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Clinical Trial Results

Summaries of Newsworthy Clinical Trial Results
  • Posted: 08/28/2013

Finasteride Reduces the Risk of Low-Grade Prostate Cancer in Men 55 and Older

Summary

Long-term follow-up results from a phase III trial called the Prostate Cancer Prevention Trial (PCPT) continue to show that regular use of finasteride (Proscar®) for up to 7 years decreased the risk of low-grade prostate cancer in men age 55 and older compared with that in men who received a placebo. Although high-grade cancers were more common in the finasteride group, the finasteride and placebo groups had similar 15-year overall survival rates.

Source

New England Journal of Medicine (NEJM), August 14, 2013 (See the study abstract.)

Background

Launched in January 1994, the PCPT was a large randomized clinical trial designed to test whether the drug finasteride could help prevent prostate cancer in men age 55 and older. Finasteride blocks the activity of 5-alpha reductase, an enzyme that helps control the activity of the hormone testosterone. This hormone influences the size of the prostate and can fuel the growth of prostate tumors.

Finasteride was approved by the Food and Drug Administration in 1992 for the treatment of benign prostatic hyperplasia and is also approved to treat male pattern baldness. It has not been approved for preventing prostate cancer.

The PCPT was stopped in February 2003, 15 months earlier than planned, when a scheduled data analysis showed a 25 percent reduction in prostate cancer risk among participants taking finasteride compared with those taking a placebo (and a 38 percent reduction in risk of low-grade prostate cancers). That original analysis also showed a small but statistically significant increase in the risk of high-grade prostate cancer—cancers with a Gleason score of 7 to 10, which are considered more likely to be aggressive and life threatening—in the men taking finasteride. The original analysis focused on the men who had undergone a biopsy or other diagnostic procedure during the trial (approximately half of the study population), whereas the updated analysis included the entire study population.

Subsequent analyses of the PCPT data suggested that the observed increase in high-grade prostate cancers in men taking finasteride was due, at least in part, to improved detection. For example, finasteride shrinks the volume of the prostate, potentially making high-grade cancers easier to detect on biopsy. However, concerns that finasteride might cause a true increase in the risk of high-grade prostate cancer—and death—have remained, so the PCPT investigators analyzed long-term follow-up data for trial participants to look for mortality differences between finasteride-treated men and placebo-treated men.

The Study

Nearly 19,000 men age 55 and older who were in good health and showed no evidence of prostate cancer were enrolled in the PCPT. The men were randomly assigned to take 5 mg of finasteride or a placebo daily for 7 years. The study’s primary endpoint was prostate cancer incidence.

Participants in the trial had their health status monitored at regular intervals, including two tests conducted annually to look for signs of prostate cancer: a digital rectal exam and a prostate-specific antigen (PSA) test. At the end of the study, the researchers asked participants who had not been diagnosed with prostate cancer to have a prostate biopsy to check for prostate tumors.

The updated results published in NEJM included up to 18 years of follow up on all trial participants, including prostate cancer incidence data for an additional year beyond the period previously reported and mortality rates for men in the trial, which the researchers gathered using data from the Social Security Death Index (SSDI) from the time the trial was stopped through October 2011. The SSDI does not provide information about the cause of death.

This NCI-funded study was conducted by SWOG and led by Ian Thompson, MD, of the University of Texas Health Science Center at San Antonio.

Results

In the updated analysis, men taking finasteride had a 30 percent decrease in the relative risk of developing prostate cancer compared with men who took a placebo: 10.5 percent of men in the finasteride group were diagnosed with prostate cancer versus 14.9 percent of men in the placebo group. This reduction in risk was explained solely by the prevention of low-grade cancers—those with a Gleason score of 6 or less—which present little health risk but, nonetheless, are often treated with radical surgery or radiation. The risk of such cancers was 43 percent lower in the finasteride group than the placebo group.

The men who took finasteride were more likely to be diagnosed with high-grade cancer compared with the men who took a placebo: 3.5 percent of all men in the finasteride group versus 3.0 percent of all men in the placebo group, a relative increase of about 17 percent.

The survival rates at 15 years were very similar between the two groups: 78.0 percent in the finasteride group versus 78.2 percent in the placebo group. When the researchers looked specifically at men who had been diagnosed with prostate cancer, the survival rates for individuals diagnosed with prostate cancer were also very similar between the two groups.

Limitations

Howard Parnes, MD, of NCI’s Division of Cancer Prevention and a co-author of the study, noted that the increased risk of high-grade cancer in the finasteride group “was a secondary finding, which the trial was not specifically designed to address.”

Because information on the cause of death for the majority of participants who died was not available for the trial update, prostate cancer-specific mortality could not be determined. This is important, wrote Michael LeFevre, MD, MSPH, in an accompanying editorial, because “a small difference in [prostate cancer-specific] mortality can exist in the absence of a difference in all-cause mortality.”   

Comment

Nevertheless, the study shows that, “for men who choose regular prostate-cancer screening, the use of finasteride meaningfully reduces the risk” of being diagnosed with the disease and, as a result, of any side effects associated with prostate cancer treatment, Dr. LeFevre wrote.

“Whether the use of the drug has either a positive or a negative effect on prostate-cancer-specific mortality remains unknown,” continued Dr. LeFevre, “but either way the effect is probably very small and does not result in any difference in life expectancy.…For men who choose regular prostate-cancer screening, the use of finasteride meaningfully reduces the risk of prostate cancer and thus the morbidity associated with treatment of the disease,” he concluded.

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