EMERGING CONCEPTS IN PROSTATITIS

NEWS FROM THE 2000 AUA

J. Curtis Nickel MD
Professor of Urology
Queen’s University, Kingston, Canada

Introduction

Only a few short years ago, the number of prostatitis papers presented at the annual meeting of the American Urological Association could be easily counted on the fingers of one hand. An increased awareness of the importance and impact of this condition, increased peer reviewed funding and an awakening interest by industry has resulted in the an explosion of new studies in the field.

Epidemiology

Prostatititis is the most common urological diagnosis in men < 50 years old making up 8% of office visits to urologists (over 2 million office visits per year). The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) evaluates the 3 domains of the prostatitis experience (location, frequency and severity of pain, irritative and obstructive voiding symptoms, and impact/quality of life) in 3 quick and simple questions and has become the standard assessment tool in research studies and clinical practice. Downey et. al. from Canada (Abstract #97) reported one of the first population based studies to determine the prevalence of prostatitis-like symptoms among men at risk. Employing the NIH-CPSI, these investigators identified 9.7% of men in the community as having chronic prostatitis-like symptoms (7% had moderate to severe symptoms). Clinicians have always known that patients with prostatitis suffered consequences other than pain. McNaughton-Collins and her colleagues from the NIH Chronic Prostatitis Collaborative Research Network (Abstract #98) evaluated quality of life parameters in patients enrolled in the chronic prostatitis COHORT study using the medical outcome short form12 (SF-12) and the NIH Chronic Prostatitis Symptom Index. They noted that the quality of life (mental health impact) is profoundly impaired in men with chronic prostatitis. Optimal care of these patients requires particular attention to quality of life issues.

Etiology

We do not know what causes the findings and symptoms in in the 95% of men with a chronic prostatitis syndrome, but no cultured uropathogenic bacteria (chronic pelvic pain syndrome or CPPS; previously known as chronic nonbacterial prostatitis). Shoskes et. al. from California (Abstract #99) analyzed EPS and VB1 from 47 men with chronic pelvic pain syndrome (CPPS) by RT-PCR for bacterial signal using 16S rRNA. They noted that the presence of postive bacterial signal (10 times stronger signal in EPS compared to VB1) can help predict response to antimicrobial therapy. Shahed et. al. from California (Abstract #103) examined markers of tissue injury and injury response in EPS specimens from 100 CPPS patients. They concluded that gram positive bacteria may be pathogens based upon the injury response measured in the EPS. They also suggested that oxidative stress may be a key pathway in CPPS that can be successfully targeted with anti-oxidant therapy in patients with negative cultures. MacLennan et. al. from Cleveland (Abstract #108) examined the relationship between prostatitis and benign prostatic hyperplasia and prostate cancer by examining immunostained prostatectomy specimens. The data suggested that chronic prostatitis is associated with both BPH and prostate cancer but has a greater tendency to be associated with BPH without zonal prediliction. The role of prostatic inflammation in these two prostate diseases remains to be elucidated.

Diagnosis

The classic key to diagnosis has been the standard Meares-Stamey 4-glass test which differentiates symptomatic patients by the results of microscopy and culture of specific lower urinary tract specimens. Lee et. al. from Seattle (Abstract #101) evaluated 84 men with CPPS and 49 control patients with standard 4-glass urine tests and transperineal digitally guided prostate biopsies. They noted no significant difference between CPPS men and controls in the distribution and density of white blood cells in the EPS. Bacteria were found in prostate biopsy cultures of 46% of CPPS patients and 29% of control patients. There did not appear to be significant correlation between bacteria grown in post prostatic massage urine and the prostatic biopsy cultures. Patients with white blood cells in the EPS were more likely to have bacteria in prostate biopsy cultures than those with Category IIIB. This and other studies question the relevance of white blood cells and bacteria in the prostate gland and prostate specific specimens of patients with chronic prostatitis/chronic pelvic pain syndrome. Hochreiter et. al. from Chicago (Abstract #105) measured periodic cytokine levels in 18 men with CPPS and asymptomatic inflammatory prostatitis (Category IV). These authors concluded that serial monitoring of cytokine levels in EPS seems to be a reliable diagnostic tool which might be useful in the evaluation of patients with CPPS. It was interesting to note that when antibiotic treatment was given, in 93% of the cases, cytokine levels decreased regardless of changes in symptoms or inflammatory status.

Treatment

The most popular treatment employed by urologists for chronic prostatitis patients, regardless of culture results has been antibiotics. Other therapeutic modalities that have been suggested or are presently undergoing investigation include alpha blockers, phytotherapy, immune modulation, 5-alpha reductase inhibitors, COX-2 inhibitors, pentosan polysulfate, microwave heat therapy and various physical therapies. Nickel and the Canadian Prostatitis Research Group (Abstract #113) stratified 102 patients with chronic prostatitis/chronic pelvic pain syndrome into Category II, Category IIIA and Category IIIB based on leukocyte, culture and immunologic status. Over 50% of patients had a moderate to marked improvement employing validated prostatitis symptom indices, however culture, leukocyte or immune status of prostate specific specimens did not predict response to antibiotics. The perceived beneficial effects of antibiotics in all categories needs to be evaluated in a randomized placebo controlled trial. Clemens et. al. (Abstract #114) from Chicago evaluated the results of a 12 week program of biofeedback directed to pelvic floor re-education and bladder training in 19 patients with CPPS. This preliminary study suggested that a formalized program of neuromuscular re-education of the pelvic floor muscles together with interval bladder training can provide significant and durable improvement in pain, urgency and frequency in patients with CPPS.

Conclusion

The field of prostatitis is changing. The research presented at this year’s 2000 AUA has signalled a major shift from the the standard approach of previous decades of evaluating various antibiotics for chronic bacterial prostatitis. It appears that the major thrust of research in this decade will be directed towards an understanding of the condition in the many men without positive cultures (chronic pelvic pain syndrome) and an evidence-based approach to therapy.