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



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.


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.


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.


  1. Tosoian JJ, Carter HB, Lepor A, Loeb S. Active surveillance for prostate cancer: current evidence and contemporary state of practice. Nat Rev Urol. 2016;13:205–15.

    Article  Google Scholar 

  2. Cooperberg MR. Active Surveillance for low-risk prostate cancer—an evolving international standard of care. JAMA Oncol. 2017;3:1398–9.

    Article  Google Scholar 

  3. Klotz L, Vesprini D, Sethukavalan P, Jethava V, Zhang L, Jain S, et al. Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. J Clin Oncol. 2015;33:272–7.

    Article  Google Scholar 

  4. Tosoian JJ, Trock BJ, Landis P, Feng Z, Epstein JI, Partin AW, et al. Active surveillance program for prostate cancer: an update of the Johns Hopkins experience. J Clin Oncol. 2011;29:2185–90.

    Article  Google Scholar 

  5. Tosoian JJ, Mamawala M, Epstein JI, Landis P, Wolf S, Trock BJ, et al. Intermediate and longer-term outcomes from a prospective active-surveillance program for favorable-risk prostate cancer. J Clin Oncol. 2015;33:3379–85.

    Article  Google Scholar 

  6. Bruinsma SM, Bangma CH, Carroll PR, Leapman MS, Rannikko A, Petrides N, et al. Active surveillance for prostate cancer: a narrative review of clinical guidelines. Nat Rev Urol. 2016;13:151–67.

    CAS  Article  Google Scholar 

  7. Loeb S. Active surveillance offers functional advantages without impacting survival for low-risk prostate cancer. Eur Urol. 2018;73:868–9.

    Article  Google Scholar 

  8. Loeb S, Folkvaljon Y, Curnyn C, Robinson D, Bratt O, Stattin P. Uptake of active surveillance for very-low-risk prostate cancer in Sweden. JAMA Oncol. 2017;3:1393–8.

    Article  Google Scholar 

  9. Komisarenko M, Timilshina N, Richard PO, Alibhai SM, Hamilton R, Kulkarni G, et al. Stricter active surveillance criteria for prostate cancer do not result in significantly better outcomes: a comparison of contemporary protocols. J Urol. 2016;196:1645–50.

    Article  Google Scholar 

  10. Wong LM, Ferrara S, Alibhai SM, Evans A, Van der Kwast T, Trottier G, et al. Diagnostic prostate biopsy performed in a non-academic center increases the risk of re-classification at confirmatory biopsy for men considering active surveillance for prostate cancer. Prostate Cancer Prostatic Dis. 2015;18:69–74.

    CAS  Article  Google Scholar 

  11. Wong LM, Trottier G, Toi A, Lawrentschuk N, Van der Kwast TH, Zlotta A, et al. Should follow-up biopsies for men on active surveillance for prostate cancer be restricted to limited templates? Urology. 2013;82:405–9.

    CAS  Article  Google Scholar 

  12. Weiss B, Loeb S. Standard and targeted biopsy during follow-up for active surveillance. Rev Urol. 2015;17:112–3.

    PubMed  PubMed Central  Google Scholar 

  13. Violette PD, Saad F. Chemoprevention of prostate cancer: myths and realities. J Am Board Fam Med. 2012;25:111–9.

    Article  Google Scholar 

  14. Vemana G, Hamilton RJ, Andriole GL, Freedland SJ. Chemoprevention of prostate cancer. Annu Rev Med. 2014;65:111–23.

    CAS  Article  Google Scholar 

  15. Richard PO, Finelli A. 5-Alpha reductase inhibitors in active surveillance. Curr Opin Urol. 2014;24:324–8.

    Article  Google Scholar 

  16. Jayalath VH, Nayan M, Finelli A, Komisarenko M, Timilshina N, Kulkarni GS, et al. Statin use and time to progression in men on active surveillance for prostate cancer. Prostate Cancer Prostatic Dis. 2018;21:509–15.

    CAS  Article  Google Scholar 

  17. Finelli A, Trottier G, Lawrentschuk N, Sowerby R, Zlotta AR, Radomski L, et al. Impact of 5alpha-reductase inhibitors on men followed by active surveillance for prostate cancer. Eur Urol 2011;59:509–14.

    CAS  Article  Google Scholar 

  18. Shelton PQ, Ivanowicz AN, Wakeman CM, Rydberg MG, Norton J, Riggs SB, et al. Active surveillance of very-low-risk prostate cancer in the setting of active treatment of benign prostatic hyperplasia with 5alpha-reductase inhibitors. Urology. 2013;81:979–84.

    Article  Google Scholar 

  19. Ross AE, Feng Z, Pierorazio PM, Landis P, Walsh PC, Carter HB, et al. Effect of treatment with 5-alpha reductase inhibitors on progression in monitored men with favourable-risk prostate cancer. BJU Int. 2012;110:651–7.

    CAS  Article  Google Scholar 

  20. Vidal AC, Howard LE, Moreira DM, Castro-Santamaria R, Andriole GL, Freedland SJ. Aspirin, NSAIDs, and risk of prostate cancer: results from the REDUCE study. Clin Cancer Res. 2015;21:756–62.

    CAS  Article  Google Scholar 

  21. Wong LM, Fleshner N, Finelli A. Impact of 5-alpha reductase inhibitors on men followed by active surveillance for prostate cancer: a time-dependent covariate reanalysis. Eur Urol. 2013;64:343.

    CAS  Article  Google Scholar 

  22. Babaian RJ, Toi A, Kamoi K, Troncoso P, Sweet J, Evans R, et al. A comparative analysis of sextant and an extended 11-core multisite directed biopsy strategy. J Urol. 2000;163:152–7.

    CAS  Article  Google Scholar 

  23. Fleshner NE, Lucia MS, Egerdie B, Aaron L, Eure G, Nandy I, et al. Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial. Lancet. 2012;379:1103–11.

    CAS  Article  Google Scholar 

  24. Dai C, Ganesan V, Zabell J, Nyame YA, Almassi N, Greene DJ, et al. Impact of 5alpha-reductase inhibitors on disease reclassification among men on active surveillance for localized prostate cancer with favorable features. J Urol. 2018;199:445–52.

    CAS  Article  Google Scholar 

  25. Komisarenko M, Wong LM, Richard PO, Timilshina N, Toi A, Evans A, et al. An increase in gleason 6 tumor volume while on active surveillance portends a greater risk of grade reclassification with further followup. J Urol. 2016;195:307–12.

    Article  Google Scholar 

  26. Iremashvili V, Pelaez L, Manoharan M, Jorda M, Rosenberg DL, Soloway MS. Pathologic prostate cancer characteristics in patients eligible for active surveillance: a head-to-head comparison of contemporary protocols. Eur Urol. 2012;62:462–8.

    Article  Google Scholar 

  27. Andriole GL, Bostwick D, Brawley OW, Gomella L, Marberger M, Montorsi F, et al. The effect of dutasteride on the usefulness of prostate specific antigen for the diagnosis of high grade and clinically relevant prostate cancer in men with a previous negative biopsy: results from the REDUCE study. J Urol. 2011;185:126–31.

    CAS  Article  Google Scholar 

  28. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349:215–24.

    CAS  Article  Google Scholar 

  29. Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010;362:1192–202.

    CAS  Article  Google Scholar 

  30. Unger JM, Hershman DL, Till C, Tangen CM, Barlow WE, Ramsey SD, et al. Using Medicare claims to examine long-term prostate cancer risk of finasteride in the prostate cancer prevention trial. J Natl Cancer Inst. 2018.

  31. Preston MA, Wilson KM, Markt SC, Ge R, Morash C, Stampfer MJ, et al. 5Alpha-reductase inhibitors and risk of high-grade or lethal prostate cancer. JAMA Intern Med. 2014;174:1301–7.

    Article  Google Scholar 

  32. Wallerstedt A, Strom P, Gronberg H, Nordstrom T, Eklund M. Risk of prostate cancer in men treated with 5alpha-reductase inhibitors—a Large Population-Based Prospective Study. J Natl Cancer Inst. 2018;110:1216–21.

    Article  Google Scholar 

  33. Kulkarni GS, Lockwood G, Evans A, Toi A, Trachtenberg J, Jewett MA, et al. Clinical predictors of Gleason score upgrading: implications for patients considering watchful waiting, active surveillance, or brachytherapy. Cancer. 2007;109:2432–8.

    Article  Google Scholar 

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Correspondence to A. Finelli.

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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).

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