Finasteride (Proscar) Associated with Boost in Detection of High-Grade Prostate Cancer

DENVER, Sept. 13 -- The increase in high-grade prostate cancer seen among men taking finasteride (Proscar) is probably caused by increased detection, two groups of researchers said.
Although a seven-year study reported in 2003 showed that finasteride reduced the occurrence of prostate cancer by 24.8%, compared with placebo, it also showed that finasteride patients had a significant increase in the rate of lesions with Gleason scores of 7 or higher.
Now the researchers have reported online in the Journal of the National Cancer Institute that the finding of high-grade lesions, which alarmed many physicians and patients, was mainly a result of better detection among finasteride patients.
Both studies used data from the original study, expanded to include several hundred participants whose outcome status wasn't known at the time of the original report.
According to M. Scott Lucia, M.D., of the University of Colorado Health Sciences Center and colleagues, degenerative hormonal changes in high-grade biopsies were equivalent between the groups, but prostate volumes were significantly smaller (at P<0.001) in the finasteride group - 25.1 cc versus 34.4.
The smaller volume would make detection of high-grade tumor cells more likely on biopsy. Dr. Lucia and colleagues said.
Also, they noted that among finasteride patients who had a prostatectomy during the study, the rate of high-grade disease - which was significantly elevated at biopsy compared to those taking placebo - was equivalent to placebo when tumors were graded after surgery.
Although it's not possible to rule out the alarming possibility that finasteride induces high-grade tumors, Dr. Lucia and colleagues said, their results "suggest that high-grade cancer was detected earlier and was less extensive in the finasteride group than in the placebo group."
A similar conclusion was reached by Peter Gann, M.D., Sc.D., of the University of Illinois at Chicago and colleagues with Merck, which makes the drug.
Dr. Gann and colleagues performed an "observational re-analysis" of the data from the original study, asking whether the likelihood of detection of high-grade disease at biopsy varied depending on the size of the gland.
In fact, they said, a logistic model based on the placebo group showed that the likelihood of finding high-grade cancer decreased as volume increased.
Specifically, for each increase of 10 cc, the chance of detecting high-grade cancer by biopsy fell by 19%. The odds ratio was 0.81, with a 95% confidence interval from 0.74 to 0.90.
On the basis of the model, Dr. Gann and colleagues said 239 high-grade lesions would be expected among the finasteride patients - not significantly different from the 243 that were observed.
When prostate volume was used as a covariate, the odds ratio for high-grade cancer in the finasteride group, compared to placebo, fell from a significant 1.27 to a non-significant 1.03, they found.
Both groups of researchers cautioned that their conclusions are based on post hoc analyses of the data, and should be evaluated carefully. Dr. Gann and colleagues said their findings "must be interpreted cautiously and (do) not allow us to recommend definitive changes in clinical practice."
Nevertheless, the studies taken together seem to show that the increased rate of high-grade cancer "is not likely to be clinically relevant," commented Gerald Andriole, M.D., of Washington University School of Medicine in St. Louis, and colleagues.
Writing in an accompanying editorial, they noted that despite the "impressive" drop in cancer occurrence among finasteride patients, the drug "has not been embraced in clinical practice."
That was largely the result of disquiet about the possibility that the drug was somehow inducing high-grade cancer, they said - a worry that still can't be completely dispelled despite the "substantial reassurance" provided by the two new studies.
Dr. Andriole and colleagues suggested that the results of a study of a sister drug to finasteride - dutasteride - are due in the next few years and should provide better information on the safety of this class of medications.
All authors of the Chicago study except Dr. Gann were paid employees of Merck, which makes finasteride. The Denver study was supported by the National Cancer Institute and Merck. Dr. Lucia has been a scientific consultant for GlaxoSmithKline, and coauthors Michael Kattan, Ph.D., and Jonathan Epstein, M.D., have been consultants for Merck. Primary source: Journal of the National Cancer InstituteSource reference: Cohen YC et al. "Detection Bias Due to the Effect of Finasteride on Prostate Volume: A Modeling Approach for Analysis of the Prostate Cancer Prevention Trial." J Natl Cancer Inst 2007; 99: 1366-74. Additional source: Journal of the National Cancer Institute Source reference: Lucia MS et al. "Finasteride and High-Grade Prostate Cancer in the Prostate Cancer Prevention Trial." J Natl Cancer Inst 2007; 99: 1375-83. Additional source: Journal of the National Cancer Institute
Source reference: Andriole GL et al. "High-Grade Prostate Cancer in the Prostate Cancer Prevention Trial: Fact or Artifact." J Natl Cancer Inst 2007; 99: 1355-56.