Protective Effects of Metformin Against Biochemical Failure Following Radical Prostatectomy or Radiation Therapy in...

To assess the impact of metformin on biochemical failure (BF) in localized prostate cancers (PC) treated with radical prostatectomy or radiation therapy.

About 1449 patients undergoing radical prostatectomy (n = 1338, 92.3%) or radiation therapy (n = 108, 7.5%) for localized PC between July 2007 and January 2020 were evaluated for metformin use, demographic/oncologic characteristics, and biochemical outcomes. Androgen deprivation therapy was utilized per NCCN guidelines. BF rates were assessed overall and at 1, 3, and 5 years. Time to BF was estimated via Kaplan-Meier; logistic regression and Cox proportionate hazards models were generated to adjust for significant differences.

Of 1449 patients, 148 (10.2%) utilized metformin at time of diagnosis, while 1,301 (89.8%) did not. Patients on metformin were significantly older, had higher body mass indexes, and more aggressive disease (Gleason score >7). At a mean ± SD follow-up of 3.6 ± 2.6 years, patients on metformin were less likely to experience BF at later timepoints; however, univariate analysis showed no differences at 1, 3, and 5 years. In multivariate analysis, patients on metformin were significantly less likely to experience BF at 5 years and overall in both treatment groups. In Cox regression, metformin was independently associated with a 40% relative risk reduction in BF.

In multivariate analysis, metformin use was associated with a significant risk reduction in BF overall and at 5 years following primary treatment; this trend was not witnessed in univariate analysis. This suggests the need for future investigations of metformin's role in disease-free survival in men with localized PC.