Perplexing Problem of Persistently Painful Prostatitis

Treatment Update

TREATMENT UPDATE Perplexing Problem of Persistently Painful Prostatitis J. Curtis Nickel, MD, FRCSC Queen’s University, Kingston General Hospital Kingston, Ontario, Canada Chronic prostatitis has been a perplexing problem for urologists for decades. This review explores the perils and pitfalls urologists encounter with epidemiology, etiology, classification, diagnosis, and treatment of this syndrome. The major question involves the problem of developing rational treatment plans for patients with a medical condition associated with genitourinary pain, variable voiding, and sexual dysfunction but no obvious and accepted etiology. Exciting, innovative, ongoing research does offer some solutions and management strategies that urologists can even now incorporate into their practice while waiting for the fundamental questions to be answered. [Rev Urol. 1(3):160-169] __________________________________________________________________ Key words: Prostatitis, chronic • Chronic pelvic pain syndrome • Prostate ost urologists acknowledge that prostatitis, especially the chronic prostatitis syndromes, is the most frustrating and difficult clinical problem to deal with in urology.1 The etiology for the patients’ pain and other symptoms is unclear. Our traditional classification system is not helpful. Our “gold standard” diagnostic workup has been abandoned by the majority of urologists. Finally—and most important—our treatment is truly dismal. This review will examine the problems with chronic prostatitis we encounter in urology, suggest answers that may alleviate these problems, and explore exciting future initiatives for management of this disease. M Pitfalls and Perils of Prostatitis The Problem Physician. Urologists, as a profession, tend to treat prostatitis as the black sheep of the prostate family of diseases. We perhaps feel that, if we ignore it, it will go away. We certainly hide this disease well, both from ourselves, the rest of the medical profession, and the public. While we trumpet our advances in prostate cancer, benign prostatic hyperplasia (BPH), stones, transplantation, and impotence, we have largely ignored our ignominious failures in prostatitis. Urologists’ personal approaches to prostatitis fall into 6 categories: 1. The Nihilist—Doesn’t believe prostatitis really exists as a disease entity, so doesn’t have to see it or have to treat patients with it. 2. The Traditionalist—Prescribes antibiotics for those few patients in whom a 160 REVIEWS IN UROLOGY SUMMER 1999 Prostatitis positive uropathogen is cultured in the prostatic secretion and discharges the rest as having a nonurologic problem. 3. The Antimicrobial Prescriber— Will prescribe antibiotics (independent of culture results, if one was ever done), one by one until he or she has prescribed all that are available. Then he either starts all over or discharges the patient. 4. The Urodynamicist—Believes that symptoms are due to subtle urinary obstruction that can only be evaluated and ameliorated by adhering to sound urodynamic principles. 5. The Interventionalist—Truly believes that all problems in the lower urinary tract can be dealt with by surgery. This urologist, a surgeon’s surgeon, feels that once he has operated on the patient, there is nothing further he can do, and he therefore discharges the patient. 6. The Committed Urologist—Will use any and all investigations and potential beneficial treatments to help each individual patient. He does not abandon his patients but becomes frustrated with his impotence to deal with the majority of patients’ very real complaints and concerns. This review will be of most value to the last group of urologists, but it is likely that all urologists yearn for a better understanding of this disease and will be happy to incorporate an effective management strategy into their therapeutic armamentariums. The Problem Patient. We are all too familiar with this patient. He is a young man with a long history of waxing and waning genitourinary complaints that include genitourinary pain, variable obstructive and irritative voiding symptoms, and, perhaps, some sexual complaints—in particular, pain on ejaculation. His cultures, while showing various gram-positive organisms, have always been negative for gram-negative uropathogens. His cystoscopy examinations have been normal; ultrasound studies (including transrectal ultrasound done out of sheer frustration) are likewise normal. He has been on multiple courses of antibiotics without benefit. He is frustrated, desperate, and angry, and, more recently, this well-informed patient comes to the urologist with a stack of information downloaded from the Internet. Most urologists will acknowledge that this is a problem patient. The Numbers Problem. Urologists have always been aware that there appeared to be a significant number of patients with prostatitis in the community. Until the last several years, we did not have any data on those numbers and were never sure whether, in the men at risk, the numbers were large or whether it was the classification system admit freely that their consensus was based on personal experience, opinion, and anecdote, and discussion was carried on by telephone and mail. Published as a single, 1-page commentary, it was such an advance over what we had and was written by such distinguished urologists that it became accepted as urologic dogma. But it was acknowledged at the time—and still is—as problematic. We have not been able to validate any distinguishing difference between chronic bacterial and chronic nonbacterial prostatitis because of the difficulty in deciding which bacteria are pathogenic in the prostate gland. The labeling of at least 50% of patients with prostate disease (prostatodynia) when the The labeling of at least 50% of patients with prostate disease (prostatodynia) when the symptoms may not be associated with prostate problems at all has led to mismanagement strategies for these patients in clinical practice. same uncured patients returning for multiple repeat visits. Until the epidemiology of the disease was examined and the effect on the patient’s personal quality of life as well as the effect and cost to society in general were examined, no one was sure he wanted to devote time, energy, and, most importantly, money to the problem of prostatitis. The Problem With Our Classification System. In 1978, a group of prominent urologists decided it was better to define the patient with prostatitis by developing a classification system for the disease.2 This concept was based on the pioneering work of Meares and Stamey,3 who developed the 4 glass test to quantitatively differentiate culture and microscopy results in fluid collected from the various levels of the lower urinary tract. As will be discussed in the next section, this gold standard method is a problem in itself. The originators of our traditional symptoms may not be associated with prostate problems at all has led to mismanagement strategies for these patients in clinical practice. There are also the many questions raised about the so-called gold standard test that must be employed to use this classification. A Diagnostic Problem. In 1968, Meares and Stamey3 published their landmark paper on the technique of lower urinary tract localization for prostatitis. It was hailed then and for many years as a great advance in our understanding of prostatitis. It was to lift us out of the quagmire that prostatitis was slipping into and would allow modern laboratory and clinical evaluation, clinical differentiation, and, finally, treatment rationalization. Unfortunately, after 3 decades of reflection, it has really not allowed us to reach any of these lofty goals. In fact, how important an advance was it? In the 1920s, Van Lackum4 and later Nickel5 described in great detail SUMMER 1999 REVIEWS IN UROLOGY 161 Prostatitis continued (and with many thousands of patients) the technique of bacteriologic culture of lower urinary tract specimens. Meares and Stamey3 just added the voided bladder 1 (VB1) or urethral specimen to the mix. It is admirable to examine such specimens for indicators of urethritis, but most cases can be diagnosed clinically and confirmed with examination of a urethral swab specimen. There can be no doubt (but still great controversy) that occult urethral infection can coexist with prostatitis; therefore, a positive VB1 finding should not rule out prostatitis. The initial landmark paper on the 4 glass localization technique by Meares and Stamey3 The Problem With Treatment. Although many sporadic reports of treatments for patients with prostatitis can be found in the literature, the studies are usually small, uncontrolled, and poorly designed or the case reports cannot be compared with each other.1 Good systematic reviews or a meta-analysis on treatment options in prostatitis is impossible at this time. As a result, each physician relies on his or her interpretation of what he has read, been taught (probably by equally opinionated teachers), and observed, and then, based on his anecdotal experience, formulates a treatment strategy that appears to work in his practice. As It might be appropriate, but there has been no validation that culture and microscopy of semen accurately reflect what is going on in the prostate. described just 6 patients in detail: 1 with an obvious acute urethritis; 1 with acute bacterial prostatitis; and only 4 with a chronic prostatitis syndrome. Of the 4, these investigators only obtained enough expressed prostatic specimen (EPS) for culture from 1 patient. Yet this invalidated technique became the gold standard. A further problem with this technique developed. While it was accepted as urologic dogma, it was not universally employed by urologists. It was described as too difficult, too cumbersome, too time consuming, and, generally, it was felt to provide a low positive yield and too many false positives and false negatives.1,6 Others have resorted to using more easily collected semen ejaculate specimens as a surrogate for prostate fluid. It might be appropriate, but there has been no validation that culture and microscopy of semen accurately reflect what is going on in the prostate. Yes, there is a major problem with diagnosis of the prostatitis syndromes. 162 REVIEWS IN UROLOGY SUMMER 1999 suspected, this cannot serve the patient, the physician, or the disease well, and we are left with the conclusion that we have a major problem with treatment. Our therapeutic results in treating patients with chronic prostatitis can generally be described as dismal. Practical Answers to Our Problems Epidemiology of Prostatitis—A Beginning. Recent epidemiologic studies confirmed that prostatitis is a major male health issue. In the early 1990s, 2 million office visits per year were recorded in the United States for prostatitis.7 Eight percent of urologists’ office visits and 1% of family physicians’ office visits were for prostatitis. Urologists in Wisconsin saw an average of 173 (median, 100) patients with prostatitis per year,8 while Canadian urologists treated 262 (median, 132) such patients per year.9 Thirty-eight percent of these were patients in their practice newly diagnosed with prostatitis.9 The incidence and prevalence of prostatitis ranges between 5% and 8%.8-11 The quality of life of a patient with chronic prostatitis is similar to that of a patient with a recent myocardial infarction, unstable angina, or active Crohn’s disease.12 While the effect on society of this very common disease of young, productive men has not been calculated, it must be enormous. A New Classification System—A Good Start. In 1995, the National Institutes of Health convened a concensus conference to determine future directions in the management of prostatitis.13 It was decided that before any further work could be done, a generally accepted classification system based on no preconceived notions would be used for further examination of this disease. The classification system that was decided on is one that could be useful in clinical practice as well. It divides the prostatitis syndrome into 4 categories. • Category I is that disease we have called acute bacterial prostatitis. There is no doubt that acute bacterial prostatitis is an easily defined, diagnosed, and even managed disease. • Category II is characterized by evidence of prostatic inflammation (measured with white cells on expressed prostatic secretion, ejaculate, or urine voided after prostate massage) and prostatic pathogenic (read “uropathogenic”) bacteria in these specimens. In this category, patients have recurrent cystitis or lower urinary tract infections with uropathogenic bacteria. • Category III, now termed chronic pelvic pain syndrome or CPPS, encompasses the rest of the chronically symptomatic patients who have been diagnosed previously with chronic nonbacterial prostatitis and prostatodynia. These patients have complaints of genitourinary pain with variable voiding and sexual dysfunction. This classification does not presuppose a prostate etiology for their pain and voiding symptoms. However, it has been artificially sub- Prostatitis divided into IIIA and IIIB based on the presence or absence of inflammatory infiltrate in the prostate specific specimens (EPS, ejaculate, VB3) respectively (Figure). • Category IV recognizes that asymptomatic prostatic inflammation can coexist with BPH, prostate cancer, or in entirely healthy patients without symptoms. The clinical significance of Category IV prostatitis is unknown. These categories are described in Table 1. This classification system is going to prove useful in defining etiologic mechanisms. At the present time we are unsure of the etiology and pathophysiology of the chronic prostatitis syndromes. In addition, these artificial categories of II, IIIA, and IIIB have not been validated. Certainly, as far as culture results are concerned, we accept that acknowledged uropathogens14 such as gram-negative Enterobacteriaceae (Escherichia coli, Klebsiella, Pseudomonas) are likely an etiologic factor, but even this has never been proven. Probable uropathogens such as enterococci, possible uropathogens such as coagulase-negative Staphylococcus, Chlamydia, Ureoplasma, and anaerobes may also be involved in the infective process. Acknowledged nonuropathogens such as diphtheroids, lactobacilli, and Corynebacterium may be implicated (probably not). The role of cryptic nonculturable bacteria or even viruses is really unknown. There is also a school of thought that all bacteria in all chronic prostatitis syndromes are innocent bystanders and, even with eradication of the offending organisms, the symptoms remain. This all needs to be clarified before this classification system can be absolutely validated. For the rest of the patients, symptoms may be due to a spectrum of etiologic factors that include immunologic, chemical, neuromuscular, anatomic, and mechanical (ie, high pressure turbulent voiding ± intraprostatic ductal reflux) Figure. Microscopic appearance of expressed prostatic secretion (in this case, stained) from a patient with category IIIA chronic pelvic pain syndrome (inflammatory). Photomicrograph courtesy of A. J. Schaeffer, MD, Northwestern University, Chicago. abnormalities. Sophisticated immunologic, molecular biologic, neurophysiologic, and urodynamic studies will have to be done before we can define the etiologic mechanisms in this proposed classification system. For now, it is very useful to classify the patients, particularly the patients with chronic prostatitis, as having category II, IIIA, or IIIB disease, as it does allow us to rationalize a long-term management strategy (see Treatment). A Diagnostic Strategy—A Practical Approach. Clinical assessment: A patient presenting with category I prostatitis is easy to assess both at the time of initial presentation (suprapubic and perineal pain, severe tenderness of prostate gland, and generalized symptoms of fever, nausea, vomiting, etc), and it is simple to follow his symptoms as he improves. However, in the chronic prostatitis Table 1 Proposed NIH Classification of the Prostatitis Syndromes* Classification Category I Category II Category III Category IIIA Category IIIB Category IV Definition Acute bacterial infection (acute bacterial prostatitis) Infection and inflammation (chronic bacterial prostatitis) Chronic Pelvic Pain Syndrome (CPPS) Demonstrable prostatic inflammation but no infection No demonstrable prostatic inflammation or infection Asymptomatic inflammatory prostatitis (AIP) *See Table 2 for clinical differentiation of these categories. SUMMER 1999 REVIEWS IN UROLOGY 163 Prostatitis continued syndrome, categories II and III, this is more problematic. The patient presents with a long history of variable pain, urination, and sexual complaints, and each patient is somewhat different (although remarkably similar). In a similar clinical syndrome, lower urinary tract symptoms or BPH, a symptom score has been invaluable in assessing patients’ baseline symptoms and following their progress with various treatments. It has also proved useful in treatment trials comparing one treatment with another. These same types of symptom scores have and are being developed for prostatitis. The 2 presented (pages 166 and 167) represent a modification of the author’s previously validated Symptom Severity Index (SSI) and Symptom Frequency Questionnaire (SFQ).15 The NIH has recently finished a detailed study to define patients with prostatitis and develop a prostatitis symptoms index. The author, who was one of the investigators of the NIH Chronic Prostatitis Clinical Research Network (CPCRN), was able to retest the 20 questions from his SSI and SFQ and subsequently modified his original scores to be much better validated and clinically useful. The modified SSI is more sensitive to treatment changes, but the SFQ provides important clini- cal baseline information. Although the NIH Chronic Prostatitis Symptom Index will be the gold standard for clinical trials, this modified SSI/SFQ may prove to be a more practical way to take a more detailed prostatitis history and may be a more sensitive method to follow the severity and frequency of individual symptoms over time. Quality-of life assessment: Many instruments have been developed to quantitate the effect of disease on the patient’s quality of life, but none has yet been developed specifically for prostatitis. The author has found that the single quality-of-life question from the American Urological Association Symptom Index16 developed for BPH (AUA-SI) is very useful both at initial evaluation and in subsequent clinical follow-up. The question is familiar to most urologists: “If you were to spend the rest of your life with your [genitourinary] condition just the way it is now, how would you feel about that?” The index rates the patient’s response on a scale from 0 (Terrible) to 6 (Delighted). The NIH CPCRN is developing a specific Quality of Life/Impact Index for Prostatitis. Lower urinary tract localization studies: Unfortunately we do not have an ideal way to diagnose chron- Table 2 The Pre-and Post-Massage Test (PPMT)* NIH classification Category Category Category Category Category I II IIIA IIIB IV Bacteriuria Leukocytosis Pre-M + +/+/- Pre-M + +/+/- Post-M N/A + +/- Post-M N/A + + +/- *A practical screening test for chronic prostatitis: A urine specimen is collected before and after a vigorous prostate massage. The 2 specimens are sent for culture and microscopy of the centrifuged sediment. The presence of bacteria and leukocytosis in the post-M specimen can be used to differentiate the patient’s condition according to the NIH criteria. If the test is positive, some urologists may elect to proceed with the more definitive 4 glass (Meares-Stamey) test. Note that patients can have coexisting bacterial cystitis and prostatitis and, if differentiation is important, then the simple test can be repeated after 3 days of nitrofurantoin therapy. 164 REVIEWS IN UROLOGY SUMMER 1999 ic prostatitis and define patients with this condition. With all its limitations, we have to acknowledge that the Meares-Stamey 4 glass test3 is probably the best we have. However, for urologists in general clinical practice, this is not a practical test and, as mentioned in the previous section, has been largely abandoned. We have previously proposed the pre- and postmassage test (PPMT).17 This is based on the simple premise that, in most cases, urethritis is a simple clinical diagnosis associated with urethral discharge, dysuria, or itchiness or pain related to the urethra or penis and, if suspected, can be confirmed with a urethral swab culture. Urethritis, by itself, does not cause the complex of symptoms associated with the prostatitis syndromes. It is our opinion that an occult urethritis can coexist with prostatitis (probably pathogenically associated), and it would be a disservice to the patient— who has all the typical signs and symptoms of a chronic prostatitis syndrome—to reclassify him as having urethritis based on culture results of a VB1. Although it is generally accepted (especially by this author) that it would be most appropriate to culture and examine microscopically the EPS, this cannot be done by all physicians. Therefore, the initial voided urine after prostate massage (VB3 or post-M) represents the prostatic specimen. Leukocytosis and/or positive cultures in the post-M specimen compared with the pre-M specimen (VB2 or MSSU) can be used to categorize the patient’s condition as category II, IIIA, and IIIB (Table 2). In fact, a review of all available patients in the literature in whom MearesStamey tests were performed17 disclosed that eliminating the VB1 and EPS results and relying just on VB2 and VB3 made no difference in the final diagnosis. Our personal patient series17 also confirmed this finding. It may be that research will show examination and culture of the ejac- Prostatitis Table 3 Treatment of the Prostatitis Syndromes Category I Category II Category IIIA Category IIIB Category IV Initial IV antibiotics +/-Catheterization Antibiotics +/- Prostate massage Antibiotic trial +/- Prostate massage +/- α-blockers +/- Finasteride +/- Phytotherapy + Lifestyle changes Triple therapy α-blockers Muscle relaxants Analgesics +/- Tricyclic antidepressants +/- Biofeedback + Lifestyle changes No treatment indicated (unless ↑ PSA or infertile) Follow-up Oral antibiotics Follow-up Antibiotics (suppressive, prophylactic) Surgery? ulate, which is easier for urologists to collect, may be a valid surrogate for what is going on in the prostate gland. If physicians use the PPMT for a simple screen for prostatitis, some may want to follow up positive tests with the more rigorous and definitive 4 glass Meares-Stamey test. A Management Strategy—The Key to Treatment. “To cure if possible; but if cure is impossible, then ameliorate symptoms.” The practical approach to prostatitis outlined so far defines a working categorization of prostatitis, a practical diagnostic system to define patients and categorize their condition correctly, and then a way to tailor the management for that particular category.18 Except for almost all cases of category I prostatitis and some of category II, it must be realized both by the physician and the patient that cure is not always attainable and should not be the primary goal of therapy (Table 3). Amelioration of symptoms and improvement in quality of life are goals for which treatment should be employed. In the future, once the etiologic mechanisms have been discovered, analyzed, and evaluated, we may be able to provide a cure for the various subgroups of prostatitis, but for now, improvement of symptoms is our best expectation. • Category I: Category I has not been a problem for urologists to diagnose and manage. Following culture of the urine, collection of blood for culture, complete blood count, and physical examination (which usually discloses an enlarged, very boggy, and tender prostate gland), the patient is started on wide-spectrum, usually intravenous antibiotics. Most patients have significant obstructive voiding symptoms or are even in retention. A gently placed Foley catheter is indicated if this is the case. If there is difficulty or too much pain in inserting the catheter or it is too uncomfortable in situ, suprapubic cystotomy is advised. A trial of voiding can be undertaken within 24 to 36 hours. Unless the patient has developed a prostate abscess or the diagnosis is in question, the patient’s fever and generalized systemic symptoms improve in the first 36 to 48 hours. The catheter can be removed and the patient switched to oral antibiotics for 4 weeks. The optimal oral antibiotics are the fluoroquinolones, trimethoprim, or trimethoprim/sulfamethoxazole. • Category II: Patients in whom a Main Points • One of the problems in managing prostatitis can be physicians, whose attitudes may range from “prostatitis doesn’t exist” to “only surgery can cure it.” • The new NIH classification system for prostatitis can be useful in defining etiologic mechanisms. • In general, for the clinical urologist, the Meares-Stamey 4 glass test may not be practical. • The PPMT can be used to screen for prostatitis; in patients with positive results, the definitive Meares-Stamey 4 glass test can follow. • Cure is not always attainable and should not be the primary goal of therapy. • For patients with category II prostatitis, a course of 6-12 weeks of an appropriate antibiotic is recommended. • For patients with category IIIa prostatitis, a trial of antibiotics may be warranted. • In a patient with category IIIb prostatitis who has already failed a trial of antibiotics, triple therapy (α-blockers, analgesics, muscle relaxants) can be tried. • Interest in the diagnosis and management of chronic prostatitis is growing, and funding for research is following. • Objective prostatitis-specific symptom scores can be extremely useful in clinical practice. SUMMER 1999 REVIEWS IN UROLOGY 165 Prostatitis continued Symptom Severity Index (SSI) Please circle the number on each line that best describes your average symptoms on the days you have them over the last week. “0” means the symptom is absent and “10” means the symptom causes you problems (for example, pain) as bad as you can imagine. No problem Maximal severity 1. Pain or discomfort in the penis 0 1 2 3 4 5 6 7 8 9 10 2. Pain or discomfort in the area between the testicles & anus (perineum) 0 1 2 3 4 5 6 7 8 9 10 3. Pain or discomfort in the pubic or bladder area 0 1 2 3 4 5 6 7 8 9 10 4. Pain or discomfort during or after ejaculation 0 1 2 3 4 5 6 7 8 9 10 5. Pain or discomfort in the testicles 0 1 2 3 4 5 6 7 8 9 10 6. Pain or discomfort in the low back, upper leg, or groin area 0 1 2 3 4 5 6 7 8 9 10 7. Feeling of incomplete bladder emptying 0 after urinating 1 2 3 4 5 6 7 8 9 10 8. Urinating too often 0 1 2 3 4 5 6 7 8 9 10 9. Difficulty postponing urination 0 1 2 3 4 5 6 7 8 9 10 10. Pain or burning during urination 0 1 2 3 4 5 6 7 8 9 10 This simple-to-administer prostatitis specific questionnaire has been modified from the original SSI from data obtained from testing the original (or similar) questions during validation studies for the new NIH Chronic Prostatitis Symptom Index. The SSI (used together with the Symptom Frequency Questionnaire [SFQ]) has proven useful in both clinical studies and clinical practice. It has also proven more sensitive than the SFQ to follow patient response to therapy. 166 REVIEWS IN UROLOGY SUMMER 1999 Prostatitis Symptom Frequency Questionnaire (SFQ) For each symptom circle the one answer that best describes your situation. Symptoms Never 0 Rarely 1 Sometimes 2 Often 3 Usually 4 Always 5 Over the past week or so, how often have you had discomfort in the pubic or bladder area? 0 1 2 3 4 5 Over the past week or so, how often have you had pain or discomfort during or after ejaculation? 0 1 2 3 4 5 Over the past week or so, how often have you had pain or discomfort in the testicles? 0 1 2 3 4 5 Over the past week or so, how often have you had pain or discomfort in the penis? 0 1 2 3 4 5 Over the past week or so, how often have you had pain or discomfort in the area between the testicles and anus (perineum)? 0 1 2 3 4 5 Over the past week or so, how often have you felt that you are not emptying your bladder completely after urinating? 0 1 2 3 4 5 Over the past week or so, how often have you found yourself urinating too often? 0 1 2 3 4 5 Over the past week or so, how often have you had a painful or burning feeling during urination? Over the past week or so, about how time you go to bed at night? (√) 1 to 3 times a day 4 to 5 times a day 6 to 7 times a day many times do you urinate from the time you get up in the morning until the 8 to 9 times a day 10 to 11 times a day 12 or more times a day Over the past week or so, how many times did you most typically get up to urinate from the time you went to bed at night until the time you got up in the morning? (√) None 3 times 1 time 4 times 2 times 5 or more times This simple-to-administer prostatitis specific questionnaire (formatted very closely to the American Urological Association BPH Symptom Index) has been modified from the original Symptom Frequency Questionnaire (SFQ), from data obtained from testing the original (or similar) questions during the validation studies for the new NIH Chronic Prostatitis Symptom Index. The SFQ (used together with the Symptom Severity Index [SSI]) has proven useful in both clinical studies and clinical practice. Although not as sensitive as the SSI to measure effects of therapy, this questionnaire provides important baseline history information for the practicing clinician when first evaluating a difficult patient with chronic prostatitis. SUMMER 1999 REVIEWS IN UROLOGY 167 Prostatitis continued uropathogenic or presumed prostate pathogenic bacterium is isolated deserve a very long-term, full course of antibiotics. There has always been controversy concerning whether the patient should receive antibiotics for 4 weeks, 6 weeks, or 8 weeks. Our recent studies have shown that a 4week course of antibiotics is too short and does not predict the final 12week results.19 This has led us to conclude that in the rare case of a patient presenting with prostatitis in whose culture of prostatic secretions a uropathogen grows (perhaps 5% of total prostatitis cases), a 12-week course of appropriate antibiotics is indicated. The most appropriate antibiotics, based on pharmacokinetic data, are trimethoprim, trimethoprim/sulfamethoxazole, or a fluoro- from surgery. Patients should be willing to accept the morbidity of possible incontinence, impotence, and the fact that pain may continue despite removal of the infected prostate gland. • Category IIIA: Since we are not sure that some of the presumed prostate nonpathogens might be prostate pathogens, we have usually not cultured for Chlamydia and Mycoplasma. We often do not investigate whether previous antibiotic therapy may have masked subsequent localization. For category IIIA disease, a 6-week course of appropriate antibiotic therapy is indicated. This should cover not only the gram-negative rods but also gram-positive bacteria, Chlamydia, and Ureaplasma. A fluoroquinolone, such as ofloxacin, . . .it is the renewed interest in an old prostate disease by a new generation of urologic researchers that will change the face of prostatitis as we enter the new millennium. quinolone. Others have advocated erythromycin, the tetracyclines, and carbenicillin, but these really should be second-line antimicrobials for category II prostatitis. If the patient relapses, continuous suppressive antibiotics are indicated. If prostatitis recurs (with or without a different organism), low dose prophylaxis may be necessary. If the patient’s symptoms remain refractory, an attempt at repetitive prostatic massage (at least twice weekly) combined with antibiotics for a 6-week period may be beneficial in draining some of the obstructed prostatic ducts and allowing better antibiotic penetration. This historic and theoretical treatment has started to receive widespread general popularity again. Surgery is a very last resort and should be restricted to patients in whom the bacterium is identified in the prostate gland on biopsy. If a patient has prostatic calculi associated with bacteria, there is a greater chance that he may benefit 168 REVIEWS IN UROLOGY SUMMER 1999 or trimethoprim (or alternatively trimethoprim/sulfamethoxazole) and a tetracycline or erythromycin taken concurrently or sequentially may be indicated. If the response to antibiotics is positive, they can be continued according to the management strategy for category II prostatitis. If this approach is unsuccessful, repetitive prostate massage plus antibiotics for a further 6 weeks may be attempted. If the patient has obstructive voiding symptoms or mild obstruction is noted on uroflow studies (flow rates <20 mL/sec), the patient can receive a trial of α-blockers. Nonsteroidal antiinflammatory agents benefit some patients and should be tried. Phytotherapy and finasteride tend to benefit patients who have the larger, boggier prostates and very excessive leukocytosis in prostate secretions. Supportive therapies and lifestyle changes in terms of diet and aggravating factors (such as bike riding) are helpful. Usually with some combination of these treatments, patients’ symptoms are ameliorated. • Category IIIB: Most patients have already had a trial of antibiotics. Once the patient has failed antibiotics, antibiotic therapy is not recommended again unless the findings change. In such patients, we have advocated triple therapy, whether sequentially or concurrently. This therapeutic regimen consists of αblockers, analgesics, and muscle relaxants. In very severe, chronic, and refractory cases, we initiate highdose α-blockers (up to 20 mg terazosin), analgesics (for a short term, we would even advocate narcotic analgesia in severe cases), and muscle relaxants (we usually use diazepam, but others have used baclofen) at the same time. While the patient is receiving the first 2 weeks of this triple therapy, he should take time off from work. This triple therapy will usually alleviate his symptoms but cannot be continued indefinitely. If a narcotic analgesic is used, it will be reduced and discontinued by the end of the second week. The diazepam dose is decreased over the first month and finally discontinued, while the αblocker is continued for 3 to 6 months. Tricyclic antidepressants are useful in ameloriating symptoms in many patients with chronic pain syndromes, but they should not be used concurrently with the triple therapy regimen advocated above. If urodynamic studies disclose an obstructed voiding pattern with detrusor sphincter incoordination, biofeedback has been very helpful as well. Supportive therapies, including lifestyle changes and diet modification, have also proven helpful in some patients. Relaxation exercises, meditation, learning coping skills, as well as alternative medical therapies seem to benefit patients in this category. Many times, cure is not possible, and amelioration of symptoms, which sometimes has to be measured by symptom score analysis, is all that Prostatitis can be expected. • Category IV: Category IV prostatitis is by definition asymptomatic and the clinical significance of this inflammation is unknown. Management strategy is unnecessary in most cases. If associated with infertility or an elevated PSA, treatment may be indicated. Prospects for Improving the Perspectives in Prostatitis A number of exciting developments over the last several years are changing the realities of prostatitis research: The formation of a very strong patient advocacy group (the Prostatitis Foundation), a reappraisal of the epidemiologic scope of the problem, significant new funding initiatives by sponsoring agencies, and an awakening of interest by industry with the realization that prostatitis may truly be the largest, untapped disease in urology. But most of all, it is the renewed interest in an old prostate disease by a new generation of urologic researchers that will change the face of prostatitis as we enter the new millennium. The NIHsponsored CPCRN, a well-funded group of North American research centers, is developing a prostatitis symptom severity index, undertaking a formal longitudinal study of a cohort population of prostatitis patients, attempting to define the significance of leukocytosis and bacteria in urine and prostate specimens, and, finally, is initiating early treatment trials with the ultimate goal of being able to perform randomized controlled studies in the future. Other groups in the United States, Europe, and Asia have also committed themselves to the field of prostatitis research. This includes the recently organized International Chronic Prostatitis Network.20 Many are using sophisticated immunologic, microbiologic, and molecular biologic techniques to try to determine the etiology and pathogenesis of this disease. Others are exploring the neurophysiologic aspects of the disease, while other research sites are exploring new and innovative treatment options in a rigorous scientific manner. Industry, too, has become interested in prostatitis research, and it is not only funding basic research but also trying to determine if various available drugs may have significant benefit in various categories of prostate disease. While the initiatives described above are exciting, practicing urologists are treating patients today. If the urologist, who has become frustrated with this disease, decides to use the classification system, diagnostic plan, and therapeutic algorithm proposed in this review, he or she may find that the management of prostatitis will be just another enjoyable aspect of his urologic practice. ■ References 1. Nickel JC. Prostatitis: myths and realities. Urology. 1998;51:362-366. 2. Drach GW, Fair WR, Meares EM, et al. Classification of benign diseases associated with prostatic pain: prostatitis or prostatodynia? J Urol. 1978;120:266. 3. Meares EM, Stamey TA. Bacteriologic localization patterns in bacterial prostatitis and urethritis. Invest Urol. 1968;5:492-518. 4. Von Lackum WH. Clinical and experimental data on prostatic infection. J Urol. 1927;18:293-306. 5. Nickel AC. The bacteriology of chronic prostatitis and seminal vesiculitis and elective localization of the bacteria as isolated. J Urol. 1930;24:343-357. 6. Nickel JC. New concepts in the pathogenesis and treatment of prostatitis. Curr Opin Urol. 1992;2:37-43. 7. Collins MM, Stafford RS, O’Leary MP, et al. How common is prostatitis? A national survey of physician visits. J Urol. 1998;159:1224-1228. 8. Moon TD. Questionnaire survey of urologists and primary care physicians’ diagnostic and treatment practices for prostatitis. Urology. 1997;50:543-547. 9. Nickel JC, Nigro M, Voliquette L, et al. Diagnosis and treatment of prostatitis in Canada. Urology. 1998;52:797-802. 10. Roberts RO, Lieber MM, Bostwick DG, et al. A review of clinical and pathological prostatitis syndromes. Urology. 1997;49:809-821. 11. Moon TD, Hagen L, Heisey DM. Urinary symptomatology in younger men. Urology. 1997;50:700-703. 12. Wenninger K, Heiman JR, Rothman I, et al. Sickness impact of chronic nonbacterial prostatitis and its correlates. J Urol. 1996;155:965968. 13. National Institutes of Health Summary Statement. National Institute of Health/ National Institute of Diabetes and Digestive and Kidney Diseases Workship on Chronic Prostatitis. Executive Summary. Bethesda, Md: December 1995. 14. Nickel JC, Bruce AW, Reid G. Pathogenesis, diagnosis and treatment of the prostatitis syndromes. In: Krane RJ, Siroky MB, eds. Clinical Urology. Philadelphia, Pa: JB Lippincott; 1994:925-938. 15. Nickel JC, Sorensen R. Transurethral microwave thermotherapy for nonbacterial prostatitis: a randomized double-blind sham controlled study using new prostatitis specific assessment questionnaires. J Urol. 1996;155:1950-1954. 16. Barry MJ, Fowler FJJ, O’Leary MP, et al. The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. J Urol. 1992;148:15491557. 17. Nickel JC. The Pre and Post Massage Test (PPMT): a simple screen for prostatitis. Tech Urol. 1997;3:38-43. 18. Nickel JC. Effective office management of chronic prostatitis. Urol Clin North Am. 1998;25:677-684. 19. Nickel JC, Corcos J, Afridi SK, et al. Antibiotic therapy for chronic inflammatory (NIH Category II/IIIA) prostatitis. J Urol. 1998;159. Abstract. 20. National Institutes of Health Summary Statement. First National Institutes of Health International Prostatitis Collaborative Network Workshop on Prostatitis. Bethesda, Md: November 1998. SUMMER 1999 REVIEWS IN UROLOGY 169