Finasteride Not Linked to High-Grade Prostate Cancer

Roxanne Nelson

June 20, 2008

June 20, 2008 — A new analysis from the national Prostate Cancer Prevention Trial (PCPT) shows that finasteride does not increase the risk for high-grade prostate cancer, as earlier findings appeared to indicate. These latest data, published online May 18 in Cancer Prevention Research, demonstrate that chemopreventive treatment with finasteride for 7 years decreases the incidence of prostate cancer by an estimated 30%, without increasing the incidence of high-grade tumors.

"We do believe that our results indicate that finasteride use should be seriously considered and men at high risk should discuss it with their doctors," lead author Mary Redman, PhD, a biostatistician at the Fred Hutchinson Cancer Research Center, in Seattle, Washington, told Medscape Oncology.

The PCPT randomized 18,882 men older than 55 years to receive either finasteride or a placebo for 7 years; the initial results were published in 2003 in the New England Journal of Medicine (2003;349:213-222.). Despite a relative reduction of nearly 25% in the 7-year prevalence of prostate cancer attributable to finasteride, it has not been accepted clinically for chemoprevention. The primary reason for the reluctance to use finasteride in this setting is that the initial results showed a greater proportion and number of histologically high-grade carcinomas, defined as a Gleason score of 7 to 10, among the men who had received finasteride.

Even though high-grade tumors represented a relatively small proportion of all tumors detected in the finasteride group, note the researchers, the potentially elevated risk for aggressive disease and an unfavorable editorial that accompanied the initial publication led to a general lack of acceptance of finasteride for cancer prevention.

"Other noted side events in the primary publication were reduced volume of ejaculate, erectile dysfunction, loss of libido, and gynecomastia," said Dr. Redman. "The noted benefits were decreased urinary urgency, urinary frequency, prostatitis, urinary tract infection, and urinary retention."

New Analyses Show No Increase in Aggressive Cancer

Subsequent analyses, however, appear to have quelled the fear that finasteride increased the incidence of high-grade prostate cancer. One study, published in 2007 in the Journal of the National Cancer Institute (2007;99:1375-1383), reported that the higher number of aggressive cancers was most likely due to an increased rate of cancer detection. A reanalysis released at the American Urological Association 2008 Annual Meeting also found that finasteride did not raise the incidence of high-grade prostate tumors but, in fact, lowered the risk for most prostate cancers.

In the current study, Dr. Redman and colleagues conducted 3 analyses of the PCPT data. In the first analysis, they used data that included end points 3 months longer than in the original report, and analyzed the effect of finasteride on overall and high-grade prostate cancer in all study participants to account for possible selection bias. The initial data showed prostate cancer rates of 22.9% in the placebo group (4.8% high grade) and 16.6% in the finasteride group (5.8% high grade). The new analysis suggests that if all the study participants had had a biopsy end point, the actual cancer rate would have been 21.1% in the placebo group and 14.7% in the finasteride group. The true rates of high-grade cancer, according to this analysis, were 4.2% and 4.8%, respectively.

They also estimated the true prevalence of high-grade prostate cancer among the 500 men with biopsy-detected cancer who underwent a radical prostatectomy. Their estimates showed a rate of high-grade cancer of 8.2% in the placebo group and 6.0% in the finasteride group, indicating that finasteride reduced the risk for aggressive cancers by 27%. The estimated risk reduction with finasteride for a Gleason score of 6or less was 34%; for a Gleason score of 7 or more, it was 27%.

In the third part of their analyses, the researchers found that small differences in biopsy sensitivity between the 2 groups could result in the apparent increase in high-grade disease that was initially reported in patients taking finasteride.

"The take-home message from this study is that men at high risk for prostate cancer should seriously consider taking finasteride," said Dr. Redman. "The potential for undesirable side effects is low and, if they are experienced and determined to be intolerable, the effects of finasteride are not long lasting and will generally go away if treatment is stopped."

Promise of Chemoprevention

In an accompanying editorial, Christopher J. Logothetis, MD, from the University of Texas MD Anderson Cancer Center, in Houston, and Paul F. Schellhammer, MD, from Eastern Virginia Medical School, in Norfolk, agree that finasteride is a safe and effective prevention option that should be offered to men at risk for prostate cancer.

They also note the importance of using the PCPT as a basis for developing more effective preventive agents that can be used alone or in combination.

"Based on the advances reported for finasteride in this issue of the journal, we conclude that the promise of prostate cancer prevention is a reality and that the findings of the PCPT provide the impetus and foundation for the further studies suggested here," write the editorialists.

The study was funded by the National Cancer Institute. Dr. Redman has disclosed no relevant financial relationships. Several study author report consulting for GlaxoSmithKline, Seno Medical, or Veridex.

Cancer Prev Res. Published online before print May 18, 2008.

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