Link between high prostate specific antigen count and prostate cancer questioned

A comprehensive re-evaluation of the largest prostate cancer prevention study ever completed produced new findings suggesting that men and their doctors should consider a more aggressive approach that includes finasteride to prevent the development of prostate cancer.

A companion study sheds light on the importance of prostate specific antigen (PSA) scores in treatment decision-making. Researchers found that even those men who have a low PSA screening value can have cancer that is difficult to cure.

The two studies will be published in the June 2008 issue of Cancer Prevention Research.

The original study, the Prostate Cancer Prevention Trial (PCPT), randomised 18,822 men to receive either a placebo or an agent known as finasteride, currently approved to control prostate growth, for seven years. Results showed that while finasteride reduced prostate cancer risk by 25 percent, it appeared to increase development of fast-growing prostate cancer in some men. Because of this finding and concerns that tumours detected had low PSA values and might be of little risk to patients, since the study's original publication in 2003, few doctors have recommended finasteride for prostate cancer prevention.

From a new analysis of PCPT data using advanced modelling techniques and a complete assessment of prostate tissue biopsies, they concluded that these concerns are now resolved: finasteride actually reduced the risk of developing prostate cancer more than researchers had originally thought, did not increase development of fast-growing cancers, and the majority of tumours prevented were those that could spread and cause death.

These new findings suggest that men should take an "individualised" approach to prostate cancer prevention, says Ian M. Thompson, M.D., Chair of the Department of Urology at the University of Texas Health Sciences Center at San Antonio, who is senior author on both studies, and was also lead author for the Southwest Oncology Group (SWOG) on the original PCPT results paper, which was published in July 2003.

"Because we now know that men with even low PSAs can develop prostate tumours, if a man is worried about his risk, regardless of PSA score, he can take an agent that is now proven to be effective in lowering that risk," Thompson said.
Researchers looked at whether finasteride actually increased cancer progression in some men, and by studying biopsies and prostate gland tissue that had been removed, concluded that it did not. "Finasteride actually shrank the prostate gland, so it appeared in initial studies that more cancer was being found in biopsies of men who took the drug," said Mary Redman, Ph.D., a biostatistician at the Fred Hutchinson Cancer Research Centre.

"What that means is that the cancer took up more prostate tissue in men who were treated, and that is why it was easier to find in a biopsy. Cancer was probably missed more often in biopsies of men on a placebo drug because the prostate gland itself was larger," Redman said.

Redman found that in addition to a 25 to 30 percent reduction in prostate cancer development overall in men taking finasteride, the drug decreased the rate of diagnosis of fast-growing cancer by 27 percent. "There were more lower grade tumours in treated men than in men who used a placebo," she said. "We think men should not be concerned about using finasteride."

The second study examined whether men in the trial who had a low PSA level were actually at risk of developing significant disease. With about 75 percent of the tumours classified as those which could take a man's life, researchers concluded that there is no clear-cut PSA threshold that can be considered normal.

All patients in PCPT were to have a biopsy of their prostate