Men who took finasteride to prevent prostate cancer as part of a randomized clinical trial that ended in 2003 had the same long-term mortality as did those who took placebo, according to a report published online Aug. 14 in the New England Journal of Medicine.
The 15-year survival was approximately 78% in both groups, said Dr. Ian M. Thompson Jr. of the Cancer Research and Therapy Center, University of Texas Health Science Center at San Antonio, and his associates.
"The use of finasteride over a period of 7 years in a general population of men with a median age at study entry of 63.2 years reduced the risk of prostate cancer but did not significantly affect mortality. This reduction in risk was due entirely to a relative reduction of 43% in the risk of low-grade cancer among men receiving finasteride, as compared with placebo," the researchers wrote
Dr. Ian M. Thompson
The original randomized controlled study, the Prostate Cancer Prevention Trial, enrolled 18,882 men in 1994-1997 and followed them regularly for the development of the disease. Approximately half were randomly assigned to take the 5-alpha-reductase inhibitor finasteride and half to take placebo for 7 years. Data collection and prostate-cancer assessments continued for up to 10 years for most of the study participants.
In the initial analysis of the data in 2004, finasteride had reduced the relative risk of prostate cancer by 24.8%. However, it also appeared to raise the relative risk of high-grade tumors by 26.9%.
In 2011, the Food & Drug Administration mandated labeling changes for all 5-alpha-reductase inhibitors, stating that the drugs are not approved for use as preventives and they may raise the risk of high-grade prostate cancers.
Finasteride likely reduced prostate-specific antigen (PSA) levels in men who had benign enlargement of the prostate, causing the prostate to shrink. This is probably the reason why the drug improved the sensitivity of PSA testing, prostate biopsy, and digital rectal examination for the detection of high-grade disease, Dr. Thompson and his colleagues said.
"Despite multiple analyses suggesting that [such] detection bias accounted, at least in part, for the observed increase in the rate of high-grade tumors in the finasteride group, concern regarding this potential risk has all but eliminated the use of finasteride for prostate-cancer prevention," they noted.
Dr. Thompson and his associates reasoned that if the increase in high-grade prostate cancers wasn’t just an artifact of detection but in fact reflected finasteride-induced tumors "some increase in mortality among men receiving finasteride should become obvious during long-term follow-up." They therefore performed a post hoc analysis of long-term survival in the study population "to seek any evidence of an increased risk of death among men in the finasteride group, since such an increase would be a potentially accurate indicator of an increase in the risk of high-grade (and hence more lethal) cancer."
Long-term follow-up was hampered by the fact that many of the study centers closed, and direct contact with many participants was lost. The Social Security Death Index was used to assess the subjects’ survival status through 2011. The cause of death was not available for most of the men, so prostate-cancer-specific mortality could not be assessed. In addition, "since the total number of high-grade cancers was small and there were only a total of 177 deaths in this subgroup, there was not enough information to formally test noninferiority," the researchers said.
Nevertheless, they found that prostate cancer developed in 10.5% of the finasteride group and 14.9% of the placebo group, confirming that finasteride significantly reduced the risk of the disease.
A total of 3.5% of the tumors in the finasteride group and 3% in the placebo group were high-grade cancers.
Fifteen-year survival was 78% with finasteride and 78.2% with placebo, a nonsignificant difference. The median age at which prostate cancer was diagnosed also was the same in both groups: 70 years, the researchers said (N. Engl. J. Med. 2013 Aug. 14;369:603-10).
"Although the prevention of these tumors did not appear to reduce overall mortality, increased diagnosis of low-grade prostate cancer is a problematic byproduct of PSA testing, in that treatment adds little, if any, benefit and in that all forms of therapy cause considerable burden to the patient and to society," they concluded.
This study was funded by the National Cancer Institute. Merck provided the finasteride and placebo for the PCPT but wasn\'t involved in the design, oversight, data analysis, or decision to publish that trial. Dr. Thompson reported ties to Ferring and is listed as an inventor on 2 patent applications concerning prostate cancer and erectile dysfunction. One of his associates reported being a consultant for Amgen and Eli Lilly.