Prostate Disease Begs Understanding
Vol. 286 No. 4, July 25, 2001 Brian Vastag, Washington.
Sometimes a diagnosis is a dead end, a label with little guidance. So it goes with chronic prostatitis also called chronic pelvic pain syndrome, the newer term which prompts some 2 million office visits in the United States each year (J Urol. 1998;159:1224-1228).
A catch-all term to describe an array of symptoms that include pain in various places, urinary problems, and sexual dysfunction, "prostatitis" reflects a lack of knowledge regarding origins and effective treatments that led urologist Thomas Stamey, MD, to call the diagnosis a "wastebasket of clinical ignorance."
To illustrate the point, Leroy Nyberg, MD, PhD, head of urology research at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), sketched a typical scenario: a man complains of prostate symptoms and, after ruling out obvious bacterial infections, urethral strictures, bladder disorders, and cancer, the physician shrugs his shoulders, calls it chronic nonbacterial prostatitis, and prescribes an antibiotic like ciprofloxacin or an -blocker like tamsulosin although neither has ever been tested against the disease.
That scene is slowly changing. This summer, the NIDDK will begin the first placebo-controlled clinical trial of antibiotics and -blockers, to finally determine whether the standard treatments provide any relief. The study comes 6 years after the Prostatitis Foundation patient group convinced Congress to prod the National Institutes of Health to furnish some funding. "Because it isn't a deadly disease, it required a lot of momentum from the outside to get us going," said Nyberg."But now we've realized the impact of the disease". To back his words, Nyberg oversees some $2 million in annual grants aimed at probing the most basic questions: what is prostatitis, who gets it and will anything treat it?
Answers are appearing, some from small treatment studies and others from the NIDDK's Chronic Prostatitis Collaborative Research Network, six centers tracking the natural history of the condition in a cohort of 450 patients. For starters, researchers want to define the breadth of the problem. A small study from Ontario reported that 10% of men in the general population had symptoms of chronic pelvic pain syndrome (J Urol. 2001;165:842-845). Another study from Finland reported a prevalence nearing 15% (BJU Int. 2000;86:443-448), and other reports suggest that up to half of all men will experience some type of prostatitis during their lifetime (Eur Urol. 1992;22:14). If those figures hold in a larger epidemiological study planned by the NIDDK, chronic pelvic pain syndrome would be among the most common ailments in men, a fact that makes the dearth of understanding all the more disturbing.
After surveying this sorry state, the NIDDK brought together prostatitis researchers there were only a handful at the time at a 1995 conference. The participants immediately realized that de facto clinical definitions held little meaning and proposed a new system of nomenclature. They settled on three categories: acute and chronic bacterial prostatitis (with documented infections) and chronic pelvic pain syndrome. While the first two generally respond to antibiotics, they account for just 5% to 10% of cases. Since then, a handful of new ideas have been getting attention and, finally, the scrutiny of rigorous testing. While some researchers maintain that difficult-to-find bacterial infections are to blame, others document evidence of autoimmune activity. A third camp holds that chronic tension in the pelvic floor muscles, not the prostate itself, accounts for the problem. And some think that all three processes could be at play.
Shoskes and other researchers also report evidence of chronic inflammation or autoimmunity in patients with no evidence of infection. Shoskes became intrigued with the idea when he noticed parallels between kidney transplant rejection and chronic prostatitis. "In both cases you have some type of initial injury or event . . . and then weeks or months later you still have this progressive inflammatory condition."
In 1999, Shoskes published a small study with the dietary supplement quercetin, a bioflavonoid antioxidant and anti-inflammatory agent. After taking 500 mg of the supplement twice daily for a month, two thirds of men in the treatment group (and only 20% in the control group) reported a 25% or greater improvement in symptoms (Urology. 1999;54:960-963). But the study was small (30 patients) and remains to be replicated. While quercetin can be bought off the shelf, the agent under study by Alexander and other urologists costs more than $10 000 per year. Called etanercept (Enbrel, Immunex Corp, Seattle), the drug binds to and sops up excess molecules of tumor necrosis factor. Approved by the US Food and Drug Administration in 1998 for treatment of rheumatoid arthritis the most common autoimmune disease in the country the drug reduces joint pain in most patients with that disease. Data from the etanercept prostatitis trial should be available next year.
Ultimately, all or none of these ideas may lead to proven, effective treatments. "Right now, the evidence for any etiology is minimal," said the NIDDK's Nyberg. "It's a level playing field, and there are a lot of ideas around." While the new ideas shake out, some of the old especially that antibiotics and -blockers are helpful may fall into disfavor after the NIDDK clinical trial. Maryland's Alexander, for one, thinks that the results will pick prostatitis out of the clinical trash bin. "In the next year or two, the data from the [NIDDK] cohort study are going to debunk a lot of the myths about this problem," he said. "And it's going to be clear that the assumptions are wrong and that we need to start all over again."
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