TO THE EDITOR:
One man in nine will receive a diagnosis of prostate cancer during his lifetime. We previously reported the results of the Prostate Cancer Prevention Trial, in which 18,882 men were randomly assigned to receive finasteride or placebo for 7 years. The study’s primary end point — the prevalence of prostate cancer during the 7 years of the trial — was met: the relative risk of prostate cancer with finasteride was 24.8% lower than the risk with placebo.1 Paradoxically, the risk of high-grade cancer (Gleason score of 7 to 10) was higher with finasteride, a finding that led to recommendations against the use of finasteride for the prevention of prostate cancer. Subsequent trials showed that finasteride improved detection of prostate cancer and high-grade prostate cancer by improving the performance characteristics of the prostate-specific antigen (PSA) test, digital rectal examination, and the prostate biopsy. These biases could explain the paradox, but the questions of whether the greater number of high-grade prostate cancers could have led to diminished survival or to an increase in prostate cancer mortality persisted.2 In 2013, we addressed the first of these questions, finding similar survival rates in the two treatment groups of the Prostate Cancer Prevention Trial.3
To address the second question, participants with a potentially valid Social Security number, whether last known to be alive or previously deceased, were submitted to the National Death Index in December 2014. Deaths from prostate cancer were reviewed by an end-point review committee. The cumulative incidence of death from prostate cancer was calculated, including all participants who underwent randomization, with deaths due to a cause other than prostate cancer classified as a competing risk. (For details, see the Supplementary Appendix, available with the full text of this letter at NEJM.org.)
Figure 1 shows the results. With 296,842 person-years of follow-up and a median follow-up of 18.4 years, of 9423 men randomized to finasteride, there were 3048 deaths of which 42 were due to prostate cancer; of 9457 randomized to placebo, there were 2979 deaths, 56 due to prostate cancer. With the small number of deaths due to prostate cancer, the 25% lower risk of death from prostate cancer with finasteride was not statistically significant.
PSA-detected prostate cancer will likely increase with recommendations to offer screening to men 55 to 65 years of age.4 Screening may reduce the risk of death from prostate cancer but often leads to the detection of prostate cancer that will remain asymptomatic during a man’s life. If indolent cancers are treated with surgery or radiation, complications, including impotence and incontinence, are common. If managed with active surveillance, up to 45% of men will ultimately receive treatment; they will also face frequent examination, repeated invasive biopsies, and anxiety.5 Finasteride is a generic agent that is used to treat lower urinary tract symptoms, prevents complications from these symptoms, and prevents prostate cancer. The early concerns regarding an association between finasteride and an increased risk of high-grade prostate cancer have not been borne out.
Phyllis J. Goodman, M.S.
Catherine M. Tangen, Dr.P.H.
Fred Hutchinson Cancer Research Center, Seattle, WA
Amy K. Darke, M.S.
M. Scott Lucia, M.D.
Leslie G. Ford, M.D.
Lori M. Minasian, M.D.
Howard L. Parnes, M.D.
Michael L. LeBlanc, Ph.D.
Ian M. Thompson, Jr., M.D.
CHRISTUS Santa Rosa Hospital Medical Center, San Antonio, TX
Supported by grants (UM1 CA182883 and U10 CA37429) from the
Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.