ACTIVE surveillance (AS) remains a key approach in managing low-risk prostate cancer (PCa), involving careful monitoring with the goal of initiating treatment only if significant disease progression occurs. Eligibility for AS typically includes low-risk patients, characterised by factors such as a low Gleason score, low PSA levels, and limited core involvement. Metformin, a well-known oral hypoglycemic agent used primarily for diabetes management, has shown promise in preclinical studies suggesting potential anti-cancer properties, including slowing PCa progression. However, its impact on patients undergoing AS for low-risk PCa has not been fully evaluated.
This study investigates the effect of metformin on progression rates among men with low-risk localised PCa on AS through a randomised, double-blind, placebo-controlled trial conducted across 14 centres in Canada. Patients with biopsy-confirmed, low-risk PCa diagnosed within the previous six months, with a Gleason score of <6, a PSA level of ≤10 ng/ml, and a clinical stage of T1c-T2a, were eligible. These patients, who opted for AS, were randomly assigned (1:1) to receive either metformin 850 mg twice daily or a placebo for three years. Repeat prostate biopsies were conducted at 18 and 36 months to monitor progression, with disease progression defined as the initiation of primary PCa treatment or pathological progression based on core involvement and Gleason score.
Among 407 participants, 204 received metformin and 203 received placebo. The median age of the cohort was 63 years. Disease progression occurred in 141 patients, with no statistically significant difference in progression-free survival (PFS) between the metformin and placebo groups (p=0.63).
In conclusion, despite promising preclinical and epidemiological data, metformin does not appear to impact disease progression in men with low-risk PCa on AS. Further research is needed to explore alternative strategies for managing low-risk PCa.
Katie Wright, EMJ
Reference
Fleshner NE et al. A randomized, double-blind, placebo-controlled trial of metformin in reducing progression among men on expectant management for low-risk prostate cancer: The MAST (Metformin Active Surveillance Trial) study. Abstract LBA5002. ASCO 2024, May 31-June 4, 2024.
