Do Not Use Finasteride (PROSCAR, PROPECIA) For Preventing Prostate Cancer

The results of a major study examining the effect of finasteride (PROPECIA, PROSCAR) in reducing the risk of prostate cancer was released early, June 24, 2003, on the web site of the New England Journal of Medicine (www.nejm.com). The results of the study were mixed, with the increased risk of high-grade cancer caused by the drug outweighing the decreased risk of cancers that may be of little clinical significance.

Finasteride is sold by Merck & Company, Inc. of West Point, PA as Proscar for the treatment of symptomatic benign prostatic hyperplasia (enlarged prostate) and as the life-style drug Propecia for male pattern baldness.

The study is known as the Prostate Cancer Prevention Trial (PCPT) and was sponsored by the U.S. Public Health Service and the National Cancer Institute, one of the National Institutes of Health.

The rationale for trying finasteride to reduce the risk of prostate cancer is the mechanics by which the drug works. Finasteride inhibits the enzyme 5 alpha-reductase that is responsible for converting the male hormone testosterone to the more potent dihydrotestosterone. The theory is that lowering the level of the more potent hormone in the prostate would reduce the risk of prostate cancer.

In the PCPT trial, 18,882 men 55 years of age or older with normal physical examinations and prostate-specific antigen (PSA) levels of 3.0 nanograms per milliliter or lower were randomly assigned to receive finasteride, five milligrams per day, or a placebo for seven years. This type of study design is the scientific “gold standard” for showing a cause and effect relationship between a treatment and an outcome.

At seven years there were 9,060 men included in the final analysis. In 4,368 men given finasteride, 803 cases (18.4%) of prostate cancer were diagnosed. In the group of 4,692 men receiving the placebo, 1,147 men (24.4%) developed prostate cancer. (As discussed below, most of these are low-grade cancers of little clinical significance.)

The results were reported in the study and in the news media as a 24.8 percent relative reduction in prostate cancer risk after seven years. Regular readers of Worst Pills, Best Pills News know that the reporting of a relative risk reduction can be misleading unless it is reported along with the absolute risk reduction between the finasteride and placebo groups. In the PCPT study, the difference in the risk of developing prostate cancer between the finasteride and placebo groups was six percent (24.4% - 18.4% = 6.0%).

By knowing the absolute risk reduction between the finasteride and placebo groups, the number of men who need to be treated with finasteride to prevent one case of prostate cancer can be calculated: 16 men must be treated for seven years to prevent the detection of one case of prostate cancer.

In other words, 16 men must be treated for seven years to prevent one case of prostate cancer; we can not predict which one of the 16 men will benefit; and the other 15 men face the risks of using the drug, which may be substantial.

At the end of the study, 5.1 percent of men receiving the placebo and 6.4 percent of those taking finasteride who had biopsies of their prostate glands had developed high-grade cancers. This is an increase of 1.3 percent. High-grade prostate cancers are known to behave aggressively.

Because the difference in the percentage of high grade cancers between the finasteride and placebo groups is known, a number analogous to the number needed to treat, the number needed to harm can also be calculated. This number is 77. In other words, at the end of seven years of taking finasteride, for every 77 taking the drug one additional man will develop a high-grade cancer.

The table below summarizes the other adverse effects and the effects on the urinary systems of the men who participated in the PCPT trial.

The editorial appearing in the same issue of the New England Journal of Medicine as the PCPT trial, written by a urologist from the Memorial Sloan-Kettering Cancer Center, addressed the important question “What should we advise the public and our patients?” about using finasteride to prevent prostate cancer. His conclusion was “On balance, finasteride does not seem to be an attractive agent for the chemoprevention of prostate cancer.” We agree.

The editorial went on to say that although finasteride was shown to reduce the incidence of cancers, and that because the study required that prostate biopsy be recommended for all men, this may have led to the overdetection of cancers of little clinical significance:

We do not know the malignant potential of such cancers and have no evidence that any benefits would be worth the risk associated with treatment. Furthermore, the 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. Finally, the effects of finasteride on sexual function lessen the attractiveness of the drug as a preventive agent [see the table accompanying this article].

The Health Research Group has consistently held the position that before any drug can be recommended to prevent cancer, or any other disease, in otherwise healthy people, it must be almost entirely free of adverse effects.

The editorial also raised the question of what to tell men who are taking finasteride long-term to control the symptoms of enlarged prostate. The editorial suggests that these men be monitored carefully for the development of cancer by periodic physical examinations and following PSA blood levels. Unfortunately, the definition of periodic was not given and we are not aware of the optimal time for monitoring the possible development of aggressive prostate cancer in men taking finasteride long term for the symptoms of enlarged prostate.

What You Can Do

You should not be using finasteride at this time to reduce the risk of developing prostate cancer because of the increased risk of developing high-grade aggressive tumors.

If you are now using finasteride long-term to manage the symptoms of enlarged prostate you should discuss the result of the PCPT trial with your physician.