Tumor shrinkage explains excess high-grade cancers in PCPT

Tumor shrinkage explains excess high-grade cancers in PCPT

Two new analyses of the Prostate Cancer Prevention Trial find it unlikely that finasteride induces high-grade tumors. Both reports conclude that the increased rate of high-grade prostate cancer found in the finasteride arm stems from the drug's ability to shrink the prostate, making it easier to detect the more aggressive tumors at biopsy (J Natl Cancer Instit 99:1366-1374; 1375-1383, 2007).

PCPT, which randomized 18,882 men at risk of prostate cancer to daily finasteride or placebo, showed a 24.8% relative reduction in the 7-year prevalence of prostate cancer among the finasteride-treated patients but also a 25.5% increase in the prevalence of tumors with Gleason scores of 7 to 10 (6.4% vs 5.1%).

M. Scott Lucia, MD, of the University of Colorado, and his SWOG colleagues compared tissue samples from biopsies and from prostates removed from men in the PCPT who had Gleason scores of 7 to 10. The finasteride patients had lower prostate volume and more high-grade cancers at biopsy (42.7% vs 25.4% for placebo), but at prostatectomy, the difference was not significant (46.4% vs 38.6%). They found that biopsy accurately detected high-grade cancer only 50% of the time in the placebo group but 70% of the time in the finasteride group.

Yael C. Cohen, PhD, of Gamida Cell Ltd, Jerusalem, and his colleagues developed a logistic model using the PCPT placebo patients and applied it to the finasteride patients. As in Lucia's study, median prostate volume was 25% lower in the finasteride group vs placebo. The model showed that the likelihood of detecting a high-grade cancer decreased as prostate volume increased. Based on this model, 239 high-grade prostate cancers were predicted in the finasteride group, whereas 243 were observed, a nonsignificant difference. "If our conclusion that finasteride accelerates the detection of high-grade cancer yet may not promote its development is correct, then the implications regarding the clinical impact of this drug are quite favorable," the authors concluded. "The occurrence of lower grade tumors of questionable clinical significance would be reduced, and the early detection of more serious tumors would be enhanced."

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