Links probed between prostate volume, cancer prediction

Atlanta-Results from the Prostate Cancer Prevention Trial (PCPT) showing treatment with the type 2-specific 5-alpha-reductase inhibitor finasteride (Proscar) reduced the incidence of prostate cancer, but was associated with increased detection of high-grade cancers has prompted additional research on the association among prostate cancer detection, cancer grade, and prostate volume.

"We hypothesized that the results of the PCPT reflected a sampling artifact related to the effect of finasteride in reducing prostate size, and that there was no biologic rationale for an association between smaller prostate size and higher-grade cancer. Instead, we found in our cohort of men not treated with a 5-alpha-reductase inhibitor that the pathological features were more favorable in patients with larger glands relative to those with smaller-volume prostates," said Alberto Briganti, MD, department of urology, Vita-Salute University, Milan, Italy.

In univariate analysis with prostates divided into quartiles according to volume, significant associations among increasing prostate size and decreasing prevalence of high-grade cancer, extracapsular extension, and seminal vesicle invasion were seen. All three tumor-related variables investigated (biopsy Gleason score, PSA, and clinical stage) also were significant predictors of pathologic outcomes in univariate analysis.

Outcomes consistent across studies

Dr. Briganti also noted that the results of this study are consistent with those recently reported by Freedland et al (J Clin Oncol 2005; 23:7546-54). Using multivariate analytical techniques, investigators in that published study also determined that smaller prostate volume was a significant predictor of high-grade prostate cancer at pathologic assessment.

"There is a growing body of literature showing that patients with smaller glands have a greater chance of being affected by more advanced prostate cancer," Dr. Briganti said. "Thus, our results seem to show that in the PCPT trial, the increased rate of high-grade prostate cancer in small glands might have been gland-volume related."

In another study, researchers from the University of Texas at Dallas and GlaxoSmithKline, Research Triangle Park, NC, used mathematical modeling to explore the extent to which the findings in the PCPT could be explained by the effect of finasteride on prostate volume. A model was developed by Robert J. Serfling, PhD, professor of mathematical sciences at the University of Texas, in partnership with Roger S. Rittmaster, MD, urology clinical development, GlaxoSmithKline, and several other collaborators.