High-grade prostate cancer and finasteride

Prostate cancer is the most common neoplasm in men. Encouraging results are emerging in prostate cancer risk reduction with 5 alpha-reductase (5AR) inhibitors. The Prostate Cancer Prevention Trial (PCPT) showed that prostate cancer risk is reduced by finasteride. However, there was an increase in the incidence of high-grade prostate cancer with finasteride treatment vs placebo. The number of cases should have increased during the study in the finasteride group with the length of exposure to the drug. But, in fact the ratio between the two groups was lower during the fourth year. This therefore favours the hypothesis of a bias in the results. There are many hypotheses to explain the increase in the prevalence of high-grade tumours with finasteride therapy. The effects of finasteride on prostate volume rather than on the tumour's morphology and a selective inhibition of low-grade cancers may have contributed to the increase the number of high-grade cancers with finasteride in the PCPT. Despite the current trend to explain the increase of high-grade tumours with finasteride therapy by a detection bias, other studies underline the potential role of low levels of dihydrotestosterone in the genesis of high-grade tumours. In May 2008, a re-analysis of the PCPT results showed a significant decrease of 30% in the overall risk of prostate cancer in the finasteride group vs the placebo group, but it also found a statistically non-significant and less important increase of the prevalence of high-grade cancers in the finasteride group. However, the 5AR isoenzyme type 1 is present at higher rates than type 2 in high-grade cancers. Thus, finasteride is probably not the ideal drug to prevent high-grade cancers.