Evaluation and Treatment of Lower Urinary Tract Symptoms in Older Men

Transcription

1 Evaluation and Treatment of Lower Urinary Tract Symptoms in Older Men P. Abrams,*, C. Chapple, S. Khoury, C. Roehrborn and J. de la Rosette on behalf of the International Scientific Committee and members of the committees, 6th International Consultation on New Developments in Prostate Cancer and Prostate Diseases Purpose: The 6th International Consultation on New Developments in Prostate Cancer and Prostate Diseases met from June 24 28, 2005 in Paris, France to review new developments in benign prostatic disease. Materials and Methods: A series of committees were asked to produce recommendations on the evaluation and treatment of lower urinary tract symptoms in older men. Each committee was asked to base recommendations on a thorough assessment of the available literature according to the International Consultation on Incontinence level of evidence and grading system adapted from the Oxford system. Results: The Consultation endorsed the appropriate use of the current terminology lower urinary tract symptoms/benign prostatic hyperplasia/benign prostate enlargement and benign prostatic obstruction, and recommended that terms such as clinical benign prostatic hyperplasia or the benign prostatic hyperplasia patient be abandoned, and asked the authorities to endorse the new nomenclature. The diagnostic evaluation describes recommended and optional tests, and in general places the focus on the impact (bother) of lower urinary tract symptoms on the individual patient when determining investigation and treatment. The importance of symptom assessment, impact on quality of life, physical examination and urinalysis is emphasized. The frequency volume chart is recommended when nocturia is a bothersome symptom to exclude nocturnal polyuria. The recommendations are summarized in 2 algorithms, 1 for basic management and 1 for specialized management of persistent bothersome lower urinary tract symptoms. Conclusions: The use of urodynamics and transrectal ultrasound should be limited to situations in which the results are likely to benefit the patient such as in selection for surgery. It is emphasized that imaging and endoscopy of the urinary tract have specific indications such as dipstick hematuria. Treatment should be holistic, and may include conservative measures, lifestyle interventions and behavioral modifications as well as medication and surgery. Only treatments with a strong evidence base for their clinical effectiveness should be used. Key Words: urinary tract, urologic diseases, prostatic diseases THE 6th International Consultation on New Developments in Prostate Cancer and Prostate Diseases met from June 24 28, 2005 in Paris, France, under the cosponsorship of the Union Internationale Contre le Cancer and the International Consultation on Urological Diseases, and in collaboration with the American Urological Association, Confederacion Americana de Urologia, European Association of Urology, International Society of Urology and the Urological Association of Asia to review new developments in prostate cancer, LUTS, benign prostatic disease, prostatitis Abbreviations and Acronyms AR adrenergic receptor BOO bladder outlet obstruction BPE benign prostate enlargement BPH benign prostatic hyperplasia BPO benign prostatic obstruction DAN-PSS Danish Prostate Symptom Score DRE digital rectal examination FVC frequency volume chart ICIQ International Consultation on Incontinence Questionnaire I-PSS International Prostate Symptom Score LUTS lower urinary tract symptoms OAB overactive bladder PSA prostate specific antigen Qmax maximum urinary flow rate QoL quality of life RCT randomized controlled trial TURP transurethral prostate resection Submitted for publication September 24, * Correspondence: Bristol Urological Institute, Southmead Hospital, Bristol BS10 5NB United Kingdom ( edu@bui.ac.uk). Financial interest and/or other relationship with Astellas, Bayer, Novartis, Pfizer, Plethora, AMS, Verathon, Ferring and Merck. Financial interest and/or other relationship with Pfizer, Astellas, Novartis, Allergan and Recordati. Nothing to disclose. Financial interest and/or other relationship with GlaxoSmithKline, VA Corporate Studies, Southwest Oncology Group, Sanofi Aventis, CALGB Clinical Trial group, Lilly COS, NIDDK, Spectrum Pharmaceuticals, Aeterna Zentaris, Pfizer, Amgen, Abbot Laboratories, Bayer Healthcare and Watson Pharmaceuticals. Financial interest and/or other relationship with Galil Medical, BSC and AMS. Editor s Note: This article is the fourth of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 1970 and For another article on a related topic see page /13/ /0 THE JOURNAL OF UROLOGY Vol. 189, S93-S101, January by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC. Printed in U.S.A. S93 Please cite this article as J Urol 2013;189: S93-S101. DOI:

2 S94 LOWER URINARY TRACT SYMPTOMS IN OLDER MEN and chronic pelvic pain syndrome, and other related fields. A full account of the Consultation s work on male lower urinary tract dysfunction has been published in book form. 1 A series of committees collaborated to produce these recommendations on the evaluation and treatment of LUTS in older men. Appendix 1 gives a list of committees, chairs and members, page numbers and number of references (references total in excess of 1,000). Each committee was asked to base their recommendations on a thorough review of the available literature and the global subjective opinion of recognized experts serving on focused committees. The recommendations are graded whenever possible according to the International Consultation on Incontinence level of evidence and grading system adapted from the Oxford system. Full details of this methodology are available. 2 Each committee searched the English language literature to be able to give a level of evidence for the literature for each topic. Four levels of evidence were used (1, 2, 3 and 4) without the subdivisions of the original Oxford system (eg 1a and 1b). Level 1 evidence is when there is a meta-analysis of RCTs or more than 1 good quality randomized trial giving clear and consistent evidence. Level 2 evidence refers to less good quality RCTs, for example when there is less than 80% followup. The level of evidence extends down to 4 when the only evidence is expert opinion without a Delphi process or poor quality trials. Full details of the reviewed literature and references are provided in the book which was published as a full report of the work of the committee, modified by the consultation process that occurred in Paris. 1 The 4 grades of evidence inform the grades of recommendation A, B, C and D. Each can be a positive or a negative recommendation. Grade A recommendations usually depend on level 1 evidence and grade B recommendations on level 2 evidence. Some flexibility in the grading system is needed when there is a large consistent body of evidence, for example, for the efficacy of TURP or extracorporeal shock wave lithotripsy before there were RCTs. The individual committee reports were developed and peer reviewed by open presentation and comment. Final recommendations were then refined by the Scientific Committee which consisted of the chairmen of all the committees. The recommendations apply only to the standard patient as defined. Those outside the definition of a standard patient may require diagnostic evaluation and treatment beyond the scope of these recommendations. These recommendations were agreed on in 2005, and will be periodically reevaluated in light of clinical experience and technological progress. TERMINOLOGY AND DEFINITIONS Lower urinary tract symptoms include storage and/or voiding disturbances which are common in aging men. LUTS may be due to structural or functional abnormalities in 1 or more parts of the lower urinary tract which comprises the bladder, bladder neck, prostate, distal sphincter mechanism and urethra. It must also be remembered that LUTS may result from abnormalities of the peripheral and/or central nervous systems which provide neural control to the lower urinary tract. LUTS may also be secondary to cardiovascular, respiratory or renal dysfunction or disease. This Consultation endorses the previously recommended nomenclature from the 5th International Prostate Consultation detailed in the International Continence Society Terminology Report published in LUTS is divided into 1) storage symptoms which are experienced during the storage phase of the bladder and include daytime frequency and nocturia, and 2) voiding symptoms which are experienced during the voiding phase. The overactive bladder syndrome is defined as urgency with or without urgency incontinence, usually with frequency and nocturia. Detrusor overactivity is a urodynamic observation characterized by involuntary detrusor contractions during the filling phase that 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 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 is the generic term for all forms of obstruction to the bladder outlet (eg urethral stricture) including BPO. Therefore, terms such as BPH patient, symptomatic BPH, clinical BPH, drugs for BPH and BPH treatment are imprecise, cause confusion and are not recommended. The Physicians Desk Reference lists as the indication for alfuzosin and tamsulosin the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH), and for finasteride and dutasteride the treatment of symptomatic benign prostatic hyperplasia in men with an enlarged prostate. It is clear from this discussion that these indications are less than clear. A more appropriate listing of indications would be, Alpha blockers are effective in treating LUTS, while 5 -reductase inhibitors are effective in treating LUTS in men with probable benign prostate obstruction with gland enlargement. The standard patient is a man older than 50 years consulting a qualified health care provider for LUTS. These symptoms may or may not be associated with an enlarged prostate gland, BOO or histological BPH. A

3 LOWER URINARY TRACT SYMPTOMS IN OLDER MEN S95 Figure 1. Basic management of LUTS in men qualified health care provider is a person (physician, physician assistant, nurse practitioner or other mid level provider) knowledgeable in diseases affecting the urinary tract, in particular the prostate gland, who has the expertise to perform the tests required as an initial evaluation, and who has been trained and has demonstrated competence in performing DRE. LUTS consensus recommendations do not apply when other disease pathologies are known to be responsible for the LUTS such as prostate cancer or other genitourinary tract malignancies, or due to significant comorbidities (eg severe diabetes mellitus) or significant concomitant medications, prior pelvic surgery or trauma. In addition to being responsible for the symptoms, these diseases/conditions are likely to affect the proposed treatment in a manner not consistent with the consensus recommendations. DIAGNOSTIC EVALUATION In the classification of diagnostic tests and studies a recommended test should be performed on every patient during the initial evaluation whereas an optional test is a test of proven value in the evaluation of select patients. In general, optional tests are done during a specialized evaluation and usually performed by a urologist. Basic Evaluation and Recommended Tests The basic evaluation should be done on every patient presenting to a health care provider with lower urinary tract symptoms (fig. 1). History. A relevant medical history should be obtained focusing on the nature and duration of reported genitourinary tract symptoms, previous surgical procedures (in particular as they affect the genitourinary tract), general health issues, sexual function history, medications currently taken and patient fitness for possible surgical procedures or other treatments. Assessment of symptoms and bother. At least a semiquantitative assessment of symptoms and bother is strongly recommended to grade the severity of lower urinary tract symptoms and to understand the degree

4 S96 LOWER URINARY TRACT SYMPTOMS IN OLDER MEN of bother caused by those symptoms. Excellent quantitative assessment tools have been developed and validated such as the I-PSS with bother score. Other questionnaires include the DAN-PSS, the ICIQ- MLUTS and the BPH Impact Index. Physical examination and DRE. A focused physical examination should be performed to assess the suprapubic area to rule out bladder distention, and overall motor and sensory function focused on the perineum and lower limbs. DRE should be performed to evaluate anal sphincter tone and the prostate gland with regard to approximate size, consistency, shape and abnormalities suggestive of prostate cancer. Urinalysis. Urine should be analyzed using any of the widely available dipstick tests. These tests are done to determine if the patient has hematuria, proteinuria, pyuria or other pathological findings (eg glucosuria, ketonuria, positive nitrite test etc). Examination of the urinary sediment and culture is indicated if the result of the dipstick is abnormal. The results of urinalysis may guide further and additional testing independent of the evaluation for LUTS. Serum PSA. The benefits and risks of PSA testing should be discussed with the patient including the possibility of false-positive and false-negative results, the possible complications of subsequent transrectal ultrasound guided biopsy, and the possibility of a falsenegative biopsy. In general the PSA test would only be performed if life expectancy is greater than 10 years and if a diagnosis of prostate cancer would modify the management approach. Given the uncertainties surrounding prostate cancer detection physicians must use clinical judgment in determining which patients should or should not undergo transrectal ultrasonography and prostate biopsy in response to a particular PSA. Serum PSA is a reasonable predictor of prostate volume in men with LUTS and can be used in this capacity in clinical decision making. Frequency volume charts. Frequency volume charts (voiding diary or time and amount voiding charts) are particularly useful when nocturia is the dominant symptom. The time and voided volume are recorded for each micturition during several 24-hour periods (usually 3), and help to identify patients with nocturnal polyuria or excessive fluid intake which are common in the aging male. Specialized Evaluation and Recommended Tests Detailed quantification of symptoms by standardized questionnaires. When patients present with LUTS the use of a short, self-administered questionnaire in the appropriate language for the objective documentation of symptom frequency from the patient s perspective is highly recommended (fig. 2). The 3 recommended short, patient completed questionnaires are the I-PSS and the ICIQ-MLUTS, both of which include a single quality of life question, and the DAN-PSS-1. The I-PSS is used to assess the frequency of 3 storage symptoms (frequency, nocturia, urgency) and 4 voiding symptoms (feeling of incomplete emptying, intermittency, straining, weak stream). The bother score assesses the degree of bother associated with the 7 symptoms in the aforementioned I-PSS symptom severity score. The BPH Impact Index can be used with the I-PSS, and has 4 questions asking how the symptoms affect the patient s everyday life and interfere with daily activities, thus capturing the impact of the condition. The results provide useful additional information to the single 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? The ICIQ-MLUTS assesses the frequency and bother of 8 storage symptoms (frequency, nocturia and urgency, plus 5 questions on types of incontinence, that is urgency, stress, unconscious enuresis and post-micturition dribble) and 5 voiding symptoms (feeling of incomplete emptying, intermittency, straining, weak stream, hesitancy). Bother is evaluated usinga0to10linear analog scale. Additional ICIQ modules on QoL (ICIQ-MLUTSqol) and sexual function (ICIQ-Msex) can be used with the ICIQ-MLUTS. The advantage of the ICIQ-MLUTS is that it recognizes and assesses symptoms due to causes other than BPO in the pathogenesis of LUTS such as OAB. Flow rate recording. Urinary flow rate measurement is useful in the initial diagnostic assessment and during or after treatment to determine response. Because of the noninvasive nature of the test and its clinical value, it is recommended as part of the specialized evaluation to be performed before embarking on any active therapy. Qmax is the best single measure but a low Qmax does not distinguish between obstruction and decreased detrusor contractility. Because of the intra-individual variability and the volume dependency of the Qmax, at least 2 flow rates should be obtained, ideally both with a volume greater than 150 ml voided urine. If such a voided volume cannot be obtained by the patient despite repeated recordings the Qmax results at the available voided volumes should be considered. Residual urine. The determination of post-void residual urine is useful in the initial diagnostic assessment of the patient and during subsequent monitoring as a safety parameter. The determination is best performed by noninvasive transabdominal ultrasonography. Because of the marked intra-individual variability of residual urine volume, the test should be repeated to improve precision, particularly if the

5 LOWER URINARY TRACT SYMPTOMS IN OLDER MEN S97 Figure 2. Specialized management of persistent, bothersome LUTS after basic management. Rx, treatment first residual urine volume is significant and suggests a change in the treatment plan. Pressure flow studies. These studies are recommended before invasive therapy in men with a Qmax greater than 10 ml per second. If Qmax is less than 10 ml per second obstruction is likely and pressure flow studies are not necessarily needed. Pressure flow studies are of proven value in the evaluation of patients before invasive therapies, or when a precise diagnosis of BOO is important. Pressure flow urodynamic studies are the only method to our knowledge with the potential to distinguish men with a low urinary flow rate due to detrusor underactivity from those with bladder outlet obstruction. This distinction is made by relating detrusor pressure at maximum urinary flow rate to the maximum flow rate. If patients are found not to have BOO yet have severe LUTS they are less likely to benefit from invasive treatments such as surgery designed to relieve outlet obstruction. Consequently it is recommended that these patients have symptoms treated in an appropriate fashion. Such treatment can be aimed at other underlying disease processes including anticholinergics, bladder behavioral training, biofeedback, etc. The most important parameter of the pressure flow study is detrusor pressure at maximum urinary flow rate. Prostate imaging with transabdominal or transrectal ultrasound. When residual urine is determined by transabdominal ultrasonography with a machine generating real-time B-mode images, prostate shape, size, configuration and protrusion into the bladder may be simultaneously evaluated. Outside

6 S98 LOWER URINARY TRACT SYMPTOMS IN OLDER MEN of this context imaging of the prostate by transabdominal or transrectal ultrasound is optional in selected patients. The success of certain treatments may depend on anatomical characteristics of the prostate gland (eg hormonal therapy, thermotherapy, stents, transurethral incision of the prostate). When such treatments are planned transabdominal or transrectal ultrasonography may be used to assess prostatic size and shape. In men with serum PSA increased above the locally accepted reference range, transrectal ultrasonography is the method of choice to evaluate the prostate and to guide a needle biopsy of suspicious areas, or to perform biopsies to rule out prostate cancer. Upper urinary tract imaging with ultrasonography or excretory urography. Although imaging of the upper urinary tract is not recommended as a routine procedure, it is indicated in patients presenting with 1 or more of the signs or symptoms, or history of upper urinary tract infection, hematuria (microscopic or macroscopic), history of urolithiasis, renal insufficiency (in this case ultrasonography is the preferred imaging study) and recent onset nocturnal enuresis. Endoscopy of lower urinary tract. Endoscopic evaluation of the lower urinary tract is not recommended in an otherwise healthy patient with an initial evaluation consistent with BOO, although it has certain indications as previously described for imaging. There are treatment alternatives in which success or failure depends on the anatomical configuration of the prostate (eg transurethral incision of the prostate, thermotherapy etc). Endoscopy is recommended if considered helpful when such treatment alternatives are contemplated. TREATMENT RECOMMENDATIONS Basic Management If initial evaluation demonstrates the presence of LUTS associated with 1 or more of the findings of DRE suspicious of prostate cancer, hematuria, abnormal PSA, pain, recurrent infection (infection should be assessed and treatment started by the practitioner before referral), palpable bladder or neurological disease, the patient should be referred to a specialist (urologist) for appropriate evaluation before advising treatment (fig. 1). When initial evaluation demonstrates the presence of LUTS only, with or without some degree of nonsuspicious prostate enlargement, if the symptoms are not significantly bothersome or if the patient does not want treatment, no further evaluation is recommended. The patient is reassured and can be seen again if necessary. This recommendation is based on the opinion that this category of patients with nonbothersome LUTS is unlikely to experience significant health problems in the future due to their condition. In patients with bothersome symptoms it is now recognized that LUTS has a number of causes that may occur singly or in combination. Among the most important are BPO, OAB and nocturnal polyuria. The physician can discuss treatment options with the patient based on the results of initial evaluation with no further tests being needed. In primary care there should be a discussion of the benefits and risks involved with each of the recommended treatment alternatives (watchful waiting, medical treatment, interventional therapy, surgical or nonsurgical treatment). The choice of treatment is reached in a shared decision making process between physician and patient. If the patient has predominant significant nocturia and gets out of bed to void 2 or more times per night then he should be asked to complete a FVC for 3 days. The FVC will show 24-hour polyuria or nocturnal polyuria when present, the first of which has been defined as greater than 3 l output. In practice patients with symptoms are advised to aim for a urine output of 1 l/24 hours. Nocturnal polyuria is diagnosed when more than 33% of the 24-hour urine output occurs at night. The patient should be treated according to the nocturia algorithm (fig. 1). If symptoms do not improve sufficiently he should be treated along the same lines as men without predominant nocturia. If the patient has no polyuria and medical treatment is considered the physician can proceed with therapy based mainly on first altering modifiable factors such as concomitant drugs, regulation of fluid intake especially in the evening, lifestyle changes (avoiding a sedentary lifestyle) and dietary advice (avoiding dietary indiscretions such as excessive intake of alcohol and highly seasoned or irritative foods). If treated pharmacologically the patient should be followed to assess treatment success or failure and possible adverse events. The time after initiation of therapy for the assessment of treatment success varies according to the pharmacological treatment prescribed. It is usually 2 to 4 weeks for -blocker therapy and 3 months for a 5 -reductase inhibitor. If treatment is successful and the patient is satisfied followup should be repeated approximately once a year by repeating the initial evaluation as previously outlined. The followup strategy will allow the physician to detect any changes that have occurred in the last year, more specifically, if symptoms have progressed or become more bothersome, or if a complication has developed creating an indication imperative for surgery. If treatment fails and the patient is not satisfied, he should be referred to

7 LOWER URINARY TRACT SYMPTOMS IN OLDER MEN S99 a urologist for further evaluation and possibly interventional treatment. If interventional therapy is chosen the patient should be referred to the specialist. Specialized Management Patients with persistent bothersome LUTS after basic management should receive specialist treatment. The specialist will use additional testing beyond those tests recommended for basic evaluation such as FVC, detailed LUTS questionnaire, urine flow studies and ultrasound estimate of residual urine. If storage symptoms predominate (OAB) and there is no indication of BOO, overactive bladder due to idiopathic detrusor overactivity is the most likely cause if there is no indication of BOO from flow study and ultrasound estimates of post-void residual urine. The treatment options of lifestyle intervention, behavioral modification (bladder training and pelvic floor muscle exercises) and pharmacotherapy (antimuscarinic drugs) should be discussed with the patient. The best results are obtained by combined therapy using all 3 modalities. Should improvement be insufficient and symptoms severe, then newer modalities of treatment such as botulinum toxin and sacral neuromodulation can be considered. If there is evidence of BOO treatment options should be discussed in the categories of drug therapy or interventional procedures. If drug therapy is considered decisions will be influenced by coexisting OAB symptoms and prostate size or serum PSA. If there are coexisting BOO and OAB symptoms then the patient is sometimes treated with -blocker and antimuscarinic combination therapy with increasing evidence of safety and efficacy. When BOO symptoms predominate 1-adrenergic blocking agents are the treatment of choice for LUTS due to BOO. However, combination therapy with a 5 -reductase inhibitor has shown the highest efficacy when the prostate is enlarged and/or if serum PSA is greater than 1.5 ng/ml. The patient should be followed to assess treatment success or failure and possible adverse events. The interval after initiation of therapy for the assessment of treatment success varies according to the pharmacological treatment prescribed, usually 2 to 4 weeks for -blocker therapy and at least 3 months for 5 -reductase inhibitors. If treatment is successful and the patient is satisfied, followup should be repeated approximately once a year by repeating the initial evaluation as outlined previously. The followup strategy will allow the physician to detect any changes that have occurred in the last year, more specifically, if symptoms have progressed or become more bothersome, or if a complication has developed creating an imperative indication for surgery. If treatment fails and the patient is not satisfied, he should be reassessed and other therapies should be considered. Interventional Therapy If the patient elects to have interventional therapy and there is sufficient evidence of obstruction, eg Qmax less than 10 ml per second, patient and physician should discuss the benefits and risks of the various interventions. TURP is still the gold standard for interventional treatment but, when available, new interventional therapies could be discussed. The techniques accepted for clinical use are summarized in Appendix 2. If the patient s condition is not sufficiently suggestive of obstruction, eg Qmax greater than 10 ml per second, pressure flow studies are indicated as treatment failure rates are somewhat higher in the absence of obstruction. If interventional therapy is planned without clear evidence of the presence of obstruction, the patient needs to be informed of possible higher failure rates of the procedure. TREATMENT OPTIONS Criteria for Acceptable Treatment Options For a treatment to be considered an acceptable option it must meet several criteria. Effectiveness and safety of the treatment must have been shown in trials according to the guidelines established by the International Consultation on Prostate Diseases. Any treatment of the disease should improve symptoms and/or prevent long-term complications by shrinking the enlarged prostate, and/or reducing obstruction or by other modes of action. The risks of morbidity and mortality associated with treatment must be considered in the context of the treatment. New interventional treatments should be compared to sham, similar treatments of proven efficacy, or TURP. Pharmacological treatments should be compared to placebo, have minimal morbidity, be acceptable to the patient, should not interfere with patient sense of well-being or quality of life, and must not be unacceptably hazardous to his health. After a new treatment is considered an acceptable treatment option, long-term studies should be conducted to demonstrate durability and continued effectiveness and safety, continued effectiveness relative to existing treatment options, and costeffectiveness related to existing and emerging therapeutic options. The results of such long-term studies could lead to a treatment being firmly established in routine practice or to it being rejected as an unacceptable option. Acceptable Treatment Options The patient must be informed of all available and acceptable treatment options applicable to his clin-

8 S100 LOWER URINARY TRACT SYMPTOMS IN OLDER MEN ical condition, and the related benefits, risks and costs of each modality. LUTS associated with benign prostatic obstruction can significantly affect the quality of life in aging men but are rarely life threatening. Moreover, a significant number of men with histological BPH or even gland enlargement do not have disease progression. Thus, it is reasonable to discuss the benefits, risks and costs of the available treatment strategies with the patient, and have him actively participate in the choice of therapy (shared decision making). Some patients with bothersome symptoms might opt for surgery while others might opt for watchful waiting or medical therapy depending on individual views of benefits, risks and costs. Watchful waiting. Progression of LUTS, BPE and/or BPO in terms of symptoms, future prostate growth and long-term complications has been shown to be more likely in men with larger glands and higher serum PSA (ie 1.5 ng/ml or greater). Many men with smaller glands and/or lower serum PSA may have minimal progression of symptoms over time. Moreover, the level of symptoms individual men may tolerate before being bothered by them is highly variable. Therefore, watchful waiting is an accepted treatment option for patients with mild, moderate or even severe symptoms as long as they are not bothered by them and the imperative indications for surgery have not developed (mainly upper tract dilatation and/or increased creatinine). After being adequately informed of the various treatment options and their consequences, if the patient chooses watchful waiting as the preferred form of management, he should be followed approximately yearly by repeating the initial evaluation as previously outlined. This followup strategy will allow the physician to detect any changes that have occurred in the last year, specifically if symptoms have progressed or become more bothersome, or if a complication has developed, creating an imperative indication for surgery. Medical therapy. Patients initiated on medical therapy should be followed at appropriate intervals by repeating the initial evaluation, assessing treatment success or failure and possible adverse events, and determining whether an alteration in treatment plan is indicated. Once patients are stable on treatment, followup intervals should be at least yearly. Before deciding on a specific medical therapy the physician should discuss the benefits and risks of the available drugs with the patient. -Adrenergic receptor antagonists ( -blockade). 1 -AR antagonists are effective, improve quality of life and have acceptable safety as documented in properly conducted randomized clinical trials. 1 -AR antagonists are an acceptable treatment option for patients with LUTS with bothersome symptoms thought to be due to BPO in whom serious complications have not developed. The long-term efficacy and safety of 1 -AR antagonists have been documented in open label extension investigations but continued study for example of cost-effectiveness is recommended. The clinical efficacy and safety of 1 -AR antagonists cannot be reliably predicted from preclinical data. However, the effects on flow may be predicted. The most advantageous subtype selectivity profile for an 1 -AR antagonist has not been established. Clinical uroselectivity as defined by the International Consultation on BPH ( desired effect on obstruction and lower urinary tract symptoms related to adverse effects ) is still a valid concept. All clinically available 1 -AR antagonists can be associated with dizziness, asthenia and orthostatic hypotension, and have the potential to lower blood pressure. The frequency of 1 -AR antagonist side effects may vary among individual agents, and the choice of a particular 1 -blocker might be influenced by the cardiovascular and sexual status of the patient. Dizziness and asthenia may be mediated by the central nervous system. Adequate head-to-head comparisons among 1 -AR antagonists are still scarce, making fair comparisons among agents difficult. More such studies are needed. The clinical action of 1 -AR antagonists is rapid and treatment success is usually assessed after 2 to 4 weeks of treatment. In patients with BPO and hypertension 1 -AR antagonists remain a first line treatment for BPO. Associated hypertension and cardiovascular diseases should be treated independently according to established guidelines. 5 -Reductase inhibitor therapy. Of the available forms of hormonal therapy (androgen ablation, antiandrogens and 5 -reductase inhibitors) only the 5 reductase inhibitors have demonstrated efficacy and acceptable safety in properly conducted randomized clinical trials. The 5 -reductase inhibitors are less effective in terms of symptom relief and flow rate in men who do not have clinically enlarged prostates. It is considered an acceptable first line treatment option in patients with clinically enlarged prostates and bothersome symptoms in whom serious complications have not developed. The long-term efficacy and safety of 5 -reductase inhibitors have been demonstrated in open label extension investigations but continued study of cost-effectiveness is recommended. Available data show that 5 -reductase inhibitors have a preventive influence on the progression of BPE, and significantly reduce clinically important end points such as acute urinary retention and the need for surgery. 5 - Reductase inhibitors decrease serum PSA but this can be corrected with sufficient clinical accuracy by multiplying the value by 2. To date there is no evidence that

9 LOWER URINARY TRACT SYMPTOMS IN OLDER MEN S reductase inhibitors mask the detection of prostate cancer. The most common side effects of 5 -reductase inhibitors are sexual adverse events (decreased ejaculation, decreased libido and impotence). After initiation of therapy the time for the assessment of treatment success is at least 3 months. Combination treatment. The combination of an -adrenergic receptor antagonist and a 5 -reductase inhibitor (combination therapy) is an appropriate and effective treatment for patients with LUTS associated with demonstrable prostatic enlargement. Alternative treatments. Alternative medical treatment for LUTS mainly includes phytotherapeutic preparations and derivatives of polyene substances. The use of alternative medical treatments for LUTS varies greatly among countries due to the evolution of treatment traditions and structures of the health care systems. In some countries it is regarded as a drug treatment and partly or totally reimbursable, while in others it is not reimbursed but still considered a drug treatment, or merely considered a dietary supplement. Most phytotherapeutic preparations are plant extracts with various components manufactured by various extraction procedures, which complicates their comparison despite originating from the same plant. Progress has been made toward isolation of components of these preparations and their possible mechanism(s) of action. Randomized clinical studies against placebo have been conducted with 1 extract of Serenoa repens (Permixon extract) and suggest superior efficacy against placebo. Comparative studies of this extract with other medical treatments are not conclusive because they do not include a placebo arm. Other products (extracts from Pygeum africanum, preparations containing high concentrations of -sitosterol and mepartricin) have not been evaluated in studies adequate to draw significant conclusions. Further studies according to the guidelines of the International Consultation are needed. Long-term followup is lacking. These studies are encouraged as the Consultation considers this approach an interesting direction for further pharmaceutical and clinical research. Interventional therapies. Standard surgical approaches produce the most significant, long-term symptom improvement with acceptable risks. However, there is increasing acceptance of minimally invasive therapies that produce variable degrees of symptom improvement with risks that (in some cases) may be less than those of surgery. However, evidence of durability is lacking and it remains uncertain whether these new technologies are more cost-effective in the long term than standard surgery (eg TURP). The present status of the various available techniques is summarized in Appendix 2. APPENDIX 1 Committees with page numbers LUTS: Etiology and Patient Assessment ABRAMS P. United Kingdom (Chair), D ANCONA C. Brazil, FOO K. T. Republic of Singapore, GRIFFITHS D. United States, NISHIZAWA O. Japan, NITTI V. United States, TUBARO A. Italy, VAN KERREBROECK P. The Netherlands, WEIN A. United States. Pages , 401 references. New Medical Developments in the Management of LUTS in Adult Men ARTIBANI W. Italy, BERGES R. Germany, CHAPPLE C. United Kingdom (Chair), KAPLAN S. United States, MICHEL M. C. The Netherlands, PERRIN P. France, PREZIOSO D. Italy, TAKEDA M. Japan, TAMMELA T. L. Finland, TEILLAC P. France. Pages , 358 references. New Minimally Invasive and Surgical Developments in the Management of BPO BABA S. Japan, BADLANI G. United States, DE LA ROSETTE J. The Netherlands (Chair), ELHILALI M. Canada, GRAVAS S. Greece, JEVTICH H. M. United States, MUSCHTER R. Germany, NAITO S. Japan, NETTO N. R. Brazil. Pages , 217 references. Prevention of BPH Outcomes and Clinical Progression EMBERTON M. United Kingdom, GIULIANO F. France, HIRAO Y. Japan, JARDIN A. France, KEUPPENS F. Belgium, O LEARY M. United States, ROEHRBORN C. United States (Chair), ROSEN R. United States. Pages , 64 references. APPENDIX 2 Clinically acceptable interventional techniques Conventional and novel treatments for BPO, and recommendations about their use in international guidelines Interventional therapies Abbreviation International Consultation on BPH 2005 Transurethral resection of the TURP Acceptable prostate Open prostatectomy OP Acceptable Transurethral electrovaporization TUVP Acceptable Laser vaporization LV Acceptable Transurethral microwave therapy TUMT Acceptable Transurethral needle ablation TUNA Acceptable Interstitial laser coagulation ILC Acceptable Urethral stents Acceptable with restriction REFERENCES 1. Male lower urinary tract dysfunction: evaluation and management. In: 6th International Consultation on New Developments in Prostate Cancer and Prostate Diseases. Edited by J McConnell, P Abrams, L Denis, S Khoury and C Roehrborn. Paris: Health Publications Abrams P, Khoury S and Grant A: Evidence-based medicine overview of the main steps for developing and grading guideline recommendations. Prog Urol 2007; 17: Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U et al: The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn 2002; 21: 167.