The effect of metformin on cancer-specific survival outcomes in diabetic patients undergoing radical cystectomy for urothelial carcinoma of the bladder

Purpose: Metformin, a first-line oral therapy for diabetes, has anticancer properties. Our objective was to evaluate the association between metformin use and oncologic outcomes in diabetic patients undergoing radical cystectotny (RC) for bladder cancer (BC). Methods: A single-institution retrospective cohort (January 1997 June 2013) of diabetic patients undergoing RC was assembled. Medication use was assessed at time of surgery. Outcome measures were recurrence-free survival (RFS). BC-specific survival (BCSS), and overall survival (OS). Multivariable Cox proportional hazards models were used. To create parsimonious models, the change of estimate approach (10% threshold) was used as a variable selection strategy for final model inclusion separately for each outcome measure. Results: Of 421 patients, 85 (20%) had diabetes. There were 39 (46%) patients on metformin therapy. Among diabetic patients, there were 21 patients with BC recurrence, 16 who died of BC, and 30 who died overall. In univariate analyses, metformin use among diabetic patients was associated with improved RFS (hazard ratio = 0.54, 95% Cl: 0.33 (1.88, P = 0.013) and trended toward improved BCSS (hazard ratio = 0.65, 95% Cl: 0.40-1.07, P = 1.087), but not with OS (P = 0.87). In multivariable models, metformin use among diabetic patients was associated with significantly improved RFS (adjusted hazard ratio = 0.38, 95% CI: 0.20-0.72, P = 0.003) and BCSS (adjusted hazard ratio = 0.57, 95% Cl: 0.35-0.91, P = 0.019), but not with OS (P = 0.89). Use of other oral hypoglycemic agents or insulin was not associated with oncologic outcomes. Conclusions: Our study is among the first to report an association between metformin use and improved RFS and BCSS in diabetic patients undergoing RC. Given its low cost and demonstrated safety among nondiabetic patients, further studies are warranted to evaluate potential therapeutic and preventive roles of metformin in BC. (C) 2015 Elsevier Inc. All rights reserved.