The Efficacy and Safety of Long-term Use of 5-alpha-reductase Inhibitors for Preventing Progression in Prostate Cancer Patients on Active Surveillance – Editorial

Active surveillance (AS) is an alternative to definitive therapy for patients with the National Comprehensive Cancer Network very low-risk, low-risk, and favorable intermediate-risk prostate cancer.1 However, 20% to 30% of AS patients will grade progress on follow-up biopsy or undergo treatment within five years.2-5 Prevention of grade progression in AS patients would decrease treatment incidence, reduce costs of care, and improve health-related quality of life in men on active surveillance.

5-alpha-reductase inhibitor (5ARI) therapy is one potential intervention to prevent progression in AS patients. Robust data demonstrate that 5ARIs diminish grade progression and the use of definitive treatment in AS patients.6 Nevertheless, the U.S. Food and Drug Administration black box label warning of possible risks of the incident high-grade disease remains, and the use of 5ARIs in men on AS to prevent progression has not been widely embraced. 

These investigators performed a single-center cohort study of 288 AS patients (1995–2016) comparing non-5ARI users (n = 203) to 5-ARI users to further investigate 5ARI efficacy and safety in this population. Median follow-up was seven years. The primary endpoint was pathologic progression, defined as an increased grade, an increased number of cores to > 3, or any core involvement > 50% in follow-up biopsies. Other outcomes included grade progression; volume progression, defined as an increase in the number of positive cores to > 3 or any core involvement to > 50%; and progression to definitive treatment. They observed that non-5ARI users had higher risks of pathologic (56% vs 28%, p < 0.001), grade (40 % vs 22%, p = 0.003) volume (51% vs 27%, p < 0.001), and definitive treatment (51% vs 27%, p = 0.001) progression. Moreover, the frequency of progression to high-grade (Grade Group 3/4) tumors was low and did not significantly differ between the non-5ARI and 5 ARI groups (4% versus 2%, p = 0.40).

The take-home message: these results validate a robust and expanding body of Level 1 and 2 data supporting the efficacy and safety of 5ARIs to prevent grade progression in AS patients. Consideration may be given to 5ARI therapy in this patient population to reduce the risks of prevention and treatment. 

Written by: J. Kellogg Parsons, MD, MHS, Urologist, Professor of Urology, University of California San Diego Health, San Diego, California

References:

1. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf
2. Bul, Meelan, Xiaoye Zhu, Riccardo Valdagni, Tom Pickles, Yoshiyuki Kakehi, Antti Rannikko, Anders Bjartell et al. "Active surveillance for low-risk prostate cancer worldwide: the PRIAS study." European urology 63, no. 4 (2013): 597-603.
3. Klotz, Laurence, Danny Vesprini, Perakaa Sethukavalan, Vibhuti Jethava, Liying Zhang, Suneil Jain, Toshihiro Yamamoto, Alexandre Mamedov, and Andrew Loblaw. "Long-term follow-up of a large active surveillance cohort of patients with prostate cancer." Journal of Clinical Oncology 33, no. 3 (2015): 272-277.
4. Tosoian, Jeffrey J., Bruce J. Trock, Patricia Landis, Zhaoyong Feng, Jonathan I. Epstein, Alan W. Partin, Patrick C. Walsh, and H. Ballentine Carter. "Active surveillance program for prostate cancer: an update of the Johns Hopkins experience." J Clin Oncol 29, no. 16 (2011): 2185-2190.
5. Fleshner, Neil E., M. Scott Lucia, Blair Egerdie, Lorne Aaron, Gregg Eure, Indrani Nandy, Libby Black, and Roger S. Rittmaster. "Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial." The Lancet 379, no. 9821 (2012): 1103-1111.
6. Finelli, Antonio, Greg Trottier, Nathan Lawrentschuk, Robert Sowerby, Alexandre R. Zlotta, Lenny Radomski, Narhari Timilshina et al. "Impact of 5α-reductase inhibitors on men followed by active surveillance for prostate cancer." European urology 59, no. 4 (2011): 509-514.

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