Effect of metformin on prostate cancer outcomes after radical prostatectomy

Recent studies have shown a relative risk reduction in the incidence of prostate cancer in patients taking metformin. However, there are conflicting findings on the effect of metformin on established cases of prostate cancer. In this study we evaluated the effect of metformin on survival and pathologic outcomes in established prostate cancer.

We retrospectively identified 12,052 patients who underwent radical prostatectomy between 1997 and 2010 at Mayo Clinic. Among these, 885 (7.3%) were diabetics, including 323 taking and 562 not taking metformin. Kaplan-Meier method was utilized to calculate rates of biochemical recurrence (BCR), systemic progression (SP), and all-cause mortality (ACM). Cox models were used to estimate the metformin hazard ratio (HR) adjusted for clinical and pathologic variables.

Median follow-up was 5.1 years. In univariate analysis, metformin HR (95% confidence intervals) was not significant for BCR (1.13 [0.84, 1.52]; P = 0.40), SP (1.37 [0.69, 2.72]; P = 0.37), and ACM (1.32 [0.84, 2.05]; P = 0.23). After adjusting for covariates of interest, the HRs for metformin among diabetics remained nonsignificant for BCR (0.91 [0.67, 1.24]; P = 0.55), SP (0.83 [0.39, 1.74]; P = 0.62); and ACM (1.16 [0.73, 1.86]; P = 0.53). No significant difference was seen between metformin users and nonusers in the final pathologic Gleason score (P = 0.33), stage (P = 0.1), rate of positive surgical margins (P = 0.29), or tumor volume (P = 0.76). Metformin use was not associated with a risk reduction in BCR, SP, or ACM. Besides presenting survival data, our results describing metformin's effect on final pathology are unique.