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THE PROBLEM WITH PROSTATITIS. WHAT DO WE KNOW? WHAT DO WE NEED TO KNOW?
0022-5347/04/2172-0432/0 THE JOURNAL OF UROLOGY® Copyright © 2004 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 172, 432– 433, August 2004 Printed in U.S.A.
DOI: 10.1097/01.ju.0000132864.57677.91
THE PROBLEM WITH PROSTATITIS. WHAT DO WE KNOW? WHAT DO WE NEED TO KNOW? The problem with prostatitis is that we lack data driven recommendations for managing it. This issue of The Journal contains 3 articles addressing different aspects of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), the most common and frustrating syndrome. What can the interested reader learn from these articles? EMPIRICAL THERAPY
Nickel et al (page 551) have moved to a completely empirical approach emphasizing treatment trials in their tertiary referral population. They outline their ongoing optimism for new therapies and their increasing frustration with every single treatment they have tried. The 100 cases referred to their special prostatitis research clinic were “difficult” by definition. The average patient had symptoms for more than 6 years, and previous treatments had failed, including antibiotics (96%), anti-inflammatory (46%), phytotherapy (33%), zinc (30%), ␣ blockade (22%) and many others. After screening to exclude other conditions, patients were treated using “lifestyle supportive therapies” plus a variety of additional therapies, including antibiotics, ␣ blockade, antiinflammatory therapy, prostate massage, other physical therapy, finasteride, pentosan polysulfate and phytotherapy (quercetin). Many recommendations were based on previous reports from this group describing encouraging treatments to improve CP/CPPS, such as transurethral microwave thermotherapy, transurethral radio frequency hot balloon thermal therapy, percutaneous peripheral nerve stimulation, acupuncture, repetitive prostatic massage, ␣-blockers (alfuzosin), pentosan polysulfate, antibiotics (levofloxacin), finasteride and anti-inflammatory (rofecoxib) therapy. Patients who responded were continued on therapy, and new treatments were instituted for those who failed. In this nonblinded, uncontrolled series 71% of patients had better National Institutes of Health (NIH) chronic prostatitis symptom index (CPSI) scores after 1 year, although a “clinically perceptible (greater than 25%) improvement” was noted in only a third. “Surprisingly, this degree of improvement has been noted. . .in placebo arms of multiple randomized placebo controlled trials. . ..” With this single clinical series the authors conclude that their previous clinical trials were overly optimistic. Currently, these investigators recommend multimodal therapy as the, “superior. . .strategy,” especially for patients in whom initial therapy has failed. Multimodal regimens for other diseases are based on demonstrated activity of single agents. Examples include chemotherapy regimens, treatment of infections such as tuberculosis or HIV and combination therapy for benign prostatic hyperplasia. It will be interesting to evaluate the results of this innovative approach to multimodal therapy. POST-EJACULATORY PAIN
Shoskes et al (page 542) emphasize the importance of postejaculatory pain in the NIH Chronic Prostatitis Cohort study. In this tertiary referral population post-ejaculatory pain was associated with worse symptoms and a worse prognosis. Of 486 participants 26% regularly suffered from postejaculatory pain, 50% had it intermittently and 26% never experienced it. Modified NIH-CPSI scores increased from the subgroup in which post-ejaculatory pain was absent to the subgroup in which post-ejaculatory pain was present consistently. Ejaculatory pain was associated with younger age,
worse mental and physical quality of life, living alone and having a lower income. Significant improvement in total NIH-CPSI score (greater than 50%, “which correlates well with patient perception,” compared to greater than 25% in the study by Nickel et al) was less likely in patients with post-ejaculatory pain at all visits (12%) than among those who never reported post-ejaculatory pain (22%, p ⬍0.05). The authors suggest that ejaculatory pain may reflect a specific etiology, a marker of greater CP/CPPS severity, a generalized increased sensitivity to pain or another mechanism. Post-ejaculatory pain may provide a stratification tool in clinical trials because patients with ejaculatory pain and CP/CPPS have worse symptoms and poorer outcomes. PROGNOSIS
Turner et al (page 538) recruited patients from Group Health Cooperative, a large staff model health maintenance organization. The 286 participants did not visit physicians within the previous year and had no documentation of other conditions that might cause pelvic pain. This was for a first episode for 100 men (35%). The population was largely white (87%) and well educated (51% college graduates). Participants were interviewed by telephone and medical records were reviewed in 86% of cases. This was a “treated natural history” study with antibiotics (56%), anti-inflammatory therapy (19%), opiates (4%), phenazopyridine hydrochloride (2%) and ␣ blockers (2%). Adherence to therapy was not evaluated. Half of the participants made no further visits after the index visit. On average, patients improved substantially from baseline to 3 months, improved modestly from 3 to 6 months, and then remained unchanged or worsened slightly from 6 to 12 months. Patients whose initial visits were for recurrent episodes had worse symptoms. Baseline NIH-CPSI score and first versus recurrent episode status but not age, symptom duration, race, education or presence of urinary symptoms predicted symptoms at the 12-month followup. Although symptoms improved with time on average, more than a third with initial episodes and more than half of those with recurrent episodes at the index visit reported persistent symptoms 1 year later. The authors reasonably emphasize the need to study prostatitis in settings other than tertiary referral centers. Treatment efficacy may differ for patients with milder symptoms of recent onset versus patients with long-standing severe symptoms. They also stress the need to identify treatments that prevent acute problems from becoming chronic. BOTTOM LINE
What do we know? Each of these 3 articles has a major message and each emphasizes at least 1 significant issue. The study by Nickel et al illustrates the need to consider treatment results in light of the high placebo response rate. In other words, future clinical trials should be randomized, placebo controlled and double-blind. Shoskes et al emphasize post-ejaculatory pain as a potential marker for severe CP/ CPPS with a worse prognosis. This finding is consistent with other data suggesting that CP/CPPS is not a single, homogeneous disorder. Patients may suffer various pathophysiological processes that require individualized therapy. Turner et al suggest that less selected patients respond better to treatment than highly selected, tertiary care referral populations.
432
PROBLEM WITH PROSTATITIS
What do we need to know? The study by Nickel et al illustrates the critical need for treatments that can be proven effective in properly designed studies and confirmed in clinical practice. Shoskes et al emphasize the need for better clinical or laboratory criteria that can be used to select individualized diagnostic and treatment protocols. Turner et al stress the need for strategies to prevent prostatitis in the first place and limit the potential for acute prostatitis to
433
progress to CP/CPPS. Resolving these issues will go a long way to solving the problem of prostatitis. John N. Krieger Department of Urology University of Washington Seattle, Washington
Vol. 172, 432– 433, August 2004 Printed in U.S.A.
DOI: 10.1097/01.ju.0000132864.57677.91
THE PROBLEM WITH PROSTATITIS. WHAT DO WE KNOW? WHAT DO WE NEED TO KNOW? The problem with prostatitis is that we lack data driven recommendations for managing it. This issue of The Journal contains 3 articles addressing different aspects of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), the most common and frustrating syndrome. What can the interested reader learn from these articles? EMPIRICAL THERAPY
Nickel et al (page 551) have moved to a completely empirical approach emphasizing treatment trials in their tertiary referral population. They outline their ongoing optimism for new therapies and their increasing frustration with every single treatment they have tried. The 100 cases referred to their special prostatitis research clinic were “difficult” by definition. The average patient had symptoms for more than 6 years, and previous treatments had failed, including antibiotics (96%), anti-inflammatory (46%), phytotherapy (33%), zinc (30%), ␣ blockade (22%) and many others. After screening to exclude other conditions, patients were treated using “lifestyle supportive therapies” plus a variety of additional therapies, including antibiotics, ␣ blockade, antiinflammatory therapy, prostate massage, other physical therapy, finasteride, pentosan polysulfate and phytotherapy (quercetin). Many recommendations were based on previous reports from this group describing encouraging treatments to improve CP/CPPS, such as transurethral microwave thermotherapy, transurethral radio frequency hot balloon thermal therapy, percutaneous peripheral nerve stimulation, acupuncture, repetitive prostatic massage, ␣-blockers (alfuzosin), pentosan polysulfate, antibiotics (levofloxacin), finasteride and anti-inflammatory (rofecoxib) therapy. Patients who responded were continued on therapy, and new treatments were instituted for those who failed. In this nonblinded, uncontrolled series 71% of patients had better National Institutes of Health (NIH) chronic prostatitis symptom index (CPSI) scores after 1 year, although a “clinically perceptible (greater than 25%) improvement” was noted in only a third. “Surprisingly, this degree of improvement has been noted. . .in placebo arms of multiple randomized placebo controlled trials. . ..” With this single clinical series the authors conclude that their previous clinical trials were overly optimistic. Currently, these investigators recommend multimodal therapy as the, “superior. . .strategy,” especially for patients in whom initial therapy has failed. Multimodal regimens for other diseases are based on demonstrated activity of single agents. Examples include chemotherapy regimens, treatment of infections such as tuberculosis or HIV and combination therapy for benign prostatic hyperplasia. It will be interesting to evaluate the results of this innovative approach to multimodal therapy. POST-EJACULATORY PAIN
Shoskes et al (page 542) emphasize the importance of postejaculatory pain in the NIH Chronic Prostatitis Cohort study. In this tertiary referral population post-ejaculatory pain was associated with worse symptoms and a worse prognosis. Of 486 participants 26% regularly suffered from postejaculatory pain, 50% had it intermittently and 26% never experienced it. Modified NIH-CPSI scores increased from the subgroup in which post-ejaculatory pain was absent to the subgroup in which post-ejaculatory pain was present consistently. Ejaculatory pain was associated with younger age,
worse mental and physical quality of life, living alone and having a lower income. Significant improvement in total NIH-CPSI score (greater than 50%, “which correlates well with patient perception,” compared to greater than 25% in the study by Nickel et al) was less likely in patients with post-ejaculatory pain at all visits (12%) than among those who never reported post-ejaculatory pain (22%, p ⬍0.05). The authors suggest that ejaculatory pain may reflect a specific etiology, a marker of greater CP/CPPS severity, a generalized increased sensitivity to pain or another mechanism. Post-ejaculatory pain may provide a stratification tool in clinical trials because patients with ejaculatory pain and CP/CPPS have worse symptoms and poorer outcomes. PROGNOSIS
Turner et al (page 538) recruited patients from Group Health Cooperative, a large staff model health maintenance organization. The 286 participants did not visit physicians within the previous year and had no documentation of other conditions that might cause pelvic pain. This was for a first episode for 100 men (35%). The population was largely white (87%) and well educated (51% college graduates). Participants were interviewed by telephone and medical records were reviewed in 86% of cases. This was a “treated natural history” study with antibiotics (56%), anti-inflammatory therapy (19%), opiates (4%), phenazopyridine hydrochloride (2%) and ␣ blockers (2%). Adherence to therapy was not evaluated. Half of the participants made no further visits after the index visit. On average, patients improved substantially from baseline to 3 months, improved modestly from 3 to 6 months, and then remained unchanged or worsened slightly from 6 to 12 months. Patients whose initial visits were for recurrent episodes had worse symptoms. Baseline NIH-CPSI score and first versus recurrent episode status but not age, symptom duration, race, education or presence of urinary symptoms predicted symptoms at the 12-month followup. Although symptoms improved with time on average, more than a third with initial episodes and more than half of those with recurrent episodes at the index visit reported persistent symptoms 1 year later. The authors reasonably emphasize the need to study prostatitis in settings other than tertiary referral centers. Treatment efficacy may differ for patients with milder symptoms of recent onset versus patients with long-standing severe symptoms. They also stress the need to identify treatments that prevent acute problems from becoming chronic. BOTTOM LINE
What do we know? Each of these 3 articles has a major message and each emphasizes at least 1 significant issue. The study by Nickel et al illustrates the need to consider treatment results in light of the high placebo response rate. In other words, future clinical trials should be randomized, placebo controlled and double-blind. Shoskes et al emphasize post-ejaculatory pain as a potential marker for severe CP/ CPPS with a worse prognosis. This finding is consistent with other data suggesting that CP/CPPS is not a single, homogeneous disorder. Patients may suffer various pathophysiological processes that require individualized therapy. Turner et al suggest that less selected patients respond better to treatment than highly selected, tertiary care referral populations.
432
PROBLEM WITH PROSTATITIS
What do we need to know? The study by Nickel et al illustrates the critical need for treatments that can be proven effective in properly designed studies and confirmed in clinical practice. Shoskes et al emphasize the need for better clinical or laboratory criteria that can be used to select individualized diagnostic and treatment protocols. Turner et al stress the need for strategies to prevent prostatitis in the first place and limit the potential for acute prostatitis to
433
progress to CP/CPPS. Resolving these issues will go a long way to solving the problem of prostatitis. John N. Krieger Department of Urology University of Washington Seattle, Washington