All medical care should seek to achieve one or more of three goals: to relieve suffering, to prevent future suffering, or to prolong life. Care for cancer is no exception, and minimizing suffering from cancer and prolonging life has primarily resulted from advances in treatment. Although there are a few notable exceptions, neither primary nor secondary prevention (screening) has had much impact on the morbidity and mortality of cancer.
Prostate cancer is a logical target for a preventive service, and one of the few cancers for which both primary and secondary prevention seems attainable. However, results from screening efforts have been disappointing.
The multicenter Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial1 conducted in the United States showed a non–statistically significant increase in prostate cancer mortality, though the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial2 showed a statistically significant absolute reduction of 0.10 prostate cancer deaths per 1,000 person-years after a median follow-up of 11 years. All-cause mortality was 19.1% in the screened group and 19.3% in the control group—a difference that was not statistically significant.
Much of the morbidity resulting from prostate cancer is a consequence of the diagnosis and management of the disease, rather than the disease itself. Unfortunately, the small reduction in prostate cancer mortality that was seen in the ERSPC occurred in the context of a significant increase in the number of cancers diagnosed and treated in the screened group.
Safe and effective primary prevention of any cancer has much appeal. The Prostate Cancer Prevention Trial (PCPT)3 was a landmark study that sought to reduce the morbidity and mortality of prostate cancer by use of finasteride to prevent development of the disease—ie, primary prevention. Men in both the finasteride and placebo groups were regularly screened for prostate cancer.
Previously published results from this trial showed that the risk of prostate cancer in the finasteride group was 24.8% lower than the placebo group, but the risk of high-grade cancer was 26.9% higher. Several biases have been identified to explain the increase in high-grade cancers,4 but concern for harm remained. In addition, the impact of the reduction in the overall incidence of prostate cancer on morbidity and mortality was uncertain.
Thompson et al recently reported long-term all-cause mortality in study participants,5 and the results were both reassuring and disappointing. If the increase in high-grade cancers had been real rather than the result of diagnostic bias, then one would have anticipated a higher rate of mortality in the finasteride group. In this regard, the results were reassuring, with an overall 15-year mortality rate of 22% in the finasteride group and 21.8% in the control group.
The investigators were unable to report prostate cancer-specific mortality, and as noted in the results of the ERSPC above, a small difference in prostate cancer mortality can exist in the absence of a difference in all-cause mortality. On the other hand, the large overall reduction in prostate cancer incidence should have resulted in a reduction in mortality if these cancers were indeed a significant threat to the health of those diagnosed. In this regard the results were disappointing.
Is there a role for finasteride in the primary prevention of prostate cancer? The safest conclusion is that it has no short- or long-term effect on all-cause mortality; we cannot recommend its use to prolong life. However, one of the major problems with efforts to screen for prostate cancer is overdiagnosis, the diagnosis and treatment of cancers that would never become apparent in the lifetime of the patient in the absence of screening. In a population of men being actively screened for prostate cancer, finasteride does appear to reduce the likelihood of the diagnosis of cancer, and thus reduce the harm associated with overdiagnosis and overtreatment. This reduction has no impact on all-cause mortality. Whether it has either a positive or negative effect on prostate cancer-specific mortality remains unknown, but either way, the effect is likely very small.
A safe and effective approach to both primary and secondary prevention of prostate cancer remains elusive. Screening has at most a small benefit and significant harm. Primary prevention with finasteride likely has no significant impact on mortality, but may reduce the iatrogenic harm that results from screening. We all hope science will move us forward in both areas. ■
Dr. LeFevre is Future of Family Medicine Professor and Vice Chair, Department of Family and Community Medicine, University of Missouri, Columbia.
Disclosure: Dr. LeFevre reported no potential conflicts of interest.
1. Andriole GL, Crawford ED, Grubb RL III, et al: Prostate cancer screening in the randomized prostate, lung, colorectal, and ovarian cancer screening trail: Mortality results after 13 years of follow-up. J Natl Cancer Inst 104:125-132, 2012.
2. Schröder FH, Hugosson J, Roobol MJ, et al: Prostate cancer mortality at 11 years of follow-up. N Engl J Med 366:981-990, 2012.
3. Thompson IM, Goodman PJ, Tangen CM, et al: The influence of finasteride on the development of prostate cancer. N Engl J Med 349:215-224, 2003.
4. Redman MW, Tangen CM, Goodman PJ, et al: Finasteride does not increase the risk of high-grade prostate cancer: A bias-adjusted modeling approach. Cancer Prev Res 1:174-181, 2008.
5. Thompson IM Jr, Goodman PJ, Tangen CM, et al: Long-term survival of participants in the Prostate Cancer Prevention Trial. N Engl J Med 369:603-610, 2013.
In the Prostate Cancer Prevention Trial (PCPT), initially reported in 2003, finasteride significantly reduced the risk of prostate cancer by 24.8% but was associated with a relative 26.9% increase in risk of high-grade disease compared with placebo. In a study reported in The New England Journal of ...