In 2003, the results of a seven-year study called the Prostate Cancer Prevention Trial were published, causing doctors to rarely prescribe the drug finasteride as a preventive measure. In the study of 18,882 healthy men over the age of 55, a percentage received finasteride, while others took a placebo. The drug, which is designed to reduce levels of the male hormone dihydrotestosterone and shrink the prostate, decreased the prevalence of prostate cancer by approximately 25 percent. However, it also seemed to suggest that those who were on the drug were 25 percent more likely to have a more aggressive form of the disease.

Now the mystery may have been solved: Researchers from Stanford University School of Medicine believe that finasteride doesn't induce more aggressive forms of the cancer, but makes them easier to diagnose. How did they arrive at this conclusion? Several researchers, including Dr. Joseph Presti Jr., noticed that the initial analysis of the study had not been able to detect a subtlety in the data; specifically that the increase in the aggressive “high-grade” cancers wasn't consistent across all groups. Furthermore, it occurred disproportionately in those men who had developed warning signs of the disease.

In men who had no warning signs, using finasteride did not make a difference in the rate of high-grade cancers diagnosed upon an exit biopsy. But the results were significantly different for men who were biopsied after having either an abnormal digital rectal exam or elevated levels of prostate-specific antigen (PSA), which is known to be unusually high in prostate cancer patients. Of those men, the ones on finasteride had an 11.5 percent rate of high-grade cancer, compared with 7.7 percent in the placebo group. That inconsistency suggested something wrong with the initial study analysis, not the drug.

The original study authors also had found evidence that PSA screening works better in men taking finasteride, but did not know the reason why. To test their hypothesis that it was due to finasteride's propensity to shrink the prostate, Dr. Presti and his colleagues analyzed a database of 1,304 men who were referred to the medical center after an abnormal digital rectal exam or high PSA test results. They discovered that the smaller the prostate, the more likely a biopsy would result in the diagnosis of a high-grade cancer -- and the more likely a high PSA level would predict the disease. “We're showing that this is all related to size,” says Presti. And says, Catherine Tangen, DrPH, who was one of the original researchers of the Prostate Cancer Prevention Trial and a member at Seattle's Fred Hutchinson Cancer Research Center, warns that “that without removing and analyzing the prostates of the men in Presti's study, the true prevalence of undetected prostate cancer remains unknown, leaving the actual sensitivity of the prostate-specific antigen test open to question.” But, she says, “Their observations are consistent with everything we found,” and suggest that men “should be given the opportunity to take finasteride if they and their doctors deem it necessary.”

News Release: Stanford study bolsters case for preventive prostate cancer treatment  http://www.businesswire.com/portal/site/google/?ndmViewId=news_view&newsId=20090707005010&newsLang=en  July 7, 2009