Metformin Active Surveillance Trial in Low-Risk Prostate Cancer

Abstract

Purpose

Active surveillance (AS) is a standard management strategy for low-risk prostate cancer (PCa), but a significant proportion of patients ultimately experience disease progression. Metformin, a commonly prescribed antidiabetic agent, has demonstrated antitumor activity in preclinical studies and observational data, prompting investigation into its potential to delay PCa progression.

Patients and Methods

The Metformin Active Surveillance Trial (MAST) was a multicenter, randomized, double-blind, placebo-controlled phase III trial evaluating the efficacy of metformin in men with low-risk, localized PCa managed with AS. Eligible participants were randomly assigned 1:1 to receive either metformin (850 mg twice daily) or placebo and were followed for up to 36 months. The primary end point was time to progression, defined as therapeutic and/or pathologic progression. Progression-free survival (PFS) was assessed using Kaplan-Meier analysis and Cox proportional hazards models.

Results

A total of 408 patients were randomly assigned (205 metformin, 203 placebo). After a median follow-up of 36 months, 144 participants experienced progression (70 metformin, 74 placebo), with no significant difference in PFS (hazard ratio [HR], 1.09 [95% CI, 0.79 to 1.52]; P = .59). Negative biopsy rates at 36 months were 41.0% (metformin) versus 31.1% (placebo; P = .181). In prespecified subgroup analysis, metformin was associated with increased pathologic progression among obese patients (BMI ≥ 30; HR, 2.36 [95% CI, 1.21 to 4.59]; P = .0092).

Conclusion

Metformin did not reduce progression in men with low-risk PCa on AS. The observed adverse effect in obese patients merits further investigation.

Neil E. Fleshner et al. Metformin Active Surveillance Trial in Low-Risk Prostate Cancer. J Clin Oncol 43, 3662-3671(2025).

DOI:10.1200/JCO-25-01070