Metformin Use and Kidney Cancer Survival Outcomes: A Systematic Review and Meta-Analysis.

Objectives: Metformin has been associated with improved survival outcomes in various malignancies. However, studies in kidney cancer are conflicting. We performed a systematic review and meta-analysis to evaluate the association between metformin and kidney cancer survival. Materials and Methods: We searched Medline and EMBASE databases from inception to June 2017 to identify studies evaluating the association between metformin use and kidney cancer survival outcomes. We evaluated risk of bias with the Newcastle-Ottawa scale. We pooled hazard ratios (HRs) for recurrence-free, progression-free, cancer-specific, and overall survival using random effects models, and explored heterogeneity with metaregression. We evaluated publication bias through Begg's and Egger's tests, and the trim and fill procedure. Results: We identified 9 studies meeting inclusion criteria, collectively involving 7426 patients. Five studies were at low risk of bias. The direction of association for metformin use was toward benefit for recurrence-free survival (HR, 0.99; 95% confidence interval [ CI], 0.36-2.74), progression-free survival (pooled HR, 0.84; 95% CI, 0.66-1.07), cancer-specific (pooled HR, 0.72; 95% CI, 0.48-1.09), and overall survival (pooled HR, 0.73; 95% CI, 0.50-1.09), though none reached statistical significance. Metaregression found no study-level characteristic to be associated with the effect size, and there was no strong evidence of publication bias for any outcome. Conclusions: There is no evidence of a statistically significant association between metformin use and any survival outcome in kidney cancer. We discuss the potential for bias in chemoprevention studies and provide recommendations to reduce bias in future studies evaluating metformin in kidney cancer.