AUA Guideline on Management of Benign Prostatic Hyperplasia (2003). Chapter 1: Diagnosis and Treatment Recommendations

You have accessJournal of UrologyCLINICAL UROLOGY: Special Communications1 Aug 2003AUA Guideline on Management of Benign Prostatic Hyperplasia (2003). Chapter 1: Diagnosis and Treatment Recommendationsis corrected byERRATA AUA PRACTICE GUIDELINES COMMITTEE AUA PRACTICE GUIDELINES COMMITTEE More articles by this author View All Author Informationhttps://doi.org/10.1097/01.ju.0000078083.38675.79AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Benign prostatic hyperplasia (BPH), one of the most common diseases of aging men, 1 can be associated with bothersome lower urinary tract symptoms (LUTS) that affect quality of life by interfering with normal daily activities and sleep patterns. The prevalence of histopathologic BPH is age dependent, with initial development usually after 40 years of age. 2 By 60 years of age, its prevalence is greater than 50% and by age 85 it is as high as 90%. Similar to that of histologic evidence, the prevalence of bothersome symptoms also increases with age. Approximately half of all men who have a histologic diagnosis have moderate to severe LUTS. 1 Because long-term data from population-based studies have only recently become available, the risks of developing complications and morbidities from untreated BPH are unclear. For example, despite recent evidence, there is still uncertainty regarding the likelihood that a patient with a specific symptom complex will develop complete urinary retention within a particular time frame. Nonetheless, BPH associated mortality is rare in the United States, and serious complications are uncommon. In contrast, LUTS are bothersome to many patients, and the amount of bother may differ greatly among individuals with the same degree of symptom frequency and severity. 3 Since the impact of LUTS on the patient’s quality of life is highly variable and not directly related to any measurable physiological factors, the patient’s perception of the severity of the condition, as well as the degree to which it interferes with his lifestyle or causes embarrassment, should be the primary consideration in choosing therapy. 4,5 In the past decade, there have been significant changes in the available treatment options for BPH. New forms of medical and minimally invasive treatments have been approved by the United States Food and Drug Administration (FDA) while other therapies have become obsolete. This update of the 1994 AHCPR benign prostatic hyperplasia clinical practice guideline produced by the Agency for Health Care Policy and Research of the United States Department of Health and Human Services (AHCPR; now known as the Agency for Healthcare Research and Quality) was developed by a panel of experts (hereafter the Panel) chosen by the American Urological Association (AUA) Practice Guidelines Committee. Using an evidence-based approach, the multidisciplinary Panel focused on providing scientifically based information on currently available BPH treatment modalities. Because the Panel strongly believes that the patient should play a central role in determining his need for treatment, it set out to address the issue of whether or not there was sufficient evidence for outcomes (both benefits and risks) to be estimated. Thus, this guideline is intended to provide scientifically based information on treatment outcomes so that physicians can assist their patients in making appropriate treatment decisions. DEFINITIONS AND TERMINOLOGY Benign prostatic hyperplasia is defined histologically as a disease process characterized by stromal and epithelial cell hyperplasia beginning in the periurethral zone of the prostate. 6,7 The chief complaint of the patient with BPH is usually bothersome LUTS typified by urinary frequency, urgency, nocturia, decreased and intermittent force of stream and the sensation of incomplete bladder emptying. The relationship between BPH and LUTS is complex, however, because not all men with histological evidence of BPH will develop LUTS. In addition, LUTS are neither specific to nor exclusive of BPH; other conditions in the lower urinary tract and elsewhere may be causative. Moreover, not all patients with BPH and LUTS will have prostate enlargement, and prostate enlargement may exist in the absence of LUTS. The 4th International Consultation on BPH recommended the use of the general terminology LUTS or “LUTS suggestive of BPH” in place of the older term “prostatism” until a cause-and-effect BPH-symptom relationship has been established. 8 Recognizing the complexities of this nomenclature, the Panel decided that the term “BPH” would be used in this document when referring to any symptomatic conditions characterized by bothersome LUTS attributed to histological hyperplasia or increased tone of the prostate. METHODOLOGY As in the development of the 1994 AHCPR guideline, a systematic literature review was conducted based on the results of a MEDLINE® search. The search, which spanned the years from 1991 through early 2000, was supplemented with additional references from Panel members and additional data obtained from authors to explicate data previously published. The Panel chairmen reviewed the search results, and data were extracted to forms and entered into databases from which evidence tables were generated. After review by the Panel, some studies were excluded from additional analysis because of lack of relevance or quality problems. The Panel had two principal tasks: • to determine whether or not there was convincing scientific evidence that the benefits of a given treatment option (primarily symptom improvement) outweighed the risks (adverse events); and • to explicitly define the primary outcomes of the recommended treatment options to assist patients and physicians in an informed decision-making process. The Panel also outlined recommendations for future clinical research priorities Data on efficacy and safety of the following BPH treatments were reviewed: watchful waiting, alpha-adrenergic blocker therapy, 5 alpha-reductase inhibitor therapy, transurethral microwave heat treatment, transurethral needle ablation (TUNA®), interstitial laser therapy, stents, and various forms of transurethral surgery and open surgery. In addition, data on emerging transurethral heat-based technologies and high-intensity focused ultrasound (HIFU) were examined. The published literature on phytotherapy was also evaluated, although there were few randomized clinical trials of suitable duration to allow comment. Detailed analysis of study outcomes using a variety of meta-analytic techniques was performed, and outcomes tables were created for Panel review. Treatment recommendations were based on these outcomes tables and tempered by the Panel’s expert opinion. Key evidence for some interventions became available after the outcomes analysis was complete. The Panel directly reviewed these data and agreed that the new information should be considered for inclusion in the guideline. Thus, evidence from several studies support recommendations made by Panel consensus; however, these data are not presented as outcomes estimates. Of note, FDA approval alone was not sufficient to justify a positive recommendation in this guideline. First, FDA approval may be requested by a manufacturer for a non-BPH indication because a specific BPH indication may be more complicated and expensive to attain. Second, FDA approval may precede the publication of key pivotal studies, precluding Panel analysis. Third, FDA approval once given does not imply that the intervention is still currently recommended or even available (e.g., balloon dilation). Finally, the FDA may have approved a treatment that the Panel believes is not appropriate given the other available treatment options. This guideline was drafted, reviewed by the Panel, then examined by 58 peer reviewers, and finally approved by the Practice Guidelines Committee and the Board of Directors of the AUA. A full description of the methodology is presented in Chapter 2 and in the Methodologic Appendix of this guideline (http://www.auanet.org). As in the 1994 AHCPR guideline, the Panel generated recommendations based on the strength of the evidence for both diagnostic and treatment modalities and the expected amount of variation in patient preferences for treatments. In some cases, recommendations were supported solely by the Panel’s expert opinion and are designated as such in the text. For diagnostic tests, the Panel utilized the terms “recommended,” “optional,” and “not recommended” to indicate the desirability of specific diagnostics. Treatment recommendations were graded according to three levels of flexibility. 9,10 For treatments, the term “standard” is the least flexible of the three, a “guideline” is more flexible, and an “option” is the most flexible. Options can exist because of insufficient evidence or because patient preferences are divided. The grading of diagnostic and treatment recommendations is detailed in chapter 2 (www.auanet.org.) The 1994 AHCPR guideline defined an Index Patient (the specific type of patient to whom the recommendations applied) in recognition of the differences in decision making that depend upon patient circumstances. Similarly, these diagnostic and treatment guidelines pertain only to men over the age of 50 without significant risk (as ascertained by history) of non-BPH causes of LUTS. Men with polyuria, underlying neurologic disease, or prior lower urinary tract disease and younger men with voiding dysfunction will require more extensive evaluation. These important causes of voiding function are not specifically addressed in this guideline. DIAGNOSTIC EVALUATION OF BENIGN PROSTATIC HYPERPLASIA Upon review of the diagnostic recommendations in the 1994 AHCPR guideline, the Panel decided that an evidence-based update was not necessary. The Panel unanimously agreed that the prior recommendations and decision diagram for diagnosis were still valid and reflective of “best practice” with five exceptions, which were derived from the Panel’s expert opinion: • Serum prostate-specific antigen (PSA) measurement is recommended in select patients; • Urine cytology is recommended as an option in men with predominantly irritative symptoms; • Other validated symptom assessment instruments are supplementary to the AUA Symptom Score; • Serum creatinine measurement is no longer recommended on initial evaluation in the standard patient; and • Discussion of treatment options with the patient is recommended before pressure-flow testing is performed. The 1994 diagnostic guidelines, with italicized revisions, are revisited below using the previously referenced studies from that publication. An algorithm (figure 1.1) is provided as a framework for diagnosis and treatment and not as a rigid pathway that must be followed in all cases. Individual patients will present for whom deviations from these policies are appropriate. In such circumstances, the clinician should exercise clinical judgment and act in the patient’s best interest. Benign prostatic hyperplasia (BPH) diagnosis and treatment Initial evaluation. Lower urinary tract pathologies in aging men produce similar, if not identical, symptoms. Therefore, the challenge in patients with LUTS is to establish that the symptoms are due to BPH. Nonprostatic causes of symptoms can be excluded in a significant number of patients on the basis of a medical history, physical examination, and urinalysis. Recommended: In the initial evaluation of all patients presenting with LUTS suggestive of BPH: • A medical history should be taken to identify other causes of voiding dysfunction or comorbidities that may complicate treatment. The medical history should focus on the urinary tract, previous surgical procedures, and general health issues, specifically, medical conditions and symptoms that lead to bladder dysfunction or excessive urine production (polyuria), family history of prostate disease (BPH and cancer), and fitness for possible surgical procedures. Patient voiding diaries, where the frequency of micturition and urine volume is recorded, may be helpful in selected patients, especially in those with nocturia as the predominant symptom. • A physical examination, including both a digital rectal examination (DRE) and a focused neurologic examination, should be performed. The presence of locally advanced prostate cancer, which also can produce LUTS, should be excluded by DRE. Digital rectal exam tends to underestimate the true prostate size: if the prostate feels large by DRE, it usually also is found to be enlarged by ultrasound or other measurement techniques. 11,12 A focused neurologic examination should assess the patient’s general mental status, ambulatory status, lower extremity neuromuscular function, and anal sphincter tone. • A urinalysis should be performed by dipstick testing or microscopic examination of the sediment to screen for hematuria and urinary tract infection (UTI). Bladder cancer, carcinoma in situ of the bladder, UTIs, urethral strictures, distal urethral stones, and bladder stones can produce LUTS in aging men. Although hematuria or pyuria is not universally present in these conditions, a normal urine examination makes these diagnoses less likely. 13–16 • Measurement of the serum prostate-specific antigen (PSA) should be offered to the following patients: 1) those with at least a 10-year life expectancy and for whom knowledge of the presence of prostate cancer would change management; or 2) those for whom the PSA measurement may change the management of their voiding symptoms. Serum PSA is one predictor of the natural history of BPH—men with higher serum PSA levels have a higher risk of future growth of the prostate, symptom and flow rate deterioration, acute urinary retention, and BPH-related surgery. 17–19 This recommendation does not address the value of PSA screening in the testing of asymptomatic men in the general population. Rather, because prostate cancer is one of the potential causes of LUTS in aging men, PSA (together with DRE) is a relatively sensitive way to exclude prostate cancer as a diagnosis. 20–22 Physician and patient concern, however, lies with the specificity of the test—approximately 25% of men with BPH have a serum PSA greater than 4 ng/ml. Because of the overlap between serum PSA values in men with BPH and those with clinically localized prostate cancer, PSA velocity (PSAV), free/total PSA ratio, complexed PSA (cPSA), and PSA density (PSAD) measurements may help improve diagnostic specificity. 23,24 The benefits and risks of PSA testing should be discussed with the patient. In most patients, a normal DRE should be sufficient to exclude locally advanced cancer as a cause of voiding dysfunction. Prostate-specific antigen testing is most appropriate for patients likely to have a natural life span greater than 10 years and in whom the known presence of prostate cancer would change management or for whom the PSA measurement may change the management of the patient’s voiding symptoms. [This recommendation is based on the Panel’s expert opinion.] Optional: Urine cytology may be considered in men with a predominance of irritative symptoms, especially with a history of smoking or other risk factors, to aid in the diagnosis of bladder carcinoma in situ and bladder cancer. Not recommended: The routine measurement of serum creatinine levels is not indicated in the initial evaluation of men with LUTS secondary to BPH. Baseline renal insufficiency appears to be no more common in men with BPH than in men of the same age group in the general population. The Panel reviewed the experience in several large BPH clinical trial databases that have more than 10,000 patient-years of follow-up. Renal insufficiency has been reported in well under 1% of patients in these studies and is commonly secondary to non-BPH causes (e.g., diabetic nephropathy). Moreover, in the MTOPS trial (Medical Therapy of Prostatic Symptoms), 81 out of 4394 (1.8%) men screened for participation were excluded due to renal or hepatic impairment, defined as serum creatinine >2 mg/dl or significant liver enzyme abnormalities, respectively. No information is available regarding the number of patients whose renal insufficiency was due to BPH versus other causes; thus, the number of men presenting with renal insufficiency due to BPH is most likely also under 1%. If urinalysis and/or history and physical examination suggest underlying renal disease or urinary retention, measurement of serum creatinine also may be necessary prior to the performance of renal imaging studies that require intravenous contrast. [These recommendations are based on the Panel’s expert opinion.] Symptom assessment. Most patients who seek treatment for BPH do so because symptoms alter quality of life. Symptom quantification is therefore of major importance in determining the severity of disease, in documenting the response to therapy, and in detecting symptom progression in men managed by watchful waiting. The AUA Symptom Index (Appendix 1-A) or the identical IPSS is recommended for symptom assessment in each patient presenting with BPH because it is superior to an unstructured interview in quantifying symptom frequency and severity. Using seven questions that relate to associated symptoms, 1 classification ranges from mild (0 to 7) to moderate (8 to 19) to severe (20 to 35). 25,26 Some patients may require an explanation of the questions to adequately understand their intent. Although validated for its clarity, test/retest reliability, internal consistency, and criteria strength, this tool is not a replacement for personal discussion of symptoms with the patient. Recommended: The AUA Symptom Index (identical to the seven symptom questions of the International Prostate Symptom Score [IPSS]) should be used as the symptom-scoring instrument in the initial assessment of each patient presenting with BPH. Symptom score changes and the degree of each patient’s bother due to the symptoms should be the primary determinants of treatment response or disease progression in the follow-up period. However, symptom scores alone do not delineate the morbidity of a prostate problem as perceived by the individual patient. An intervention may be more logical for a moderately symptomatic patient who finds his symptoms bothersome than for a severely symptomatic patient who finds his symptoms tolerable. Optional: Other validated assessment instruments addressing the frequency or severity of LUTS in men with BPH, bother due to symptoms, interference with daily activities, urinary continence, sexual functioning and health-related general or disease-specific quality of life may be administered. Examples of these instruments are the International Continence Society male questionnaire 27 and the Danish Prostatic Symptom Score, 28 which measure symptom severity and frequency; the BPH Impact Index (Appendix 1-B), 3 which measures the impact of symptoms on activities of daily living and their level of interference; and the Disease Specific Quality of Life (QoL) question of the IPSS (Appendix 1-A), which measures quality of life as it is impacted and impaired by BPH. Baseline sexual function, treatment choices, and/or impact of treatment is measured by sexual function questionnaires. [These recommendations are based on Panel expert opinion.] Optional diagnostic tests. Optional tests are those that are not required but may aid in the decision-making process. When the initial evaluation suggests a nonprostatic cause for the patient’s symptoms or when the patient selects invasive therapy, the physician may consider additional diagnostic testing if the results of the test(s) are likely to change the patient’s management or more precisely predict the benefits and risks of the selected treatment. The 1994 AHCPR guideline suggested that the physician consider performing one or more “optional” diagnostic tests prior to offering treatment options to the patient. 29 In some cases, additional diagnostic tests may aid in the selection of an invasive treatment that is best for an individual patient (e.g., identification of prostate middle lobe). The 2001 5th International Consultation on BPH, co-sponsored by the World Health Organization, also deemed flow rate and post-void residual urine (PVR) volume to be optional tests for men who were considering therapy for bothersome LUTS. Optional: Following the initial evaluation of the patient, urinary flow-rate recording and measurement of post-void residual urine (PVR) may be appropriate. These tests usually are not necessary prior to the institution of watchful waiting or medical therapy. However, they may be helpful in patients with a complex medical history (e.g., neurologic or other diseases known to affect bladder function or prior failure of BPH therapy) and in those desiring invasive therapy. Urinary flow-rate recording (uroflowmetry), specifically Qmax, may predict the response to surgery and, to a lesser degree, the natural history of the disease. Men with LUTS and normal Qmax are more likely to have a non-BPH-related cause of their symptoms. Nevertheless, the symptom response to many therapies, specifically alpha blockers, is not dependent upon baseline flow rate. Men with Qmax less than 10 ml/sec are more likely to have urodynamic obstruction and are therefore more likely to improve with surgery. Men with normal flow rates but significant urinary symptoms are more likely to have nonprostatic causes for those symptoms requiring more extensive investigation. Urinary flow rate, though, predicts less well the response to medical therapy or the failure of watchful waiting. Because of test-retest variability and a lack of appropriately designed outcome studies, it is not feasible to establish a flow-rate “cut-point” for decision making. Large PVR volumes (e.g., 350 ml) may indicate bladder dysfunction and predict a slightly less favorable response to treatment. In addition, large PVRs may herald progression of disease. Still, residual urine is not a contraindication to watchful waiting or medical therapy. Because of large test-retest variability and a lack of appropriately designed outcome studies, it is not feasible to establish a PVR “cut-point” for decision making. The Panel considered the use of PVR measurements optional in men undergoing noninvasive therapy based on the observation that the safety of noninvasive therapy has not been documented in patients with residual urine (200 to 300 ml). In some studies, however, residual urine has predicted a high failure rate of watchful waiting. 30 Within the range of residual urine values from 0 to 300 ml, the PVR does not predict the response to medical therapy. Although long-term, controlled data are lacking, many patients maintain fairly large amounts of residual urine without evidence of UTI, renal insufficiency, or bothersome symptoms. Therefore, no level of residual urine, in and of itself, mandates invasive therapy. INITIAL MANAGEMENT AND DISCUSSION OF TREATMENT OPTIONS WITH THE PATIENTS Management of patients with mild symptoms or moderate to severe symptoms without bother. From the initial evaluation, the physician should determine whether the patient has developed a serious complication of BPH that would direct treatment toward surgical options. Patients with only mild symptoms or moderate to severe symptoms that are not bothersome generally will not benefit from therapy because these symptoms do not significantly impact quality of life. 25,26,31 In addition, the risks of medical therapy outweigh the benefits of symptom improvement in this group of men. Therefore, the Panel felt that the recommendation, from the 1994 AHCPR guideline, was still appropriate with one modification, which is the inclusion of men with “nonbothersome” symptoms in the “mild” category. Men who have moderate to severe symptom frequency and severity but are not bothered by their symptoms should not be considered for further diagnostic tests or active treatment. Standard: Patients with mild symptoms of BPH (AUA Symptom Score ≤7) and patients with moderate or severe symptoms (AUA Symptom Score ≥8) who are not bothered by their symptoms (i.e., they do not interfere with the daily activities of living) should be managed using a strategy of watchful waiting. Management of patients with bothersome moderate to severe symptoms. The degree to which BPH patients are bothered by LUTS varies among individual patients with the same level of symptoms, although in general the level of bother and interference will increase with the level of symptom severity. 32 Although patients with mild symptoms or mild to severe symptoms that are not bothersome prefer watchful waiting, there is a wide range of preference in patients with bothersome moderate to severe symptoms. 29 Therefore, the “best” treatment from the patient’s viewpoint may differ from that believed by the physician to be the most efficacious treatment. Patients may prefer less effective therapy if it also has less risk or cost. Treatment options—watchful waiting and medical, minimally invasive or surgical therapies—are defined in table 1.1, and information on their harms and benefits is presented in the Simplified Outcomes Tables (Appendix 1-C). Table 1.1. Treatment options for patients with moderate to severe symptoms of benign prostatic hyperplasia Watchful Waiting Medical Therapies Alpha-adrenergic blockers Alfuzosin Doxazosin Tamsulosin Terazosin 5 Alpha-reductase inhibitors Dutasteride* Finasteride Combination therapy (alpha blocker and 5 alpha-reductase inhibitor)*,† Minimally Invasive Therapies Transurethral microwave heat treatments CoreTherm™* Prostatron® (various versions) Targis® TherMatrx™* Transurethral needle ablation UroLume stent®‡ Surgical Therapies Transurethral resection of the prostate Transurethral electrovaporization Transurethral incision of the prostate Transurethral holmium laser resection/enucleation Transurethral laser vaporization Transurethral laser coagulation (e.g., visual laser ablation) Open prostatectomy * Recommendations based on randomized, controlled trials not included in the outcomes tables. † The Panel assumes that the combination of any effective alpha blocker and 5 alpha-reductase inhibitor probably produces a comparable benefit. However, the best-tested combination is doxazosin and finasteride. The safety of specific combinations other than finasteride plus doxazosin, terazosin, and alfuzosin has not been assessed. ‡ Recommended for a subset of patients, see text. Option: Treatment options for patients with bothersome moderate to severe symptoms of BPH (AUA Symptom Score ≥8) include watchful waiting and the medical, minimally invasive, or surgical therapies defined intable 1.1. Guideline: Information on the benefits and harms of the BPH treatment options (including watchful waiting) should be explained to patients with moderate to severe symptoms (AUA Symptom Score ≥8) who are bothered enough to consider therapy. At this point, the benefits and risks of all therapeutic interventions should be discussed with the patient using the Simplified Outcomes Tables presented in Appendix 1-C. It is appropriate for patients with moderate symptoms and bother to choose watchful waiting if they feel that the benefits outweigh the risks of an active therapy. Patients choosing medical therapies may be prescribed the most appropriate agent(s) at this time without additional testing. Patients choosing invasive therapies may benefit from additional optional diagnostic tests. Optional diagnostic tests for patients who choose invasive therapy. Determining the relative significance of performing certain diagnostic tests prior to treatment initiation has been a complex task. In the BPH clin