A recent follow-up study in the New England Journal of Medicine(www.nejm.org) (NEJM) upheld findings from a previous trial that indicated finasteride therapy could reduce the overall risk of prostate cancer in men who received regular screening for the disease. The current study also was able to dispel concerns raised by the earlier research about the potential for increased mortality associated with finasteride use.
Specifically, the NEJM study confirmed results from the Prostate Cancer Prevention Trial (PCPT) conducted from January 1997 to February 2003 that showed finasteride use substantially reduced the overall relative risk of prostate cancer in men undergoing regular screening for the disease compared with placebo. Of concern in that earlier study, however, was an observed relative increase in the number of high-grade cancers diagnosed in men taking finasteride. Based on that finding, the NEJM study sought to determine whether there was evidence of a greater risk of death among men in the finasteride group compared with those in the placebo group.
What the Previous Research Found
Nearly 25,000 men enrolled in the PCPT, and 18,882 underwent randomization; most of those who were not randomized had a prostate-specific antigen (PSA) level of more than 3.0 ng per mL. After a three-month run-in period of taking daily placebo, men whose PSA levels were 3.0 ng per mL or lower and who met adherence and tolerance criteria were randomized to receive either 5 mg finasteride (Proscar) or placebo daily.
- A recent New England Journal of Medicine study builds on earlier research and indicates finasteride could reduce some of the risks, such as overdetection, associated with prostate-specific antigen (PSA)-based screening.
- Although use of the drug was associated with a modestly increased risk of high-grade prostate cancer, it significantly reduced the risk of low-grade prostate tumors and led to no short- or long-term effect on all-cause mortality.
- Men who are aware of and understand the benefits, risks and uncertainties associated with the use of finasteride for prostate cancer prevention may make a rational decision to take the drug to reduce the potential harms of PSA screening.
All participants were screened annually using digital rectal examination and PSA testing. Biopsies were recommended during the trial in men who experienced an elevated PSA level, an abnormal digital rectal examination, or both.
Of the 9,060 men who were included in the final analysis, prostate cancer was detected in 803 of the 4,368 in the finasteride group (18.4 percent) and 1,147 of the 4,692 in the placebo group (24.4 percent), for a relative risk reduction of 24.8 percent. High-grade disease was seen in 6.4 percent of men in the finasteride group versus 5.1 percent in the control group.
According to authors of the NEJM study, despite subsequent analyses that indicated finasteride "improved the sensitivity of PSA testing, prostate biopsy, and digital rectal examination for the detection of prostate cancer and improved the sensitivity of PSA testing and prostate biopsy for the detection of high-grade disease," the increased rate of high-grade tumors seen in PCPT participants who took the drug "all but eliminated the use of finasteride for prostate cancer prevention."
What the Current Study Adds
Conducted 18 years after the first PCPT participant was randomized, the NEJM follow-up study found that the increased risk of high-grade cancer seen with finasteride use led to no short- or long-term effect on all-cause mortality in PCPT participants, with no difference in survival rates seen among the two groups. Furthermore, finasteride continued to significantly reduce the risk of the low-grade prostate tumors that lead to much of the overdetection (and subsequent harm) that served as a basis for the U.S. Preventive Services Task Force's (USPSTF's) 2012 recommendation against PSA testing(www.uspreventiveservicestaskforce.org), said researchers.
"Although the prevention of these (low-grade) tumors did not appear to reduce overall mortality, increased diagnosis of low-grade prostate cancer is a problematic by-product 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," the study authors concluded.
Because much of the morbidity resulting from prostate cancer is a consequence of diagnosis and management of disease, rather than the disease itself, the AAFP, along with the USPSTF and many other organizations, have recommended against PSA screening to one degree or another. Regardless, an estimated 40 percent to 50 percent of men ages 50 years and older undergo screening each year(www.ncbi.nlm.nih.gov).
What It All Means
It is to this group of patients -- and their physicians -- that the NEJM study may offer the greatest benefit, said family physician and USPSTF Co-vice Chair Michael LeFevre, M.D., M.S.P.H. in an accompanying editorial(www.nejm.org).
"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," LeFevre said in the editorial. "Whether the use of the drug has either a positive or a negative effect on prostate cancer-specific mortality remains unknown, but either way, the effect is probably very small and does not result in any difference in life expectancy.
"Men who are aware of and understand the benefits, risks, and uncertainties associated with the use of finasteride for prevention may make a rational decision to take the drug to reduce the harm of screening. Of course, another way to reduce the harm of screening is to choose not to be screened."