Is Metformin Associated With Improved Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

ABSTRACT Efforts to determine whether metformin can increase the effectiveness of neoadjuvant chemoradiotherapy in rectal cancer have increased in recent years. However, retrospective studies have yielded inconclusive results. Objectives The aim of this study was to compare oncological outcomes and survival after neoadjuvant chemoradiotherapy in patients with rectal cancer taking metformin versus in those not taking metformin. Methods This study analyzed 423 consecutive patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy and curative surgery between January 2010 and May 2020; of these, 59 were taking metformin and 364 were not taking metformin. Results Patients taking metformin had a lower proportion of tumor regression (6.8% versus 22.0%, P = 0.012) as well as a lower proportion of patients achieving a pathological complete response (6.8% versus 20.6%, P = 0.011). In the multivariate analysis, independent predictors of pathologic complete response were not taking metformin (OR: 5.26, 95% CI: 1.12-24.85, P= 0.035) and cT2 stage (OR: 3.49, 95% CI: 1.10-11.07, P= 0.034); the interval was also an independent predictor of tumor regression (OR: 1.78, 95% CI: 1.06-2.96, P= 0.028). No differences were observed in survival between groups. Conclusion Metformin was not associated with better tumor responses or survival after neoadjuvant treatment.