But Not All Men Benefit
Results from the Prostate Cancer Prevention Trial (PCPT) revealed that men who received finasteride, a drug that affects male hormone levels, reduced their chances of developing prostate cancer by nearly 25% compared to men who received a placebo for seven years.
These findings resulted in the early closing of the study in June 2003, which was coordinated by a network of researchers called the Southwest Oncology Group (SWOG) and funded by the National Cancer Institute (NCI). The 10-year trial, involving nearly 19,000 men nationwide, was originally scheduled to end in May 2004.
"Finasteride is the first drug found to reduce the risk of prostate cancer," said Ian Thompson, MD, professor and chief of the division of urology at the University of Texas Health Sciences Center, who led the study. Age, prostate specific antigen (PSA) level at enrollment, family history of prostate cancer, and race, or ethnicity did not affect the drug's ability to prevent the disease.
According to Dr. Thompson, there is a cautionary note. Men in the study who developed prostate cancer while taking finasteride were more likely to have high-grade cancers, which, when found in the general population, may spread quickly even if the tumors are small. But, more than 97% of men who did develop prostate cancer during this study had early-stage cancers, which are most often curable.
The reason men on finasteride had more high-grade tumors is currently unknown, but the researchers are studying several possibilities. The drug affects the appearance of prostate cancer cells, and this may lead to a false estimate of tumor grade, which is determined visually by a pathologist. Another possible explanation being examined is whether finasteride truly causes more aggressive tumors to develop.
Prostate cancer is the most common cancer in men, after skin cancer, and will affect nearly 221,000 men in the US in 2003; about 29,000 will die of the disease. The disease, as well as its treatment--which sometimes leads to impotence, urinary incontinence, and other problems-causes a significant health burden for men.
"Millions of men have the potential to benefit from finasteride's ability to reduce prostate cancer risk," said Leslie Ford, MD, associate director for clinical research in NCI's Division of Cancer Prevention, who oversaw PCPT for the Institute. "As with any medical procedure or intervention, a decision to take finasteride is an individual one in which the benefits and risks must be considered."
Finasteride is used in its 5 mg (Proscar®) dose for treating benign prostatic hypertrophy (BPH), a noncancerous enlargement of the prostate that can cause problems with urine flow. The drug is also used at a 1 mg dose (Propecia®) to treat male pattern baldness. In PCPT, healthy men ages 55 and older were randomly assigned to take either 5 mg finasteride or placebo daily for seven years. Neither the participants nor their doctors knew which men were assigned to take which pills.
Men chosen for PCPT showed no evidence of prostate cancer at the start of the trial. To enter, men needed to have a normal digital rectal exam (DRE) and a PSA level of 3.0 ng/ml or less. These tests were repeated annually. The participants also agreed to have a prostate biopsy after they had participated for seven years. At the time the trial ended, about 9,000 men had undergone biopsies.
PCPT researchers will continue to monitor the men who participated in the trial at the more than 200 sites around the country. "What these men have already given us is priceless," said Dr. Thompson. "But, we will continue to learn much more. The participants provided us with blood and biopsy samples, and this repository of biological materials will prove invaluable in learning more about the molecular changes that happen as prostate cancer develops."
On March 3, 2003, the Data and Safety Monitoring Committee, an independent body that periodically examined the study, advised that the trial be closed early. The recommendation came because data collected were sound, and the conclusions were extremely unlikely to change with the addition of more data.
By the close of the study, prostate cancer had been found in about 18% of the men who received finasteride; about 24% of men who received the placebo also had been diagnosed with prostate cancer. Many of the men with cancer had normal DREs and PSA levels; malignancies were found only because the trial required an end-of-study biopsy.
Despite the fact that men taking finasteride had fewer prostate cancers overall, they had a greater proportion of high-grade prostate cancers. Overall, just over 6% of men on finasteride developed high-grade tumor; 5% of the men who received the placebo developed high-grade cancers. PSA level did not correlate with the development of aggressive tumors--some of the men in both groups of the trial had high-grade disease despite having very low PSA levels.
The researchers regularly monitored participants for side effects. Compared to men on placebo, more men taking finasteride experienced sexual side effects at some point during the study. On the other hand, urinary symptoms were reported by more men taking placebo.
"PCPT and its findings mark a milestone for the field of cancer prevention, and we will continue to learn more in the years to come," Ford said.
The Influence of Finasteride on the Development of Prostate Cancer," appeared in the July 17, 2003 issue of the New England Journal of Medicine, along with an editorial, "The Prevention of Prostate Cancer-the Dilemma Continues." Please visit the Web site (http://content.nejm.org/) to view both of these articles. 
