Update on the American Urological Association Guidelines for the Treatment of Benign Prostatic Hyperplasia

Advances in Alpha-Blocker Therapy in the Management of Urological Disorders

RIUS0002(Sanofi)_12-05.qxd 12/5/06 6:15 PM Page S10 ALPHA-BLOCKER THERAPY FOR UROLOGICAL DISORDERS Update on the American Urological Association Guidelines for the Treatment of Benign Prostatic Hyperplasia Steven A. Kaplan, MD Institute of Bladder and Prostate Health, Weill Medical College, Cornell University, New York, NY The updated 2003 American Urological Association (AUA) Guidelines for the treatment of benign prostatic hyperplasia (BPH) are the culmination of an exhaustive effort predicated on scientifically accepted methods of reviewing the medical literature. In this second publication of the guidelines, a multidisciplinary panel reviewed a new meta-analysis of outcome data from the BPH literature from before and after 1994. The major differences between the 2 guidelines are the changes in our understanding of the biology of the prostate and the introduction of new therapies. The vast majority of randomized controlled trials, particularly with respect to minimally invasive therapies and progression of BPH, were performed after the release of the 1994 guidelines. Also, the most recent AUA panel carefully reviewed unpublished data to make the guidelines as timely as possible. Studies that were subsequently published included those on the value of combination medical therapy for BPH. The panel agreed on updated recommendations for the treatment of moderate-to-severe lower urinary tract symptoms associated with BPH, and diagnostic algorithms were revised. The durability and utility of the present guidelines should exceed that of its predecessor. [Rev Urol. 2006;8(suppl 4):S10-S17] © 2006 MedReviews, LLC Key words: AUA Guidelines • Benign prostatic hyperplasia • Lower urinary tract symptoms • 5
-reductase inhibitors • Combination therapy • AUA Symptom Scores vidence-based medicine has become the credo of clinically based medicine over the past few years. Ultimately, being able to gather, assimilate, and then utilize the best available data should lead to improved health care delivery to our patients. A more uniform and homogenous approach to various E S10 VOL. 8 SUPPL. 4 2006 REVIEWS IN UROLOGY RIUS0002(Sanofi)_12-05.qxd 12/5/06 6:15 PM Page S11 Update on AUA BPH Treatment Guidelines health care issues should in theory lead to better outcomes. The use of evidence-based guidelines is not unique to urology or to the management of benign prostatic hyperplasia (BPH). In the 1990s, under the aegis of the Agency for Health Care Policy and Research, the Benign Prostatic Hyperplasia Guidelines Panel published recommendations on the diagnosis and treatment of BPH.1 A multidisciplinary, 13-member, private-sector panel based the guidelines on a review of available literature (1200 abstracts and 200 articles) on BPH. The thrust of the guide- Over the past decade, numerous new medical, minimally invasive, and surgical therapies for BPH have been described. In fact, most of our current knowledge of therapies for BPH are based on various open-label studies and randomized clinical trials performed in the 1990s. These include landmark medical studies, such as the Veterans Affairs Cooperative Study, the Proscar Long-Term Efficacy and Safety Study (PLESS), the Prospective European Doxazosin and Combination Therapy (PREDICT) Study, and the Medical Therapy of Prostatic The AUA Guidelines Committee sought input from numerous sources, including internists, surgeons, family physicians, and urologists, during the process of updating the 1994 guidelines. lines were recommendations that patients consult with physicians and decide on a treatment on the basis of likely treatment outcomes.2,3 In 2004, the European Association of Urology (EAU) published the first update on the assessment, therapy, and follow-up of men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction.4 Part of the difficulty in assessing clinical practice guidelines is the variability in terminology, assessment, and treatment. For example, the American Urological Association (AUA) Guidelines refer to BPH, whereas the EAU Guidelines refer to benign prostatic obstruction. Moreover, differences in methodology and rigor of development invariably lead to differences in recommendations.5,6 This applies to both the number and type of diagnostic tests recommended, as well as to therapeutic recommendations. Striking a balance between up-to-date research and completeness versus user-friendly guidelines is challenging. Nevertheless, clinical practice guidelines provide a framework for discussion and should be used in the context of overall health care delivery. Symptoms (MTOPS) Study.7-9 Moreover, the use of minimally invasive therapies, such as transurethral microwave thermotherapy (TUMT), transurethral needle ablation (TUNA) of the prostate, and interstitial laser coagulation of the prostate, had their renaissance during the last decade. Finally, modifications of the most common surgical procedure to treat BPH, transurethral resection of the prostate (TURP), using electrovaporization and the holmium laser, were predicated on scientifically accepted methods of reviewing the medical literature. Moreover, the use of a metaanalysis of all available outcome data formed the basis of the document. An important role of the members of the panel was to fill in the gaps. In other words, where there was little evidencebased medicine or conflicting information, the consensus judgment of the panel members was used to support the recommendations. Recommendation terms that quickly became part of the urologic vernacular included standards, which must be done in all cases; guidelines, which should be done in most cases; and options, which may be done, albeit with no clear evidence of clinical utility (Figure 1).12 A major breakthrough of the guidelines has been that urologists became well aware of the notion of describing risks and benefits of various treatment algorithms with their patients before making treatment decisions.13 This is particularly relevant in qualityof-life disorders, such as LUTS secondary to BPH, urinary incontinence, and sexual dysfunction. Evolving ways of thinking of BPH developed as well. In particular, the importance of BPH progression—how to define it, follow it, and treat it— became the mainstay of both epi- The vast majority of randomized controlled trials, particularly with respect to minimally invasive therapies and progression of benign prostatic hyperplasia, were performed after the release of the 1994 guidelines. unknown at the time of the first iteration of the AUA Guidelines.10,11 Therefore, the AUA Guidelines Committee reconvened a panel to update these guidelines. The committee sought input from numerous sources, including internists, surgeons, family physicians, and urologists during this process. Both sets of guidelines were the culmination of an exhaustive effort demiologic and medical therapy studies in the 1990s. In the second iteration of the guidelines, the multidisciplinary panel reviewed a new meta-analysis of outcome data from the BPH literature from before and after 1994. The vast majority of randomized controlled trials, particularly with respect to minimally invasive therapies and progression of BPH, were performed after the VOL. 8 SUPPL. 4 2006 REVIEWS IN UROLOGY S11 RIUS0002(Sanofi)_12-05.qxd 12/5/06 6:15 PM Page S12 Update on AUA BPH Treatment Guidelines continued Initial Evaluation • History • DRE & Focused PE • Urinalysis* • PSA in Select Patients† Presence of • Refractory Retention or Any of the Following Clearly Related to BPH • Persistent Gross Hematuria‡ AUA/IPSS Symptom Index Assessment of Patient Bother Mild Symptoms (AUA/IPSS ⱕ 7) or No Bothersome Symptoms • Bladder Stones‡ • Recurrent UTIs‡ • Renal Insufficiency Moderate/Severe Symptoms (AUA/IPSS ⱖ 8) Optional Diagnostic Tests • Uroflow • PVR Surgery Discussion of Treatment Options Patient Chooses Noninvasive Therapy Patient Chooses Invasive Therapy Optional Diagnostic Tests§ • Pressure Flow • Urethrocystoscopy • Prostate Ultrasound Watchful Waiting Medical Therapy Minimally Invasive Therapies Surgery Figure 1. Algorithm for benign prostate hyperplasia (BPH) diagnosis and treatment. DRE, digital rectal examination; PE, physical examination; PSA, prostate-specific antigen; AUA, American Urological Association; IPSS, International Prostate Symptom Score; UTI, urinary tract infection; PVR, postvoid residual urine. *A course of a 5
-reductase inhibitor may be used in patients with clinically significant prostatic bleeding. If bleeding persists, tissue-ablative surgery is indicated. †Patients with at least a 10-year life expectancy for whom knowledge of the presence of prostate cancer would change management or patients for whom the PSA measurement may change the management of voiding symptoms. ‡Surgery chosen after exhausting other therapeutic options as discussed in detail in the text. §Some diagnostic tests are used in predicting response to therapy. Pressure-flow studies are most useful in men before surgery. Reprinted with permission from the AUA Practice Guidelines Committee.12 release of the 1994 guidelines. Also, the panel carefully reviewed unpublished data to make the guidelines as timely as possible. Specifically, raw data were analyzed by an AUAcontracted statistician, discussed ex- S12 VOL. 8 SUPPL. 4 2006 tensively by the panel, and incorporated into the guidelines. Studies that were subsequently published included those on the value of combination medical therapy for BPH, such as PREDICT and MTOPS.8,9,14 REVIEWS IN UROLOGY The panel agreed on updated recommendations for the treatment of LUTS and BPH. Moreover, diagnostic algorithms were updated. The following represents highlights of both the updated diagnostic and therapeutic RIUS0002(Sanofi)_12-05.qxd 12/5/06 6:15 PM Page S13 Update on AUA BPH Treatment Guidelines algorithms, and how these recommendations regarding the evaluation and treatment of BPH have evolved since 1994. In addition, differences between the AUA and EAU Guidelines will be highlighted. Diagnostic Recommendations The major differences between the 2 published guidelines are the changes in our understanding of the biology of the prostate and the introduction of new therapies. The AUA Practice Guidelines Committee recommends a urinalysis, testing of serum prostatespecific antigen (PSA) levels, and completion of a validated symptom index in the initial evaluation. Serum PSA determination is recommended for men with more than a 10-year life expectancy and for those for whom PSA levels may influence BPH treatment. This includes most patients who are considering treatment with a 5
-reductase inhibitor. Serum PSA is a useful surrogate marker for prostate size and can also be used to predict future prostate growth, as well as the risk for urinary retention or surgery.15-17 Measurement of serum creatinine is no longer routinely recommended because multiple long-term, placebocontrolled trials have shown that the incidence of renal insufficiency in men with BPH is the same as in the general population. The EAU panel recommends the measurement of serum creatinine at the initial evaluation. In addition, uroflowmetry (with a voided volume of  150 mL) and measurement of a postvoid residual (PVR) urine volume are recommended tests. Large PVR urine volumes ( 200 mL) may indicate bladder dysfunction. The AUA Symptom Index (identical to the 7 symptom questions of the International Prostate Symptom Score) should be used as the symptom-scoring instrument in the initial assessment of each patient presenting with BPH.18-21 The AUA Symptom Scores (AUA-SS) of 0 to 7 are classified as mild, 8 to 19 as moderate, and 20 to 35 as severe LUTS. It is suggested that patients with mild symptoms of BPH (AUA-SS  7) and patients with moderate or severe symptoms (AUASS  8) who are not bothered by their symptoms (ie, they do not interfere with the daily activities of living) should be managed using a strategy of watchful waiting. Although patients with 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. In general, most patients undergo medical management before any form of surgical intervention, whether TURP, transurethral incision of the prostate, open prostatectomy, or minimally invasive therapies such as heat therapies for the prostate (most commonly TUMT, TUNA by radiofrequency energy, and waterinduced thermotherapy). When counseled as to treatment options and their potential complications, most patients prefer less invasive treatments. In fact, almost 85% of men with BPH treated medically are pleased with their choice when surveyed 1 year after treatment commencement. In 2004, these different classes of medicines included phytotherapy,
-blockers, and 5
reductase inhibitors. Another major change since 1994 is the indications for surgical intervention. In the past, patients with gross hematuria were routinely treated by surgery. Today, they are offered a 5
reductase inhibitor such as finasteride or dutasteride.22 Urinary retention is treated with the concomitant use of an indwelling catheter and an
blocker such as alfuzosin or tamsulosin. A trial without the use of a catheter is then instituted. Therapeutic Recommendations The panel has chosen a number of recommended treatment options for patients with modest-to-severe and bothersome LUTS associated with BPH (Table 1).23 Watchful Waiting A significant proportion of men with LUTS will not elect medical or surgical intervention. Reasons include nonbothersome symptoms, the perception that the complications of treatment are greater than the inconveniences of the symptoms, and/or the reluctance to take a daily pill because of unrecognized long-term side effects and the cost of treatment. In addition, the progression of BPH is generally slow and unpredictable, and not all patients experience worsening of symptoms, even if objective measurements such as peak flow rates continue to decline. Watchful waiting does not imply total absence of intervention. Severity and bother due to LUTS may be improved by decreasing total fluid intake, moderating the intake of alcohol- and caffeine-containing products, limiting the use of salt and spices, and maintaining timed voiding schedules.13,18,20-22 The impact of watchful waiting was examined in a study of 556 men randomized to either surgery or watchful waiting.24 There were twice as many treatment failures in the watchful waiting group. Of the patients in the watchful waiting group, 24% underwent surgery during the 3-year study period, with one third of surgeries due to persistent symptoms. Patients stratified by preoperative symptom score revealed that those with low-tomoderate symptom scores in the watchful waiting group underwent TURP less frequently than those with high preoperative symptom scores. Phytotherapy Phytotherapies for BPH are becoming increasingly popular, and although VOL. 8 SUPPL. 4 2006 REVIEWS IN UROLOGY S13 RIUS0002(Sanofi)_12-05.qxd 12/5/06 6:15 PM Page S14 Update on AUA BPH Treatment Guidelines continued Table 1 Recommended Treatment Options for Patients With Modest-toSevere and Bothersome Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia Watchful Waiting Medical Therapies Alpha-adrenergic blockers Alfuzosin Doxazosin Tamsulosin Terazosin 5
-reductase inhibitors Dutasteride* Finasteride Combination therapy (
-blocker and 5
-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 (eg, visual laser ablation) Open prostatectomy Data from the American Urological Association.23 *Recommendations based on randomized, controlled trials not included in the outcomes tables. † The panel assumes that the combination of any effective
-blocker and 5
-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). many physicians remain skeptical of their value, patients generally seem satisfied with their utility. Two of the more common herbal medications used include Serenoa repens (saw palmetto berry) and Pygeum africanum (red stinkwood or African plum). A meta-analysis of randomized trials using saw palmetto showed that in the short term (average duration  9 weeks), improvements in symptoms (AUA-SS  1.4) and flow rates (1.93 mL/s) approached those of finasteride.25,26 Constituents include flavonoids, -sitosterol, campesterol, and stigmasterol. These ingredients have been shown to reduce swelling and inflammation and seem to naturally inhibit both type 1 and type 2 5
-reductase, as well as block dihydrotestosterone from binding to cytosolic androgen receptors in the prostate gland. The latest meta-analysis of clinical trials using saw palmetto, conducted by Boyle and colleagues, included only those studies using Permixon (Pierre Fabre Médicament, Castres, France), a standardized lipid-sterolic extract of Serenoa repens.27 All of the published trials together involved 2859 patients studied for 21 to 180 days. The estimated effect of Permixon was an increase of 2.71 mL/s in peak urinary flow rates, compared with 0.51 mL/s for placebo. In addition, Permixon decreased nocturnal urinations by 1.19, compared with 0.69 for placebo. Treatment duration did not influence the magnitude of either of these events. The EAU panel recommended that further studies meeting the criteria of the World Health Organization BPH Conference (12-month duration, randomized, placebo-controlled) are required before plant extracts can be recommended for the treatment of LUTS. Alpha-Adrenoceptor Antagonists There are currently 4
-blockers that S14 VOL. 8 SUPPL. 4 2006 REVIEWS IN UROLOGY are US Food and Drug Administration (FDA) approved to treat LUTS: doxazosin, terazosin, tamsulosin, and alfuzosin.28-35 The AUA Guidelines Committee believes that all 4 are equally effective, causing on average a 4- to 6-point improvement in the AUA-SS, which most patients perceive as a meaningful change. Adverse side effects commonly reported with different
1-blockers include dizziness, headache, asthenia, postural hypotension, rhinitis, and sexual dysfunction, most commonly occurring in approximately 5% to 9% of patient populations. 5-Alpha-Reductase Inhibitors PLESS was the largest clinical trial to investigate finasteride for the management of BPH.15-17 In this multicenter, double-blind, placebocontrolled study conducted in the United States, more than 3000 men with moderate-to-severe urinary symptoms and an enlarged prostate at baseline were randomized to finasteride 5 mg/d or placebo. During the 4-year study period, 152 (10%) of the 1516 men in the placebo group and 69 (5%) of the 1524 men in the finasteride group underwent surgery for BPH (reduction in risk with finasteride: 55%). Acute urinary retention developed in 99 men (7%) in the placebo group and 42 (3%) in the finasteride group (reduction in risk: 57%). Among men who completed the study, mean decreases in symptom scores were 3.3 in the finasteride group and 1.3 in the placebo group (P  .001). Treatment with finasteride improved urinary flow rates and reduced prostate volume (P  .001). This study suggested that long-term medical therapy could impact the natural history of BPH as manifested by acute urinary retention and surgery. Moreover, the degree of symptomatic improvement in those who responded seemed to RIUS0002(Sanofi)_12-05.qxd 12/5/06 6:15 PM Page S15 Update on AUA BPH Treatment Guidelines be equal to that of patients taking
blockade. Investigators have hypothesized that inhibition of both types 1 and 2 5
-reductase may demonstrate increased efficacy in the treatment of BPH.36,37 Dutasteride is a second-generation 5
-reductase inhibitor that inhibits both types 1 and 2 5
-reductase. Dutasteride was investigated in 3 large, well-controlled, multicenter studies involving 4325 men 50 years of age or older. Data from these 2-year clinical trials demonstrated that treatment with 0.5 mg dutasteride once daily reduced the risk of acute urinary retention and BPH, improved BPH-related symptoms, decreased prostate volume, and increased maximum urinary flow rates compared with placebo. Finasteride and dutasteride suppress dihydrotestosterone production by 70% and 93%, respectively, although their objective and subjective effects are similar. Both agents improve voiding symptoms, reduce the incidence of urinary retention, and decrease the likelihood of surgery for BPH. These agents may not work for all men and may take several months before activity is noted. However, for those in whom they are effective, the impact may be profound. Combination Therapy The initial experience with
-blocker and 5
-reductase inhibitor combination therapy was not promising. In a Veterans Affairs Cooperative Group Study,7 1 year of combination therapy was no more effective than monotherapy in improving symptoms or flow rates and substantially increased the cost of treatment. The recently published MTOPS study has changed our thinking regarding combination therapy. More than 3000 men were randomized to receive either placebo, doxazosin (
-blocker), finasteride (5
-reductase inhibitor), or combination therapy.8,9 The principal outcome followed was clinical progression, defined as either an increase of at least 4 points in the AUA-SS, or urinary retention, incontinence, renal insufficiency, or recurrent urinary tract infection. Other dependent variables included maximal urinary flow rate, serum PSA, and incidence of invasive therapy. After a low energy (TherMatrx); 2 of these devices feature water cooling (Targis and Prostatron); and 1 of them uses an intraprostatic needle to report temperature within the prostate and thereby individualizes the treatment (CoreTherm). Despite these differences, the panel came to the conclusion that there is no superiority of a particular TUMT treatment over another. The FDA noted that a number of patients treated by cooled ther- The AUA panel came to the conclusion that there is no superiority of 1 transurethral microwave heat treatment over the other. median 4.5 years of follow-up, median changes in AUA-SS were 4 for placebo, 6 for doxazosin, 5 for finasteride, and 7 for combination therapy. All differences were statistically significant. Clinical progression, which was mostly due to increasing AUA-SS, occurred in 4.5 per 100 patients per year in the placebo group. Doxazosin and finasteride reduced the risk of progression by 39% and 34%, respectively. Although these reductions were significantly different from those with placebo, the difference between the 2 agents was not significant. Combination therapy caused a 66% risk reduction of clinical progression compared with placebo, and this was significantly different from the other 3 arms. Minimally Invasive Therapies Of the minimally invasive therapies, the panel recommends 4 transurethral microwave heat treatments as options: CoreTherm® (ProstaLund Operations, Lund, Sweden), the Prostatron® device (Urologix Inc., Minneapolis, MN) in different software versions, the Targis® system (Urologix Inc., Minneapolis, MN), and the TherMatrx® device (American Medical Systems, Minnetonka, MN). Three of these devices are high energy, and 1 device is motherapy had significant complications, including fistula and penile necrosis. This underscores the need for physicians to be in attendance when these treatments are administered. Other minimally invasive therapies recommended as treatment options are TUNA by radiofrequency energy and the UroLume® stent (American Medical Systems) as the only mechanical device to maintain patency of the prostatic urethra. The stent, however, is not recommended for typical patients but only for patients at poor surgical risk. Therapies such as injection of absolute ethanol into the prostate, highintensity focused ultrasound, and certain other transurethral heat-based therapies (interstitial laser coagulation, water-induced thermotherapy), and the Plasma Kinetic™ Tissue Management System (Gyrus Medical Ltd., Cardiff, United Kingdom) are listed as emerging therapies. Other therapies are formally recommended as treatment options. These include laser therapies to either resect or vaporize the prostate, such as TURP using the holmium laser. Conclusions The updated AUA Guidelines made few changes to the diagnostic algorithm of VOL. 8 SUPPL. 4 2006 REVIEWS IN UROLOGY S15 RIUS0002(Sanofi)_12-05.qxd 12/5/06 6:15 PM Page S16 Update on AUA BPH Treatment Guidelines continued BPH. Using a meta-analysis and extensive review of the published and unpublished raw data sets, new therapeutic recommendations were made. The durability and utility of the 2003 updated AUA Guidelines for BPH should be longer than those of its predecessor. New research is underway on the biology of prostate disease and the use of novel therapeutic agents, but it is unclear what impact and roles these agents will have over the next 5 years. However, emerging medical therapies such as anticholinergics, phosphodiesterase type 5 inhibitors, 3 agonists, and phytotherapeutic agents, as well as the current National Institutes of Health trials involving botulinum toxin A, will give us greater insight into the management of male LUTS. 2. 3. 4. 5. 6. 7. References 1. McConnell JD, Barry MJ, Bruskewitz RC, et al. Clinical Practice Guideline Number 8: Benign Prostatic Hyperplasia: Diagnosis and Treatment. AHCPR publication no. 94-0582. Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, US Dept of Health and Human Services; 1994. 8. McConnell JD, Barry MJ, Bruskewitz RC, et al. Benign Prostatic Hyperplasia: Diagnosis and Treatment. Quick Reference Guide for Clinicians. AHCPR publication no. 95-0583. Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, US Dept of Health and Human Services; 1994. McConnell JD, Barry MJ, Bruskewitz RC, et al. Treating Your Enlarged Prostate. Patient Guide. AHCPR publication no. 94-0584. Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, US Dept of Health and Human Services; 1994. Madersbacher S, Alivizatos J, Rioja Sanz C, et al. EAU 2004 guidelines on assessment, therapy and follow-up of men with lower urinary tract symptoms suggestive of benign prostatic obstruction (BPH Guidelines). Eur Urol. 2004;46:547-554. Irani J, Brown CT, van der Meulen J, Emberton M. A review of guidelines on benign prostatic hyperplasia and lower urinary tract symptoms: are all guidelines the same? BJU Int. 2003; 92:937-942. Roehrborn CG, Bartsch G, Kirby R, et al. Guidelines for the diagnosis and treatment of benign prostatic hyperplasia: a comparative international overview. Urology. 2001;58:642-650. Lepor H, Williford WO, Barry MJ, et al. The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. N Engl J Med. 1996;335:533-539. McConnell J, Roehrborn C, Bautista O, et al. The long-term effects of doxazosin, finasteride and the combination on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;349:2387-2398. 9. 10. 11. 12. 13. 14. 15. 16. Vaughan ED Jr, Lepor H. Medical Management of BPH. AUA Update Series 1996. Volume 15, Lessons 3-4. Linthicum, MD: American Urological Association. Littlejohn JO Jr, Ghafar MA, Kang YM, Kaplan SA. Transurethral resection of the prostate: the new old standard. Curr Opin Urol. 2002;12:19-23. Mebust WK, Holtgrewe HL, Cockett ATK, Peters PC. Transurethral prostatectomy: immediate and postoperative complications. A cooperative study of 13 participating institutions evaluating 3885 patients. J Urol. 1989;141:243-247. AUA Practice Guidelines Committee. AUA guideline on management of benign prostatic hyperplasia (2003), chapter 1: diagnosis and treatment recommendations. J Urol. 2003;170(2 pt 1):530547. Barry MJ, Cockett AT, Holtgrewe HL, et al. Relationship of symptoms of prostatism to commonly used physiological and anatomical measures of the severity of benign prostatic hyperplasia. J Urol. 1993:150(2 pt 1):351-358. Kirby RS, Roehrborn C, Boyle P, et al. Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial. Urology. 2003;61: 119-126. Roehrborn CG, Boyle P, Bergner D, et al. Serum prostate-specific antigen and prostate volume predict long-term outcome in symptoms and flow rate: results of a 4-year, randomized trial comparing finasteride vs placebo. PLESS Study Group. Urology. 1999;54:662-669. Roehrborn CG, McConnell J, Lieber M, et al. Serum prostate-specific antigen concentration is Main Points • Part of the difficulty in assessing clinical practice guidelines is the differences in methodology and rigor of development that can lead to varying recommendations (eg, several recommendations of the European Association of Urology Guidelines differ from those of the American Urological Association [AUA] Guidelines). Nevertheless, clinical practice guidelines provide a framework for discussion and should be used in the context of overall health care delivery. • Over the past decade, numerous new medical, minimally invasive, and surgical therapies for benign prostatic hyperplasia (BPH) have been described. In 2003, the AUA Guidelines Committee reconvened a panel to update the AUA Guidelines for the treatment of BPH, using a new meta-analysis of outcome data of the BPH literature from before and after 1994 as the basis of the document. • The major differences between the 2 published AUA Guidelines are the changes in our understanding of the biology of the prostate and the introduction of new therapies for the treatment of lower urinary tract symptoms (LUTS) and BPH, as well as the introduction of updated diagnostic algorithms. • The recent AUA Guidelines Committee recommends urinalysis, evaluation of serum prostate-specific antigen levels, and completion of a validated symptom index during the patient’s initial evaluation. • A major change since 1994 is the indications for surgical intervention. In the past, patients with gross hematuria were routinely treated by surgery; however, today they are offered a 5
-reductase inhibitor such as finasteride or dutasteride. • Recommended treatment options for patients with modest-to-severe and bothersome LUTS associated with BPH include watchful waiting, phytotherapy, treatment with
-adrenoceptor antagonists, combination therapy of
-blockers and 5
-reductase inhibitors, and minimally invasive therapies such as transurethral microwave thermotherapy. • The durability and utility of the 2003 updated AUA Guidelines for the treatment of BPH should exceed that of the earlier guidelines. S16 VOL. 8 SUPPL. 4 2006 REVIEWS IN UROLOGY RIUS0002(Sanofi)_12-05.qxd 12/5/06 6:15 PM Page S17 Update on AUA BPH Treatment Guidelines 17. 18. 19. 20. 21. a powerful predictor of acute urinary retention and need for surgery in men with clinical benign prostatic hyperplasia. Urology. 1999;53:473-480. Roehrborn CG, McConnell J, Bonilla J, et al. Serum PSA concentration is a strong predictor of future prostate growth in men with benign prostatic hyperplasia. J Urol. 2000;163:13-20. Denis L, McConnell JD, Yoshida O, et al. Recommendations of the International Scientific Committee: the evaluation and treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction. In: Denis L, Griffiths K, Shoury S, et al, eds. 4th International Consultation on Benign Prostatic Hyperplasia (BPH). Plymouth, England: Health Publication Ltd; 1997:669-684. Fowler FJ Jr, Wennberg JE, Timothy RP, et al. Symptom status and quality of life following prostatectomy. JAMA. 1988;259:3018-3022. Chatelain C, Denis L, Foo K, et al. Recommendations of the International Scientific Committee. In: 5th International Consultation on Benign Prostatic Hyperplasia (BPH). Plymouth, England: Health Publication Ltd; 2001:519-534. Chute CG, Panser LA, Girman CJ, et al. The prevalence of prostatism: a population-based survey of urinary symptoms. J Urol. 1993; 150:85-91. 22. 23. 24. 25. 26. 27. 28. Roehrborn CG, Boyle P, Nickel JC, et al. Efficacy and safety of a dual inhibitor of 5-alphareductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology. 2002;60: 434-441. The American Urological Association. Clinical guidelines. Available at: http//www.auanet.org/ guidelines/bph.cfm. Accessed October 10, 2006. Wasson JH, Reda DJ, Bruskewitz RC, et al. A comparison of transurethral surgery with watchful waiting for moderate symptoms of benign prostatic hyperplasia. The Veterans Affairs Cooperative Study Group on Transurethral Resection of the Prostate. N Engl J Med. 1995;332:75-79. Plosker GL, Brogden RN. Serenoa repens (Permixon). A review of its pharmacology and therapeutic efficacy in benign prostatic hyperplasia. Drugs Aging. 1996;9:379-395. Wilt TJ, Ishani A, Stark G, et al. Saw palmetto extracts for treatment of benign prostate hyperplasia: a systematic review. JAMA. 1998;280:16041609. Boyle P, Robertson C, Lowe F, et al. Metaanalysis of clinical trials of Permixon in the treatment of symptomatic benign prostate hyperplasia. Urology. 2000;55:533-539. Andersson KE. Alpha-adrenoceptors and benign prostatic hyperplasia: basic principles for treat- 29. 30. 31. 32. 33. 34. 35. 36. 37. ment with alpha-adrenoceptor antagonists. World J Urol. 2002;19:390-394. Kaplan SA, Kaplan NM. Alpha-blockade: monotherapy for hypertension and benign prostatic hyperplasia. Urology. 1996;48:541-550. Martin DJ. Preclinical pharmacology of
1adrenoceptor antagonists. Eur Urol. 1999;36 (suppl 1):35-41. Michel MC, Flannery MT, Narayan P. Worldwide experience with alfuzosin and tamsulosin. Urology. 2001;58:508-516. Narayan P, Tewari A. Overview of alpha-blocker therapy for benign prostatic hyperplasia. Urology. 1998;51:38-45. Roehrborn CG. Alfuzosin: overview of pharmacokinetics, safety, and efficacy of a clinically uroselective
-blocker. Urology. 2001;58:55-63. Steenkamp V. Phytomedicines for the prostate. Fitoterapia. 2003;74:545-552. Thiyagarajan M. Alpha-adrenoceptor antagonists in the treatment of benign prostate hyperplasia. Pharmacology. 2002;65:119-126. Debruyne FMJ. Alpha blockers: are all created equal? Urology. 2000;56(suppl 5A):20-22. O’Leary MP, Roehrborn CG, Andriole G, et al. Improvements in benign prostatic hyperplasia-specific quality of life with dutasteride, the novel dual 5
reductase inhibitor. BJU Int. 2003;92:262-266. VOL. 8 SUPPL. 4 2006 REVIEWS IN UROLOGY S17