voiding phase. LUTS may be due to structural or functional abnormalities in one or more parts of the lower urinary tract that comprises the bladder, bladder neck, prostate, distal sphincter mechanism, and urethra. Of note, LUTS may result from abnormalities of the peripheral and/or central nervous systems that provide neural control to the lower urinary tract. LUTS may also be secondary to cardiovascular, respiratory or renal dysfunction or disease. Thus, this disease entity is particularly complex to evaluate, survey and treat. In men, enlargement of the prostate gland from hyperplasia can cause BOO and be a major cause of LUTS or mimicked by other issues, such as infection, malignancy, central-peripheral neurologic disease or overactivity/hypoactivity of detrusor muscles. In the past, a number of terms have been used to describe these LUTS in the male. These have varied from BPH, clinical BPH, BOO, prostate enlargement, or prostatism. It is becoming widely accepted that the symptom we relate in many older males may not have an etiology in prostate enlargement. For that reason, the term "LUTS independent of BPH" has been introduced and is gaining worldwide acceptance. Regardless, the concept of LUTS secondary to BPH (LUTS/BPH) is meaningful to clinicians. Less frequently, LUTS/BPH has been associated with other comorbidities including AUR, renal insufficiency, and the development of gross hematuria, bladder calculi, urinary incontinence and recurrent urinary tract infection (UTI).8, 9 The overactive bladder syndrome is defined as urgency with or without urge incontinence, usually with frequency and nocturia. Detrusor overactivity is a urodynamic observation characterized by involuntary detrusor contractions during the filling phase. These contractions may be spontaneous or provoked. The term "benign prostatic hyperplasia" is reserved for the histological pattern it describes. Benign prostatic enlargement is used when there is gland enlargement and is usually a presumptive diagnosis based on the size of the prostate. Benign prostatic obstruction (BPO) is used when obstruction has been proven by pressure flow studies, or is highly suspected from flow rates and if the gland is enlarged. Bladder outlet obstruction (BOO) is the generic term for all forms of obstruction to the bladder outlet (e.g., urethral stricture) including BPO. The AUA-SI and the International Prostate Symptom Score (I-PSS) (Appendix A6)10, 11 are nearly identical, validated short, self-administered questionnaires, used to assess the severity of three storage symptoms (frequency, nocturia, urgency) and four voiding symptoms (feeling of incomplete emptying, intermittency, straining, and a weak stream). The I-PSS also assesses the degree of bother associated with the seven symptoms in the aforementioned symptom severity score with one additional QoL question: "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?" A three-point improvement in the AUA-SI is considered meaningful. For consistency in this Guideline, the term "AUA-SI" will be used when discussing the tools unless specifically differentiated in a study being cited. The BPH Impact Index (BII) (Appendix A5) is a questionnaire that assesses the effect of symptoms on everyday life and their interference with daily activities, thus capturing the impact of the condition. This questionnaire can be administered in conjunction with the AUA-SI and provides useful additional information to the single QoL question. This Guideline does not apply when other disease pathologies are known to be responsible for LUTS, such as prostate cancer or other genitourinary tract malignancies, or when LUTS are due to significant comorbidities (e.g., severe diabetes mellitus or neurologic disease), concomitant medications, UTIs, prior pelvic surgery, or trauma. In addition to being responsible for the symptoms, these excluded clinical scenarios, diseases and/or conditions may affect treatment in a manner outside the purview of this Guideline. MethodologyThe clinical guideline statements presented in this document were based on a systematic review and synthesis of the clinical literature on current and emerging therapies for the treatment of BPH. The methodology followed the same process used in the development of the 2003 Guideline and, as such, did not include an evaluation of the strength of the body of evidence as will be instituted in future Guidelines produced by the AUA. View the full description of the methodology presented in Chapter 2. The expert Panel examined three overarching key questions for pharmacotherapeutic, surgical and alternative medicine therapies: (1) What is the comparative efficacy (the extent to which an intervention produces a beneficial result under ideal conditions such as clinical trials) and effectiveness (the extent to which an intervention in ordinary conditions produces the intended result) of currently available and emerging treatments for BPH? What are the predictors of beneficial effects from treatments? (2) What are the adverse events associated with each of the included treatments, and how do the adverse events compare across treatments? (3) Are there subpopulations in which the efficacy, effectiveness, and adverse event rates vary from those in general populations? The guideline statements were drafted by the Panel based on the outcomes data and tempered by the Panel's expert opinion. As in the previous Guideline, statements were graded using three levels with respect to the degree of flexibility in their application. A "standard" has the least flexibility as a treatment policy; a "recommendation" has significantly more flexibility; and an "option" is even more flexible. These three levels of flexibility are defined as follows: 1. Standard: A guideline statement is a standard if: (1) the health outcomes of the alternative interventions are sufficiently well known to permit meaningful decisions and (2) there is virtual unanimity about which intervention is preferred. 2. Recommendation: A guideline statement is a recommendation if: (1) the health outcomes of the alternative intervention are sufficiently well known to permit meaningful decisions, and (2) an appreciable but not unanimous majority agrees on which intervention is preferred. 3. Option: A guideline statement is an option if: (1) the health outcomes of the interventions are not sufficiently well known to permit meaningful decisions, or (2) preferences are unknown or equivocal. Options can exist because of insufficient evidence or because patient preferences are divided and may/should influence choices made. The guideline was examined by 69 peer reviewers, and approved by the Practice Guidelines Committee and the Board of Directors of the AUA. The Guideline is published on the AUA website. A summary version of the Guideline will be published in The Journal of Urology. Diagnostic EvaluationThe Panel decided that the diagnostic section of the 2003 Guideline required updating. After review of the recommendations for diagnosis published by the 2005 International Consultation of Urologic Diseases12 and reiterated in 2009 in an article by Abrams et al (2009), the Panel unanimously agreed that the contents were valid and reflected "best practices". 13 The diagnostic guidelines by Abrams et al (2009) are revisited in Appendix A7. 13 Two treatment algorithms, one on the basic management of LUTS in men and one on the detailed management for persistent bothersome LUTS —were adapted for this Guideline and are included in Appendix A1 as Figures 1.1 and 1.2, respectively. 13 Guideline StatementsFuture ResearchGiven the increasing aging male population, the health burden of benign prostate disorders such as BPH, will be a major arena for research in the future. Therefore, there is a substantial need to develop a long-range vision to focus and promote efforts to better understand and manage benign prostate disease.102 In 2010, the AUA launched an initiative to identify national research priorities in urology. Known as the AUA Foundation National Urology Research Agenda (NURA), this document defines the top issues facing urology, and BPH is identified as an area for scientific opportunity.103 The authors cite the relationship between BPH and co-morbidities as a high priority as well as a more objective method for diagnosing BPH. Inflammation of the prostate is an important area of study, and the role of diet, lifestyle, and sociodemographics on BPH is important. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) convened a panel of key opinion leaders that included basic researchers, translational scientists, epidemiologists, and clinicians and clinical researchers to develop a comprehensive strategic plan for advancing research in benign prostate disease.102 This focused group of research and thought leaders identified four major areas of key significance for future investigation: (1) basic science, (2) epidemiology/population-based studies, (3) translational opportunities, and (4) clinical sciences. The following represents a synopsis of their findings and recommendations of the NIDDK Prostate Research Strategic Plan.102 There are a host of major clinical opportunities in the future with respect to clinical science development in BPH. This includes: 1. Defining the clinical phenotype: definitions and their importance 2. Measuring disease severity and outcomes 3. Issues in clinical trial design a. Study concepts for drug therapy, phytotherapies, behavioral and lifestyle interventions 4. Additional intervention therapies. These chosen topics illustrate the pressing need for improved methods to diagnose and measure disease symptoms, severity and progression; development of new drug therapies, derived from both synthetic and naturally occurring compounds; and identification and clinical testing of prevention strategies; and for further development of intervention therapies based on non- or minimally invasive approaches. It is anticipated that progress in these areas has the potential to advance clinical care for patients with benign prostate disease beyond current strategies of symptom management, which in many cases are incompletely effective for the individual patient and are not generally effective across patients classified as having the same disorder. High Priority Recommendations for Future Research:
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Baumert H, Ballaro A, Dugardin F et al: Laparoscopic versus open simple prostatectomy: a comparative study. J Urol 2006; 175: 1691. 102. Mullins C, Kaplan S: A new vision for the study of benign prostate disease: the NIDDK prostate research strategic plan. J Urol 2009; 181: 963. 103. NURA: National Urology Research Agenda: American Urological Assocation Foundation, 2010 Which of the following is an accurate summary of the selective incorporation doctrine?Which of the following is an accurate summary of the selective incorporation doctrine? decided selectively. States must protect most rights in the Bill of Rights based on the Fourteenth Amendment's due process clause. The Supreme Court is cautious about which civil liberties cases it accepts.
Which statement best describes the system of selective incorporation?Which statement BEST describes the system of selective incorporation? a process by which the Supreme Court has affirmed that almost all the protections in the Bill of Rights may be applied to state laws.
What is the process of selective incorporation?Selective incorporation is the process in which the Supreme Court of the United States ensures that the rights guaranteed in the Constitution are not violated by the states. This is done through rulings on court cases that deal in rights violations.
When has selective incorporation been used?Ultimately, the Court adopted the selective incorporation doctrine in the 1937 case of Palko v. Connecticut. That decision rejected total incorporation and established a selective incorporation definition and guidelines for applying it.
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Which of the following statements regarding the timeline of selective incorporation are accurate
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