The Impact of Metformin Use with Survival Outcomes in Urologic Cancers: A Systematic Review and Meta-Analysis

Abstract

Background. Conflicting results exist between the potential protective effects of metformin and the prognosis of urologic cancers. This meta-analysis summarized the effects of metformin exposure on the recurrence, progression, cancer-specific survival (CSS), and overall survival (OS) of the three main urologic cancers (kidney cancer, bladder cancer, and prostate cancer). Methods. We systematically searched PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases (January 2010 to December 2019), which identified studies regarding metformin users and nonusers with urologic cancers and extracted patient data. A random effect model or fixed effect model was used to analyze hazard ratios (HRs) and 95% confidence intervals (CIs). Results. Among the 1883 confirmed studies, 27 eligible studies were identified, including 123,212 participants. In prostate cancer, patients using metformin have significant benefits for recurrence ( $\text{HR}=0.74$ ; 95% CI: 0.61-0.90; $P=0.007$ ; $I^2=56\%$ ), CSS ( $\text{HR}=0.74$ ; 95% CI: 0.61-0.91; $P=0.002$ ; $I^2=79\%$ ), and OS ( $\text{HR}=0.76$ ; 95% CI: 0.65-0.90; $P<0.001$ ; $I^2=86\%$ ). Moreover, further subgroup analysis showed that the beneficial effects of metformin may be more significant for patients receiving radical radiotherapy. For kidney cancer, metformin was beneficial for progression ( $\text{HR}=0.80$ ; 95% CI: 0.65-0.98; $P=0.14$ ; $I^2=46\%$ ). Analysis revealed that the effect of metformin on the overall survival of kidney cancer patients may be related to nationality (American: $\text{HR}=0.76$ ; 95% CI: 0.59-0.98; $P=0.88$ ; $I^2=0\%$ ). For bladder cancer, no obvious benefits of metformin use were identified. However, subgroup analysis indicated that metformin may improve the recurrence of bladder cancer, but this improvement was only found in patients with a median follow-up time of more than 4 years ( $\text{HR}=0.43$ ; 95% CI: 0.28-0.67; $P=0.61$ ; $I^2=0\%$ ).