Urologic Diseases Research Updates
Winter 2009

NIDDK Hosts Prostate Workshop

Prostate problems, though long considered an inevitable part of aging for men, may be preventable, according to scientists who participated in a workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

The workshop’s goals were to review the state of the science around benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS), identify data gaps, and prioritize future research. Central to the workshop was identifying modifiable risk factors—those factors that can be controlled or changed, such as diet and smoking.

BPH is an enlargement of the prostate—a gland below the bladder that surrounds the urethra—a common condition affecting about 50 percent of men in their 50s. When enlarged, the prostate can restrict urine flow from the bladder.

LUTS are the symptoms thought to be related to BPH; however, LUTS are not exclusive to BPH or men. LUTS in men include frequent urination, difficulty starting or maintaining a urine stream, the inability to completely empty the bladder, the need to get up at night to urinate, dribbling, and the tendency to retain urine in the bladder. Between 26 and 46 percent of men ages 40 to 79 have moderate to severe LUTS.

“Can we stop the progression of BPH/LUTS? Or, even more importantly, can we prevent the disease?” Robert A. Star, M.D., director of the NIDDK’s Division of Kidney, Urologic, and Hematologic Diseases asked the assembled group of epidemiologists, basic scientists, and urologists.

Defining BPH/LUTS

Key to identifying modifiable risk factors is defining the problem, but according to John Wei, M.D., M.S., associate professor of urology at the University of Michigan, “there are as many definitions of LUTS as there are clinical trials,” making comparisons between studies difficult.

A universal definition of LUTS is lacking because men can develop LUTS from a variety of causes related or unrelated to the prostate. And while some men have severe LUTS and relatively minor BPH, others have significant prostate enlargement but are not bothered by symptoms. These observations suggest the existence of multiple LUTS subtypes with diverse etiologies and corresponding risk factors.

Biomarkers and Endpoints

Surrogate biomarkers and measurable endpoints are needed to characterize LUTS subtypes, according to Elizabeth Platz, Sc.D., M.P.H., associate professor of epidemiology at the Johns Hopkins University Bloomberg School of Public Health.

Prostate volume, although widely used in clinical research, has fallen out of favor as a surrogate biomarker for LUTS. “Prostate volume simply establishes a man has a prostate,” said Wei, suggesting size has only limited bearing on symptoms or disease progression.

Self-reported measures, such as the International Prostate Symptom Score—essentially a patient’s rating of symptom severity and quality of life—would provide excellent and inexpensive surrogate biomarkers and endpoints for LUTS cohort studies, according to Alan R. Kristal, Dr.P.H., of the Fred Hutchinson Cancer Research Center.

Several promising serum biomarkers were recognized at the workshop, including the protein JM-27, which was shown by the NIDDK-funded Prostatic Samples Analysis (MPSA) Consortium to be higher in men with symptomatic BPH than in men with asymptomatic BPH. MPSA is an outgrowth of the Medical Therapy of Prostatic Symptoms clinical trial, which was originally designed to test the effectiveness of the drugs finasteride and doxazosin at stopping or slowing the progression of BPH.

Future Studies

During facilitated discussions, workshop participants identified knowledge gaps and devised future studies. Most agreed that leveraging existing clinical studies would be the most economic and fastest way to characterize LUTS subtypes.

“Seventy-five percent of our questions can be answered by existing cohorts,” surmised Steven Jacobsen, M.D., Ph.D., director of research at the Southern California Kaiser Permanente Medical Group. Such an approach would rely on data and specimens from other studies, related or unrelated to BPH/LUTS, or “piggybacking” with ongoing or new studies.

Smaller proof-of-concept studies would complement larger epidemiological studies, Platz suggested, which would test specific interventions such as a case-control trial evaluating the effect of diet and exercise on slowing LUTS progression.

A formal list of recommendations for studying modifiable risk factors for BPH/LUTS is forthcoming.

Publications about prostate problems are available from the National Kidney and Urologic Diseases Information Clearinghouse at www.kidney.niddk.nih.gov/kudiseases/a-z.asp.

NIH Publication No. 09–5743
March 2009

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