PCRI News – The Finasteride Controversy

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The Finasteride Controversy
Monday, February 16, 2004

Last summer, a team of 16 researchers reported on the seven-year Prostate Cancer Prevention Trial study that followed almost 19,000 men. The article, entitled “The Influence of Finasteride on the Development of Prostate Cancer”, was published in the July 17, 2003 issue of The New England Journal of Medicine.

The report made quite a stir in the prostate cancer community because of two fundamental findings reported as follows. “Seven years of finasteride treatment resulted in a 24.8 percent reduction in the prevalence of prostate cancer [as compared to a placebo group] during that period. There was a reduction in relative risk among men who underwent a prostate biopsy before seven years and among men who underwent biopsy at the end of the study. The risk reductions were similar in subgroups defined according to age, race or ethnic group, family history of prostate cancer, and stratum of PSA level at randomization.”

The second finding reported was that “high-grade disease [as defined by Gleason Scores of 7, 8, 9, or 10] was noted in 6.4 percent of the men in the finasteride group, as compared with 5.1 percent of those in the placebo group. A difference in the rate of high-grade disease was seen within the first year of the study.

One possible explanation for this difference is a grading bias: histologic changes that mimic those of high-grade disease are caused by androgen-deprivation therapy.” And five different published papers were cited as sources for this explanation.

However, in that same issue, Peter D. Scardino, M.D. published an editorial concerning the PCPT results. Apparently not too impressed with a 25% reduction in the prevalence of PC, he concentrated on the apparent increase in incidence of high-grade cancers to 6.4 percent of the finasteride group (as compared to 5.1 percent of the placebo group). Ignoring the possible grading-bias and other explanations offered by the study authors, he concentrated on the possible dangers of highgrade PC, saying, “Cancers with a Gleason Score of 7 to 10 contain poorly differentiated components that are known to behave aggressively.

The risk of death due to prostate cancer within 15 years of diagnosis among men with such cancers that are managed conservatively ranges from 42 percent to 87 percent, depending on age and Gleason grade at diagnosis, according to one study…[t]he study results suggest that finasteride may accelerate the growth of high-grade cancers, which may pose a threat to life and health if they are not treated successfully.”

There is little question that high-grade cancer is a serious situation, pathologists would agree, but pathologists question whether Gleason grading should be used to assess PC aggressiveness after ADT treatment—and Gleason himself agrees. According to pathologist David Bostwick, M.D., “treated cancer has a significantly higher architectural (Gleason) grade, lower nuclear grade, and smaller nuclear diameter than untreated controls, thus creating the potential for grading bias. I’m convinced that this is what occurred in the PCPT study.”

The accompanying article Does Finasteride Alter the Pathology of the Prostate and Cancer Grading? by Dr. Bostwick provides the scientific basis for this conviction.

Reproduced from

PCRI Insights vol.7, no. 1