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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.

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Fig. 1: Pathologic progression in the 5ARI vs. non-5ARI group.

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Finelli, A., Komisarenko, M., Martin, L.J. et al. Long-term use of 5-alpha-reductase inhibitors is safe and effective in men on active surveillance for prostate cancer. Prostate Cancer Prostatic Dis 24, 69–76 (2021). https://doi.org/10.1038/s41391-020-0218-2

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