Long-term use of 5-alpha-reductase inhibitors is safe and effective in men on active surveillance for prostate cancer

Abstract

Background: Although 5-alpha-reductase inhibitors (5ARIs) have been shown to benefit men with prostate cancer (PCa) on active surveillance (AS), their long-term safety remains controversial. Our objective is to describe the long-term association of 5ARI use with PCa progression in men on AS. Materials/subjects and methods: The cohort of men with low-risk PCa was derived from a prospectively maintained AS database at the Princess Margaret (1995–2016). Pathologic, grade, and volume progression were the primary end points. Kaplan–Meier time-to-event analysis was performed and Cox proportional hazards regression was used to determine predictors of progression where 5ARI exposure was analyzed as a time-dependent variable. Patients who came off AS prior to any progression events were censored at that time. Results: The cohort included 288 men with median follow-up of 82 months (interquartile range: 37–120 months). Among non-5ARI users (n = 203); 114 men (56.2%) experienced pathologic progression compared with 24 men (28.2%) in the 5ARI group (n = 85), (p < 0.001). Grade and volume progression were higher in the non-5ARI group compared with the 5ARI group (n = 82; 40.4% vs. n = 19; 22.4% respectively, p = 0.003 for grade progression; n = 87; 43.1% and n = 15; 17.7%, respectively for volume progression p < 0.001). Lack of 5ARI use was independently positively associated with pathologic progression (HR: 2.65; CI: 1.65–4.24), grade progression (HR: 2.75; CI: 1.49–5.06), and volume progression (HR: 3.15; CI: 1.78–5.56). The frequency of progression to high-grade (Grade Group 4–5) tumors was not significantly different between the groups. Conclusions: Use of 5ARIs diminished both grade and volume progression without an increased risk of developing Grade Groups 4–5 disease.