Long-term outcomes of localized prostate cancer arising in patients taking 5-ARIs

About one in eight men will be diagnosed with prostate cancer, the second leading cause of cancer-related death in men in the United States. Preventing prostate cancer would dramatically reduce the physical and emotional burden faced by patients and families and the financial burden on the health care system. However, no medications are currently approved for prostate cancer prevention. The 5-α reductase inhibitors (5-ARIs) finasteride and dutasteride are the most promising drugs to date, but also the most controversial. In Canada, 5-ARIs are approved for treating benign prostatic hyperplasia. Although they have been found to reduce prostate cancer risk by about 25%, they are not approved for the prevention of prostate cancer as they have been associated with the development of high-grade prostate cancer. However, whether prior 5-ARI use increases mortality in patients with a diagnosis of prostate cancer remains unclear.To examine this issue, a study by investigators at Princess Margaret Hospital in Toronto, Ontario examined the association of 5-ARI use prior to a prostate cancer diagnosis with survival outcomes in patients with long-term follow-up and detailed pathological information.The population-based cohort study was conducted over a 14-year period in men aged 65 years or older in Ontario, who developed clinically localized prostate cancer and were treated with radiation therapy, active surveillance, androgen deprivation therapy or radical prostatectomy. Patients were classified as 5-ARI users if they had more than one 5-ARI prescription filled prior to their prostate cancer diagnosis. The primary outcomes in the study were overall mortality and prostate cancer-specific mortality. Results showed the following:The cohort included 19,938 patients with prostate cancer. Of these, 2,112 (10.6%) were 5-ARI users and 17,826 (89.4%) were nonusers. During a median follow-up of 8.96 years, 6,053 (30.4%) died, including 1,047 (5.3%) from prostate cancer. 5-ARI use appeared to be associated with increased overall and prostate cancer-specific mortality in crude analyses. However, after inverse probability treatment weights were applied, 5-ARI use was not associated with overall mortality (hazard ratio, 0.98; 95%CI, 0.90–1.07; p=0.77) or prostate cancer-specific mortality (hazard ratio, 1.02; 95%CI, 0.83–1.25; p=0.84); this observation held after multiple sensitivity analyses.The authors conclude that in this large population-based cohort study, 5-ARI use prior to a prostate cancer diagnosis was not associated with prostate cancer-specific or all-cause mortality. The authors believe that their study offers reassuring safety data for patients using 5-ARIs for benign prostatic hyperplasia (approved) or prostate cancer chemoprevention (off-label) indications. Reference:Hamilton RJ, Chavarriaga J, Khurram N, et al. 5-α Reductase inhibitors and prostate cancer mortality. JAMA Network Open 2024;7(8):e2430223. (accessed August 29, 2024).

Long-term outcomes of localized prostate cancer arising in patients taking 5-ARIs

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