Evidence on 5-ARIs in Patients on Active Surveillance
A goal of Reboot Rx is to provide an educational resource that compiles the available evidence in a single location to support clinicians in making decisions that could help individual patients. This page summarizes published clinical studies evaluating 5-ARIs (dutasteride and finasteride) in men with low-risk (Gleason score 6) or favorable intermediate-risk (Gleason 7 [3+4]) prostate cancer on active surveillance.
5-ARIs are not FDA-approved for patients with prostate cancer. This page is intended for informational purposes only and is not intended to provide medical advice and should not be relied upon in that regard. Clinicians should make individual prescribing decisions for their patients based on the patient's clinical presentation and the clinician’s own medical decision-making.
Evidence Summary:
There are 17 published studies evaluating 5-ARIs in patients with prostate cancer on active surveillance.
2 randomized controlled trials (and 1 subanalysis)
Randomized Controlled Trials
REDEEM: Reduction by Dutasteride of Clinical Progression Events in Expectant Management
Fleshner, et al. Lancet, 20121
REDEEM was a multicenter, randomized, double-blind, placebo-controlled trial evaluating once daily dutasteride (0.5 mg) versus placebo for 3 years in 302 men with Gleason score ≤6 prostate cancer on active surveillance.
Dutasteride delayed pathological or therapeutic disease progression compared with placebo in men with low-risk (99.7% with Gleason score 6) prostate cancer over 3 years (HR 0.62, 95% CI 0.43–0.89, log-rank p = 0.009).
Margel et al., The Journal of Urology, 2013 conducted a subanalysis of the REDEEM dataset and identified that older age (HR 1.05, 95% CI 1.01–1.08, p = 0.009) and higher prostate-specific antigen (PSA) density (HR 1.06, 95% CI 1.04–1.09, p < 0.001) were associated with pathological progression.2
These limitations should be considered when evaluating the data:
Because 5-ARIs can impact PSA values (see Safety), unadjusted PSA values could introduce treatment bias against the placebo group.
Higher-than-expected progression rates in the placebo group. The rates are not aligned with those in other prostate cancer active surveillance studies.
Small study size.
Use of surrogate endpoints might not reflect true disease progression, which can only be confirmed through whole-prostate pathological examination.
Study sponsor: GlaxoSmithKline
MAPPED: Magnetic Resonance Imaging in Primary Prostate Cancer After Exposure to Dutasteride
Moore, et al., Journal of Urology, 20173
MAPPED was a randomized, double-blind, placebo-controlled trial evaluating once daily dutasteride (0.5 mg) versus placebo for 6 months in 42 men with Gleason score ≤7 (3+4) prostate cancer on active surveillance in the UK.
These limitations should be considered when evaluating the data:
Small sample size limits the ability to definitively ascribe findings to the effect of dutasteride.
Short follow-up.
Lack of baseline targeted biopsies to match the targeted exit biopsies limits the ability to definitively ascribe findings to the effect of dutasteride.
The eligibility criteria limits the generalizability of the study population.
Study sponsor: University College London, with financial support from GlaxoSmithKline
FINESSE: Finasteride in Active Surveillance for Men With Low and Intermediate-Risk Prostate Cancer
Cumberbatch, et al., BMJ Open, 20254 (protocol)
The trial opened recruitment in August 2022 and is expected to be completed in March 2028.5
FINESSE is a randomized, phase 3, open-label trial evaluating daily finasteride (5 mg for 2 years) aiming to recruit 550 men with Gleason score ≤7 (3+4) prostate cancer on active surveillance in the UK. Participants will be monitored in outpatient follow-up for 3-5 years, followed by passive registry-based follow-up for ≤10 years.
These limitations should be considered when evaluating the data:
Pre-biopsy MRI eligibility may reduce the pool of eligible participants and affect recruitment.
Pharmacologic manipulation of PSA may influence clinical decision-making during active surveillance.
Study sponsor: Sheffield Teaching Hospitals NHS Foundation Trust; coordinated by Cancer Research UK and the Cancer Prevention Trials Unit at Queen Mary University of London. Funded by Yorkshire Cancer Research.
Meta-Analyses
Note that limitations to these meta-analyses include variation in definitions of progression and follow-up duration across included studies. All three meta-analyses were performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The authors of each meta-analysis suggest that additional studies evaluating 5-ARI use for patients with prostate cancer would be beneficial.
Luo et al., Asian Journal of Andrology, 20206
This meta-analysis evaluated 5-ARI exposure on prostate cancer incidence or progression. The search included studies published up to July 2018. Two studies (590 men) specifically examined progression among 5-ARI users compared with non-users during active surveillance. In this subgroup of studies, the pooled relative risk for progression in men with low-risk prostate cancer using 5-ARIs versus non-users was 0.58 (95% CI 0.43–0.78, p < 0.001). No pooled safety analysis was performed.
Deng et al., Peer J, 20207
This meta-analysis assessed 10 studies (2,277 men) through October 2019 that compared prognostic outcomes in 5-ARI users after diagnosis versus non-users. 5-ARI use was associated with a longer progression-free survival (HR 0.57, 95% CI 0.34–0.96, p = 0.04) and reduction in total progression (OR 0.61, 95% CI 0.48–0.77, p < 0.0001), especially for patients with localized disease (OR 0.56, 95% CI 0.44–0.73, p < 0.00001) and Gleason scores ≤7 (OR 0.63, 95% CI 0.48–0.84, p = 0.002). The pooled analysis found no significant difference in the occurrence of reported side effects between 5-ARI users and non-users (OR 1.01, 95% CI 0.68–1.50, p = 0.95). Because the included studies enrolled broader prostate cancer populations (not exclusively men on active surveillance), some findings may not directly reflect outcomes specific to active surveillance cohorts.
Matsukawa et al., European Urology Oncology, 20248
This meta-analysis synthesized evidence on nonsurgical interventions that may delay disease progression in men on active surveillance for prostate cancer. This review included 22 studies published through June 2023, of which 7 (2,985 men) specifically focused on 5-ARI use during active surveillance. The authors concluded that 5-ARI use reduces the risk of progression compared to active surveillance alone (pooled HR 0.59, 95% CI 0.48–0.72, p < 0.001). Safety results were drawn from the REDEEM trial, which reported no differences in treatment-related adverse events between groups. The authors reported higher rates of sexual adverse events or breast disorders in the dutasteride group.
Observational Studies
Ten observational studies have evaluated 5-ARI use in men with prostate cancer on active surveillance. Some studies suggest improved outcomes in clinical practice, while other studies suggest no significant difference in outcomes. Patients in these studies were prescribed 5-ARIs mainly for benign prostatic hyperplasia and urinary tract symptoms. As with all observational research, these studies can identify associations but cannot establish causality, and findings may be influenced by confounding factors, such as treatment selection bias.
Finasteride is available in a 1 mg formulation, which is FDA-approved for androgenic alopecia. 1 mg finasteride has not been studied in a randomized controlled trial or evaluated by the FDA for use in patients with prostate cancer.
References:
1. Fleshner NE, et al. Lancet. 2012;379(9821):1103–11. 2. Margel D, et al. J Urol. 2013;190(6):2039–45. 3. Moore CM, et al. J Urol. 2017;197(4):1006–13. 4. Cumberbatch M, et al. BMJ Open. 2025;15(2):e096431. 5. ISRCTN Registry. Finasteride Evaluation in Active Surveillance for Low and Intermediate-Risk Prostate Cancer (ISRCTN16867955). Randomized Phase III Trial of Finasteride in Active Surveillance. Registered August 27, 2021. Accessed January 9, 2026. https://www.isrctn.com/ISRCTN16867955 6. Luo LM, et al. Asian J Androl. 2020;22(5):532–8. 7. Deng T, et al. PeerJ. 2020;8:e9282. 8. Matsukawa A, et al. Eur Urol Oncol. 2024;7(3):376–400. 9. Finelli A, et al. Prostate Cancer Prostatic Dis. 2021;24(1):69–76. 10. Ashrafi AN, et al. World J Urol. 2021;39(9):3295–3307. 11. Kearns JT, et al. J Urol. 2019;201(1):106–11. 12. Özkan TA, et al. Turk J Urol. 2018;44(2):132–7. 13. Dai C, et al. J Urol. 2018;199(2):445–52. 14. Shelton PQ, et al. Urology. 2013;81(5):979–84. 15. Chiang AS, et al. Can Urol Assoc J. 2013;7(11-12):450–3. 16. Ross AE, et al. BJU Int. 2012;110(5):651–7. 17. Finelli A, et al. Eur Urol. 2011;59(4):509–14. 18. Barqawi AB, et al. Urology. 2010;76(5):1067–71.
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