In the quest to find a way to prevent prostate cancer, finasteride (Proscar) was once a rising star -- until evidence showed a potential link between it and high-grade prostate cancer. Now research suggests that this and other concerns are unfounded. But not everyone is convinced. Two Hopkins specialists weigh in on the debate.
The debate began in 2003 with the publication of the Prostate Cancer Prevention Trial (PCPT). In this randomized clinical trial, more than 18,000 men age 55 and older took either 5 mg of Proscar or a placebo every day for seven years. The aim of the study was to determine whether Proscar -- which belongs to the class of medications known as 5-alpha-reductase inhibitors and is commonly prescribed to treat benign prostatic hyperplasia (BPH) -- might also reduce a man's chances of developing prostate cancer.
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Results of the PCPT did, in fact, show a 25% reduction in prostate cancer among men taking the drug. But there was a serious catch: Men who developed prostate cancer had an increased likelihood of having higher-grade, more aggressive cancers (Gleason scores of 7 to 10). This finding dampened enthusiasm for using Proscar as a preventive agent against prostate cancer.
New Studies, Different Interpretations -- Two new analyses of the PCPT data -- one published in Urology and the other in Cancer Prevention Research -- were released in May 2008. Each confirms the earlier trial's conclusion that Proscar reduces the risk of prostate cancer. A third analysis published in Cancer Prevention Research re-examined the problem of high-grade tumors. Instead of basing the grade of the prostate cancer on tissue samples from biopsies, the researchers looked at prostate tissue removed from men who underwent radical prostatectomy to treat their prostate cancers. When this tissue was graded, the researchers found that finasteride actually reduced the development of these aggressive prostate cancers by 27% compared with placebo.
Based on these findings, some prostate cancer specialists now support the idea of using Proscar for prostate cancer prevention. But two prominent prostate cancer experts from the Johns Hopkins University School of Medicine -- Patrick C. Walsh, M.D., and H. Ballentine Carter, M.D. -- disagree with these new interpretations.
Two Hopkins Experts Weigh In -- Drs. Walsh and Carter point out that the reduction in prostate cancer cases among men taking Proscar may simply reflect the fact that fewer of these men underwent prostate biopsies. In the PCPT, the men had a for-cause biopsy when there was an abnormality on their digital rectal examination (DRE) or when their PSA level rose higher than 4 ng/mL. Men with a normal DRE and PSA level were offered a biopsy at the end of the seven-year study, but many refused.
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The reason: Proscar not only shrinks the prostate but also reduces PSA levels by about half. These artificially low PSA levels in Proscar users can lull some men and their doctors into a false sense of security and prevent needed biopsies.
The finding of a 25% reduction in prostate cancer cases was determined from both the for-cause and end-of-study biopsies. In the real world, however, men only undergo biopsies for cause. When the end-of-study biopsies are removed from the analysis, Proscar users had only a 10% reduction in prostate cancer -- a difference that is much smaller than 25% and is not statistically significant.
The Issue of High-Grade Disease -- So what do the Hopkins experts think about the high-grade tumor problem? First, if the original finding is correct -- that Proscar use increases the risk of high-grade prostate cancer by 68% -- then the drug could do more harm than good in terms of prostate cancer prevention, because at best, it only reduces the overall risk of getting prostate cancer by 25% and at worst, by a mere 10%.
Second, it can't be said with confidence that Proscar reduces the risk of high-grade prostate cancer, because the results of the reanalysis were based on a small number of cases; only 500 men in the study had a prostatectomy.
Our Advice -- Don't take any 5-alpha-reductase inhibitor in hopes of preventing prostate cancer. In addition to Proscar, drugs in this class include Propecia (a form of finasteride used to prevent baldness) and the BPH drug dutasteride (Avodart). If you do use these drugs for BPH or hair loss, there's no need to stop, but it's necessary to get a biopsy right away if your PSA level increases.
Moreover, because 5-alpha-reductase inhibitors lower PSA levels by about 50%, if you use any of these medications you must multiply your PSA by two for the first two years of use, by 2.3 for the second to seventh year, and by 2.5 if you've used the drug for seven or more years. This is extremely important, because if your PSA is rising, your risk of having cancer is three times as high as that of men who don't have a rising PSA, and you're six times as likely to be diagnosed with high-grade disease.
