Hardly any area of interest in urology has undergone as much change in the therapeutic armamentarium over the past decade as the treatment of lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). In the past, surgical management, most commonly transurethral resection of the prostate (TURP), was the mainstay of treatment for all patients with bothersome symptoms. The 1990s brought an array of medical interventions as well as modifications of traditional surgery and minimally invasive treatments, including transurethral microwave thermotherapy (TUMT), transurethral needle ablation of the prostate (TUNA), and others. Some have already been forgotten.
In the summer of 1991, a meeting was organized in Paris, France, to bring together experts from around the world to prepare reports and make recommendations on the most pressing issues in what then was called “prostatism” and BPH: basic sciences, epidemiology, pathophysiology, diagnosis, and therapeutic management. Within a year of the meeting, proceedings were published and became quickly one of the most widely utilized reference books in the field. New developments prompted additional consultations in alternating years, and the 5th International Consultation on BPH convened again in Paris from June 25th through June 27th, led by Dr. Aso (Japan) as honorary president, Professor Chatelain (France), and three Vice Chairmen, Professor Denis from Belgium, Professor Foo from Singapore, and Dr. John D. McConnell from the USA.
The fourteen committees were led by international experts and consisted of recognized opinion leaders in the field. The committees presented their findings and recommendations to the other panels as well as to the large international audience at the Palais de Congres in Paris. The committees dealt with the epidemiology and natural history of BPH (Chairman, Professor P. Boyle), the economics of BPH (Chairman, Dr. M. Naslund), regulation of prostate growth (Chairman, Professor C.H. Lee), pathophysiology of bladder obstruction in aging men (Chairman, Professor J. Nordling), initial evaluation of LUTS (Chairman, Dr. M. Resnick), quantification of symptoms, quality of life, and sexuality (Chairman, Dr. M. Barry), the urodynamics of LUTS (Chairman, Mr. P. Abrams), detection of prostate cancer in patients with BPH (Chairman, Dr. M. Brawer), clinical research criteria (Chairman, Dr. C. Roehrborn), interventional therapy (Chairman, Professor F. DeBruyne), endocrine treatment (Chairman, Professor G. Bartsch), alpha-blocker therapy (Chairman, Professor A. Jardin), other medical therapy (Chairman, Professor K. Dreikorn), and educational issues (Chairman, Dr. J. Corriere). After the individual committees gave their recommendations, the committee Chairmen met again in closed session to develop recommendations regarding the diagnosis and treatment of LUTS and BPH in a consensus process.
Rapid developments in the field have mandated frequent updates, and the year 2000 was no different. The current recommendations will no doubt also have to be periodically re-evaluated in the light of clinical experience and technological progress.
Nomenclature
A great deal of discussion centered on nomenclature. The term “prostatism” had been eliminated largely due to the recognition that it conveys a false sense of specificity of the symptomatology to the prostate, while in fact the same symptoms can be caused by other organs in the lower urinary tract as well. Instead, the term “lower urinary tract symptoms” (LUTS), popularized originally by Professor Abrams, by now has been accepted nearly worldwide. It is appropriate for two reasons: one, it refers globally to different combinations of both irritative and obstructive, or filling and voiding symptoms, encountered so frequently in aging men. Secondly, the term does not pretend to assign a cause and effect relationship of the symptoms to any specific organs, ie, prostate, bladder neck, bladder, or urethra.
LUTS in aging men are frequently caused by an enlargement of the prostate. However, the term “benign prostatic hyperplasia” (BPH) implies a benign nature and a specific histopathological diagnosis, which rarely is established by diagnostic evaluation prior to embarking on therapy. Thus, it was felt that a hierarchy of more and more specific diagnostic terms should be established to identify to what degree the physician, or in the case of research studies, the investigator, has characterized the patient or his study population. The Consensus Committee particularly believed that the reporting of research studies in biomedical journals would benefit from a more descriptive terminology allowing the reader to know to what degree the patient population has been diagnostically evaluated and classified.
LUTS describes a combination of irritative and/or obstructive voiding disturbances very commonly found in aging men. These may be associated with an enlarged prostate gland (EPG), suspected or urodynamically proven bladder outlet obstruction (BOO), and/or a specific histopathological entity characterized by stromo-glandular hyperplasia of the prostate known as benign prostatic hyperplasia (BPH). The association of any of these entities does not necessarily imply a causal relationship, although LUTS may be caused by an enlarged prostate, which in turn can be responsible for BOO. The symptoms, enlargement and obstruction, are not specific to benign tissue characteristics of the prostate, and strictly speaking, the term “BPH” should be reserved for those men in whom a reasonable attempt was made to rule out the presence of prostate cancer.
Following this logic, the Materials and Methods section of a research publication could therefore contain any one of the following definitions:
Men between the ages of xx and yy years were studied cross-sectionally or longitudinally. This definition would apply to a population-based cross-sectional or longitudinal epidemiological study in which no specific criteria other than male sex and the age of the patient are used as inclusion/exclusion criteria.
Men between the ages of xx and yy years with lower urinary tract symptoms / bothersome lower urinary tract symptoms / LUTS and an I-PSS score of greater than zz points… This definition applies to a study of men between certain age brackets who already are diagnosed with symptoms either of any severity, a qualitative severity, or a numerically or quantitative severity.
Men between the ages of xx and yy years with lower urinary tract symptoms (see above) and an enlarged prostate gland (EPG) (by digital rectal examination) (DRE)/transrectal ultrasonography (TRUS)/magnetic resonance imaging (MRI)… This definition applies to men within a certain age bracket, with LUTS, and a prostate gland enlargement either defined by DRE, TRUS, MRI, or other imaging modalities with or without an implied threshold.
Men between the ages of xx and yy, with LUTS, an enlarged prostate gland, and bladder outlet obstruction (BOO) as defined by a maximum urinary flow rate of less than zz ml/sec/on the basis of a pressure-flow urodynamic study. This definition applies to patients within a certain age bracket with symptoms of a defined severity and an enlarged prostate above a certain threshold who in addition also have bladder outlet obstruction either suspected based on non-invasive flow rates or diagnosed by invasive pressure-flow studies.
Men between xx and yy years with LUTS, EPG, suspected/diagnosed BOO, and clear evidence of benign prostatic hyperplasia (BPH) based on serum PSA testings/transrectal ultrasound guided prostate biopsy (TRUS biopsy). This definition in addition implies that a cancerous condition was ruled out either by serum PSA measurement or by TRUS biopsy.
Diagnostic Recommendations
As in prior consultations, specific recommendations regarding diagnostic evaluations and tests were made. Diagnostic studies were classified as recommended, optional, and not recommended. The feeling of the consensus committee is that a recommended test should be done on every patient during the initial evaluation, while an optional test is of proven value in the evaluation of selected patients only. Some of these optional tests are restricted to the use by a specialized health care provider such as a urologist. Tests not usually recommended are those that have no proven value in the evaluation of most patients, although they can be of some help in selected patients.
The standard evaluation recommended by the Consensus Committee does not apply to men who are at risk for diseases other than the typical scenario of LUTS secondary to EPG, with or without BOO, and with associated BPH. These men are:
Less than 50 years of age
Have prostate cancer
Had prior unsuccessful therapy for LUTS and BPH
Have diabetes mellitus with poor control of disease and suspected or proven diabetic neuropathy
Have a physical examination or other tests suggesting a neurological disorder
Have a history of prior pelvic surgery by trauma
Have a history of sexually transmitted disease suggestive of a urethral stricture disease
Take drugs that have the potential to affect function of the bladder and/or lower urinary tract
Recommended Diagnostic Tests
Tests that should be performed on every patient presenting with LUTS include an adequate medical history focusing on the nature and duration of the symptoms, prior surgical procedures, general health issues, issues of sexual function or dysfunction, medications currently taken, and the patient’s fitness for possible surgical intervention as needed.
Furthermore, the initial evaluation should include a quantification of symptoms. This can best be accomplished by administering the International-Prostate Symptom Score (I-PSS) with an additional quality of life assessment. While there are many tools available to determine the symptom frequency and severity, the I-PSS is currently the most widely utilized instrument of its kind. It has been translated and linguistically validated in many languages, and thus represents a universal tool allowing researchers from around the world to compare results of epidemiological and treatment outcome studies.
The single question added oftentimes to the I-PSS pertaining to the disease-specific quality of life (“If you were to live with your urinary condition the way that it is right now, how would you feel about that?”) with the answers ranging from delighted to terrible (0 to 6 points) is simple to administer and easily understandable. Although it does not capture the global impact of lower urinary tract symptoms on the disease-specific quality of life, the Consensus Committee believes it offers a valuable starting point for a conversation between patient and physician.
An integral part of the initial recommended testing is the physical examination inclusive of a digital rectal examination (DRE). This examination should also include an assessment of the suprapubic area to rule out bladder distension, and a brief neurological examination assessing overall motor and sensory function. The DRE must be performed to evaluate anal sphincter tone and prostate gland regarding the size, consistency, shape, and abnormalities suggestive of overt or locally advanced prostate cancer.
Urinalysis is also recommended to exclude hematuria, proteinuria, pyuria, or other pathological findings. This can be done either by a dipstick test or by a urinary sediment after centrifugation.
In prior consultations, the issue of serum prostate-specific antigen (PSA) testing was hotly debated. From a pragmatic point of view, most patients presenting to a health care provider with LUTS suggestive of EPG, BOO, and BPH, have already had a PSA testing done. In past years a routine PSA test was not recommended as a first-line test in men with LUTS and suspected EPG, BOO, or BPH. Now, however, the Consensus Committee feels that serum PSA measurement should be recommended if the patient has an anticipated life expectancy of over 10 years and, specifically, when the diagnosis of prostate cancer if established would change the treatment plan. The benefits and risks of PSA testing should be discussed. These include the possibility of all positive and negative test results, the possible complications of subsequent TRUS biopsy, and the possibility of a false-negative biopsy.
Another diagnostic tool, frequency-volume charts, had also been discussed in prior meetings. At this conference the charts were recommended as a baseline tool specifically for patients in whom nocturia is the dominant symptom. It has long been felt by experts in the field that patients with nocturia would benefit from filling in a frequency-volume chart over one or several 24 hour periods to help identify patients with nocturnal polyuria or excessive fluid intake, which is not uncommon in aging men.
Optional Diagnostic Tests
It may be a surprise that tests such as urinary flow rate recordings and residual urine measurements are listed as optional tests. However, it is clear that not every physician and health care provider engaged in the evaluation and treatment of men with LUTS and suspected EPG, BOO, and BPH has immediate access to a flow rate meter and/or an ultrasound apparatus to determine residual urine. Further, the measurement of residual urine by insertion of a catheter was considered too invasive, given the trade-off in terms of diagnostic information gained. Thus, the Committee felt that a urinary flow rate measurement is recommended during the initial diagnostic assessment, and during or after treatment to determine response to therapy. This measurement was also endorsed prior to embarking on active therapy such as minimally invasive treatments and/or surgery. As in the past, the peak or maximum urinary flow rate as it is better referred to, is a single most useful measure, although a low maximum urinary flow rate does not allow distinguishing between obstruction and decreased bladder contractility. For reasons of validity, it was felt that patients should ideally have a voided volume of more than 150 mL.
Residual urine suffers from great individual variability. Efforts to link increased amounts of residual urine to unfavorable outcomes such as acute urinary retention, urinary tract infections, or deterioration of the upper tract with subsequent renal insufficiency have by and large failed. If residual urine measurements are performed, the least invasive route, that is to say, transabdominal ultrasonography should be utilized.
Invasive pressure-flow urodynamic studies offer the best and only way to differentiate between bladder outlet obstruction (BOO) and a failing detrusor muscle. The most common way of assessing degrees of obstruction is the Abrams-Griffiths nomogram where patients are divided into those clearly obstructed with very high detrusor pressure and low maximum urinary flow rates versus those unobstructed with good flow rates and low pressures, leaving a certain cohort of men in the equivocal or undetermined range. Recently, the Abrams-Griffiths nomogram was revised and the number of men falling into the equivocal range greatly diminished. Considering the cost, possible morbidity, and impact that the degree of obstruction has on the outcomes of surgical interventions for LUTS and BPH, it is felt that those patients electing to proceed with invasive therapeutic options would benefit most from pressure-flow urodynamic studies.
Tests Recommended Only in Selected Patients
Recent evidence suggests that the success or failure of certain interventions may depend on the size and shape or other anatomical characteristics of the prostate. Further, the actual size of the prostate has been shown to predict the natural history of the disease in terms of deterioration of symptoms, flow rate parameters, and episodes of acute urinary retention and the need to have surgery. Recognizing this, prostate imaging by either transabdominal or transrectal ultrasonography (TRUS) or by MRI imaging, while not recommended for all patients, should be employed in selected patients embarking on such therapies. Further, in men with elevated serum PSA levels, TRUS guided biopsies are clearly the method of choice to further distinguish between BPH and prostate cancer as the underlying cause for the symptoms.
Imaging of the upper urinary tract by either ultrasonography or intravenous urography is recommended in patients with a history of urinary tract infection, hematuria, a history of urolithiasis, renal insufficiency (preferred imaging study, ultrasonograpy). It is not, however, endorsed for an otherwise healthy man in whom the initial evaluation is clearly consistent with uncomplicated LUTS associated with EPG, BOO, and BPH. Numerous case series have been published in the peer-reviewed literature demonstrating the diagnostic yield of systematic use of IVU or upper tract ultrasonography does not justify the use of such imaging modalities in each and every patient.
As in prior consultations, endoscopic evaluation of the lower urinary tract (cystoscopy) is not recommended. It is indicated only if it would have an impact on the choice of treatment and/or the outcome of the therapeutic intervention. Obviously, patients choosing surgeries such as TUIP, TURP, or any other form of energy tissue ablation will undergo endoscopy at the time of the surgery.
Management After Initial Evaluation
If the initial evaluation leads to the suspicion of another underlying disease complex, obviously further evaluations should be conducted to establish the final diagnosis and to render appropriate therapy. If, however, the evaluation is consistent with LUTS associated with EPG, BOO, or BPH, further management depends on the presentation. Certain imperative indications for surgical treatment are recognized. These include urinary retention following at least one attempt of voiding after catheter removal, renal failure clearly due to EPG and BOO, bladder stones clearly due to EPG and BOO, recurrent urinary tract infections clearly due to EPG and BOO, large bladder diverticula interfering with proper drainage from the upper urinary tract, etc. While gross hematuria had in the past constituted a clear indication for immediate surgical intervention, it is now recognized that treatment with the 5α-reductase inhibitor finasteride may be of some utility in these patients. Therefore, only patients who are refractory to therapy with finasteride or who have gross hematuria with clots are considered in urgent need of surgical intervention. Other patients may be referred for a treatment trial with a 5α-reductase inhibitor.
In patients without imperative indication for surgery, the degree of bother and interference with daily activities as a result of the symptoms should be discussed. The decision on whether to proceed with therapy or pursue a course of watchful waiting (i.e., have the patient re-evaluated in approximately 12 months) should be reached in a joint session between patient and health care provider. This shared decision process should include a detailed numerical discussion of benefits and risks involved with the treatment choices available for this specific patient. In addition, the benefits and risks of optional diagnostic tests or tests recommended only for selected patients should be discussed with those patients for whom they are applicable (e.g., pressure-flow studies).
The Committee established clear criteria for acceptable treatment options, those being:
Effectiveness and safety of the treatment must have been shown in trials following guidelines established by the International Consultation on BPH.
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Any treatment of this disease should meet at least one or more of the following aims:
improving the symptoms,
shrinking the enlarged prostate,
reducing obstruction, and/or
preventing long-term complications.
The risk of morbidity and mortality associated with the treatment must be acceptable in the context of the treatments and the expected outcome.
New interventional treatments must be compared to a sham therapy or a similar treatment of proven efficacy (eg, TURP).
Pharmacological treatments should be compared to placebo, have minimal morbidity, be acceptable to the patient, and should not interfere with the patient’s sense of well being, quality of life, and certainly not be hazardous to his health.
After a new treatment is considered as an acceptable option, long-term studies should be done to demonstrate durability, continued effectiveness and safety, continued effectiveness relative to existing treatment options, and cost-effectiveness relative to existing and emerging therapeutic options.
Acceptable Treatment Options
Watchful waiting. Multiple longitudinal epidemiological studies, and observations made in placebo-controlled cohorts of long-term, randomized trials have demonstrated that many patients can be followed conservatively, ie, without specific therapeutic interventions. For those patients, it is safe to be seen once a year and undergo the same standard evaluation as outlined above. Watchful waiting should not be considered as “no management,” but rather as an active surveillance after a discussion between the health care provider and the patient.
Medical therapy. It was the feeling of the Consensus Committee that both alpha adrenergic receptor blockers and 5α-reductase inhibitor therapy are acceptable treatment options. Specific committees during the consultation have focused on the evaluation of all recent literature regarding these two classes of drugs and specific recommendations will be available in the reports of these committees and the subsequent proceedings volume.
Regarding phytotherapeutic agents, short-term randomized trials suggesting clinical efficacy and safety have been reported for some of the numerous compounds. However, there are several problems regarding the use of these preparations. For one, the production is generally not controlled by the health authorities in the various countries, but rather they are sold as food supplements. Thus, issues of purity, content declaration, and batch-to-batch and lot-to-lot variability are addressed not at all or only poorly. Further, a clear pathophysiological rationale and mechanism of action is still lacking for many of the preparations, and the basic and translational research conducted oftentimes is controversial. In some instances, translational research has been done utilizing supraphysiological dosages of these preparations, achieving tissue levels in the prostate and genitourinary tract organs that could never be achieved by the recommended dosages for human consumption. The Consensus Committee recommends therefore the conduct of studies following the recommended guidelines of the International Consultation.
Interventional therapies. Standard surgical approaches produce the most significant long-term symptomatic improvement with minimal or low risks. However, there is an increasing acceptance of minimally invasive therapies; these produce variable degrees of symptomatic improvement with risks less than those of surgical interventions. Some evidence of durability is lacking, however, and it remains uncertain which one of these technologies will withstand the test of time. The Consultation condemned the use of balloon dilation and hyperthermia achieving temperatures of less than 45°C in the prostate as acceptable. The following is a list of interventions recommended as acceptable therapeutic options in either all or selected patients:
Urethral stents: acceptable in high-risk patients.
Thermotherapy with temperatures greater than 45°C: acceptable therapeutic options, treatment selection still requires refinement. Re-treatment rates, durability, and cost-effectiveness data are missing.
Transurethral Microwave Thermotherapy (TUMT), Transurethral Needle Ablation (TUNA), Laser Coagulation Technique, and High Intensity Focused Ultrasound (HIFU) are all interventional therapies based on heat ablation of tissue and thus categorized as thermotherapy. Of these, however, HIFU is not a recommended treatment option at this time as there is no commercially available equipment available.
Transurethral Incision of The Prostate (TUIP) Transurethral incision of the prostate is still an underutilized but highly effective modality with minimal morbidity. The effect can be fundamentally achieved by electrocautery and/or by laser energy.
Tissue Ablative Techniques Transurethral resection of the prostate by either electrocautery, Holmium laser, or electrovaporization, are all acceptable treatment modalities. Depending on the size of the prostate, open enucleation of the prostatic adenoma still remains a useful therapeutic option.
Standard Evaluation of New Treatments in Clinical Trials
One of the 14 committees specifically discussed research criteria and made recommendations regarding the evaluation of treatment modalities in clinical trials. It is the feeling that all drugs and devices being investigated for use in men with LUTS and EPG, BOO, and/or BPH should undergo rigorous testing in phase III clinical trials. In such trials, they should be compared to standard treatments or placebo-sham to document their efficacy. It is further recognized that for commercial products, these trials may be sponsored by the patent holder, owner, device manufacturer or pharmaceutical industry. However, in such cases, third party monitoring of all trial-related source documents at each investigational site is mandatory to avoid conflicts of interest or the appearance thereof.
Additional phase IV clinical trials to document long-term efficacy and safety are highly recommended. All trials must follow the principles of the newly revised Declaration of Helsinki and must be approved by either a central or the local institutional review board (IRB). Trial planning, design, conduct and data analysis should be done in close consultation with biostatisticians to assure proper sample size and power calculations, as well as the appropriate analysis of the outcomes of efficacy parameters. In such trials, all investigators are encouraged to make use of widely available validated instruments such as the I-PSS, the QOL questionnaire, and other instruments, which are widely available and will make the data more transparent to the readership of biomedical journals.
Regarding the reporting of trials, several standards have been published and should be followed (JAMA 1994;272:1926–1931; JAMA 1997;277:927–934).
Information on how to obtain the full proceedings volume can be obtained through Professor Saad Khoury, M.D., Hopital de la Pitie, Urologie, 83 Blvd. de L’Hopital, Cedex 13, Paris 75634, France, Phone: 33 1 42 17 71 20, Fax: 33 1 42 17 71 22, Email: khoury@pzatique.fr.
Main Points.
Diagnostic tests were classified as recommended, optional, or not recommended (except in special cases). Recommended tests/techniques included patient histories, quantification of symptoms, physical exam including a digital rectal exam, urinalysis, a PSA test (in many cases), and frequency-volume charts for patients with nocturia.
In patients for whom surgery is not clearly imperative, the conference noted a number of elements that should be part of the shared decision process between provider and patient on what, if any, therapy should be adopted.
Acceptable treatment options include watchful waiting, both alpha adrenergic receptor blockers and 5α-reductase inhibitor therapy, urethral stents (for high-risk patients), thermotherapy with temperatures greater than 45°C, transurethral incision of the prostate (TUIP), and tissue ablative techniques.
The consultation endorsed nomenclature reforms aimed at achieving greater precision.