Andrew Vickers, Research methodologist and study author
The drug finasteride, used to treat benign enlargement of the prostate, has been shown in a large, randomized study to prevent prostate cancer, reducing the risk of the disease by close to 25 percent. However, the drug is not widely used as a preventive, which experts attribute to the modest benefit it offers to the average man. In a recent analysis of the data from the original study, investigators from Memorial Sloan Kettering Cancer Center have found that finasteride is best given only to men at higher than average risk of getting prostate cancer.
Prostate Prevention Trial
In June 2003, results from a large study funded by the National Cancer Institute, known as the Prostate Cancer Prevention Trial (PCPT), found that finasteride reduced the incidence of prostate cancer by about 25 percent. The study’s authors noted that regular use of the drug as a preventive could mean that as many as 50,000 of the approximately 192,000 American men diagnosed each year with prostate cancer would not develop the disease. This good news was tempered, however, by the associated finding that men in the trial who did develop prostate cancer while taking finasteride experienced a slightly higher incidence of high-grade tumors (37 percent versus 22 percent of men taking a placebo). These tumors grow faster and are more difficult to treat successfully.
Subsequent research, in which pathologists examined prostates removed during surgery, suggested that this increase in the number of high-grade tumors occurred because finasteride shrank the size of the study participants’ prostates, thereby making it easier to find high-grade tumors during needle biopsy. In effect, finasteride was not causing more high-grade tumors but was revealing more existing tumors in the smaller prostate glands of men taking the drug as compared with the larger prostates of men not taking the drug.
In general, a man has a less than 3 percent chance of dying from prostate cancer. Furthermore, most men who are diagnosed with prostate cancer will die with rather than from their cancers. Coupling those odds with the study’s initial findings regarding high-risk disease and the potential side effects of taking the drug, which include reduction in libido, relatively few men opted to use finasteride to prevent prostate cancer.
Re-Analysis of the PCPT Data
Investigators from Memorial Sloan Kettering analyzed 9,058 men from the original Prostate Cancer Prevention Trial, seeking to determine whether prostate-specific antigen (PSA) levels could be used to identify a high-risk subgroup of men for whom the benefits of finasteride treatment outweigh the potential harms.
Of the approximately 9,000 men analyzed, 1,957 were diagnosed with prostate cancer during the seven-year study. In the group of men receiving finasteride, about 18 percent were diagnosed with prostate cancer, compared with about 25 percent of the men in the control group receiving a placebo. Factors such as age, race, family history of prostate cancer, and PSA levels were similar for both groups.
Study Results
The results of this analysis [PubMed Abstract], published in the March 2010 issue of the Journal of Clinical Oncology, revealed that finasteride had the largest effect on men at higher risk, defined as men with above-average PSA levels. As a result, the study’s authors found that the drug is best prescribed only to this subset of the population. For example, using finasteride only for men with PSA levels greater than 1.3 ng/ml would reduce the number of men being treated with finasteride by 62 percent when compared with treating all men with the drug. This would be accompanied by only a small 0.3 percent increase in cancer rates. When they looked at using finasteride only for men with a PSA of greater than or equal to 2 ng/ml, it reduced the treatment rate by 83 percent, with a 1.1 percent increase in prostate cancers.
Further analysis was performed to determine whether taking age, family history, or race into account could improve the predictive ability for which men should be considered high risk, but the additional information proved only very slightly better than PSA alone.
Consequently, the study’s authors concluded that using finasteride to treat men with PSA levels greater than 1.3 or 2 ng/ml is the optimal strategy for reducing the risk of prostate cancer. “It is common in medicine to assess patient risk and then treat only those patients at high risk,” says lead author and research methodologist Andrew Vickers. “In the case of disease prevention, however, we seem to have abandoned risk stratification in favor of an all-inclusive policy of treating everyone,” he notes. “We have shown using a simple statistical analysis that the best approach to preventing prostate cancer is to treat only men with above-average PSA levels — either 1.3 ng/ml or 2.0 ng/ml, depending on how men feel about the side effects of finasteride.”
