The 5α-reductase inhibitor finasteride (Proscar), an agent commonly used to treat lower urinary tract problems and baldness in men, was found to be safe and effective in reducing the risk of prostate cancer.
Ian Thompson, Jr, MD
The 5α-reductase inhibitor finasteride (Proscar), an agent commonly used to treat lower urinary tract problems and baldness in men, was found to be safe and effective in reducing the risk of prostate cancer, according to the final analysis of the Prostate Cancer Prevention Trial (PCPT) published in the New England Journal of Medicine.1
“Finasteride is safe, inexpensive, and effective as a preventive strategy for prostate cancer,” principal investigator Ian Thompson, Jr, MD, chair of SWOG's Genitourinary Cancer committee, and president of CHRISTUS Santa Rosa Hospital Medical Center, said in a press release. “Doctors should share these results with men who get regular prostate-specific antigen (PSA) tests that screen for the presence of prostate cancer. The drug will have its greatest effect in this group of men.”
Funded by the National Cancer Institute, the initial SWOG Cancer Research Network PCPT trial first opened for enrollment in January 1993. In the trial, 18,882 men aged ≥55 years with a normal digital rectal exam and a PSA level ≤3.0 ng/ml were randomized to receive 5 mg of finasteride daily (n = 4368) or placebo (n = 4692) for 7 years.
Patients were excluded from the first analysis if they had a prior diagnosis of prostate cancer (n = 2), had failed to complete the study due to early termination (n = 2585), died (n = 1123), refused end-of-study biopsy (n = 3927), were lost to follow-up (n = 1256), had data that was still in review (n = 64), or had an end-of-study biopsy after randomization cut-off (n = 865).
Of the 9060 men who were included in the first analysis, prostate cancer was detected in 18.4% of men (n = 803) in the finasteride arm and 24.4% of men (n = 1147) in the placebo arm, resulting in a 24.8% reduction in the prevalence of prostate cancer over the 7-year span (HR, 0.75; 95% CI, 18.6%-30.6%; P <.001).
The percentage of men who experienced sexual adverse events was higher in the finasteride arm, whereas men in the placebo arm were more likely to experience urinary symptoms. Notably, higher-grade tumors with a Gleason score ≥7 were more commonly observed in men in the finasteride group (37%) versus those in the placebo group (22.2%).2 These findings raised concerns over an increased risk of developing high-grade disease, which prompted the FDA in 2011 to issue guidance against its use for the prevention of prostate cancer.
However, subsequent analysis from the PCPT trial spanning an additional year in length revealed no significant difference in the rates of overall survival after a diagnosis of prostate cancer. Among the entire study population, prostate cancer was identified in 10.5% of men (989/9423) in the finasteride arm and 14.9% of men (1412/9457) in the placebo arm (HR, 0.70; 95% CI, 0.65-0.76; P <.001). Of those diagnoses, 3.5% (n = 333) and 3.0% (n = 286) of patients were classified as having high-grade disease in the finasteride and placebo groups, respectively (relative risk, 1.17; 95% CI, 1.00-1.37; P = .05).3
In this analysis, 5034 deaths occurred—2538 of which were reported in the finasteride group, while 2496 occurred in the placebo group. The 10-year survival rates were 83.0% in the finasteride arm versus 80.9% in the placebo arm for men with low-grade disease and 73.0% versus 73.6%, respectively, for men with high-grade disease. The 15-year survival rates were 78.0% and 78.2% with finasteride and placebo, respectively.
Researchers then paired study participants to the National Death Index, a database of death records overseen by the US Centers for Disease Control Prevention. At a median follow-up of 18.4 years, there were 3048 deaths in the finasteride arm and 2979 deaths in the placebo arm. Forty-two deaths in the finasteride arm and 56 deaths in the placebo arm were attributed to prostate cancer; of those deaths, 18 in the finasteride arm and 20 in the placebo arm were classified by a Gleason score ≥7, revealing no evidence of increased risk of high-grade prostate cancer with finasteride.
“There are significant negative consequences to patients’ health and quality of life that can result from prostate cancer treatment, as well as to their finances and their peace of mind,” said Thompson. “If we can save people from surgeries, and scores of examinations and tests, and spare them from living for years with fear, we should. The best-case scenario for patients is prevention, and this trial has found an inexpensive medication that gets us there.”