While the prostate cancer prevention trial (PCPT) demonstrated that the use of finasteride was associated with a 25% decreased risk of developing prostate cancer, its results have not been widely adopted because a higher proportion of patients in the finasteride group were diagnosed with high grade prostate cancer.

Several potential explanations have been proposed for the association between finasteride and high grade disease including: (1) finasteride results in a histologic artifact causing an over-diagnosis of high grade disease. (2) finasteride results in prostate size reduction which may lead to over-sampling of high grade disease, and (3) finasteride increases the performance characteristics of PSA, thus increasing detection of prostate cancers of all grades in for-cause biopsies. The main finding of the PCPT supporting points (2) and (3) was that the incidence of high grade cancer did not increase as the length of treatment with finasteride increased. In other words, the increased hazard ratio for high grade cancers appeared early in the study and did not increase with time.

In the August 16th issue of the JNCI, Thompson and colleagues present compelling data from the PCPT supporting the hypothesis that finasteride increases the performance characteristics of PSA as a screening tool. Using data from 9,691 men in the PCPT, the authors assessed the effect of finasteride on the sensitivity and area under the receiver operating characteristics curve (AUC) of PSA for prostate cancer detection. Interestingly, the sensitivity of PSA in the finasteride arm was significantly higher than the placebo arm at all PSA levels after adjusting for specificity. The AUC of PSA in men taking finasteride was higher for detecting all cancers (0.747 vs. 0.681, P < 0.001) and for detecting high grade disease (0.838 vs. 0.781, P = 0.003).

This study has shown, for the first time, that taking a drug may increase the performance characteristics of serum PSA for detecting prostate cancer (particularly high grade tumors). These data may in part explain the increased detection of high grade tumors in the PCPT and raise additional questions regarding the potential use of finasteride in maximizing the efficacy of serum PSA for early prostate cancer detection.

By Ricardo S?nchez-Ortiz, MD

Link Here.
Journal of the National Cancer Institute, Vol. 98, No. 16, 1128-1133, August 16, 2006
Ian M. Thompson, Chen Chi, Donna Pauler Ankerst, Phyllis J. Goodman, Catherine M. Tangen, Scott M. Lippman, M. Scott Lucia, Howard L. Parnes, Charles A. Coltman, Jr.

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