Metformin: A Promising Radiosensitizer in Neoadjuvant Rectal Cancer Treatment

Background: Neoadjuvant chemoradiotherapy (nCRT) decreases the risk of local recurrence after surgery in patients with locally advanced rectal cancer (LARC) and metformin is constantly gaining scientific interest due to its potentially radiosensitizing effect. Objective: This review article aims to better clarify the role of metformin as a radiosensitizer in patients with LARC undergoing neoadjuvant concurrent chemoradiotherapy. Methods: We used the PubMed database to retrieve journal articles and the inclusion criteria were all human studies that illustrated the effective role of metformin in the neoadjuvant setting of locally advanced rectal cancer. Results: Our search resulted in 17 citations, of which 10 eventually fulfilled the inclusion criteria of our study. Promising results (improved tumor and nodal regression as well as higher pathologic complete response rate) have been occasionally documented with metformin use in some of the included studies. However, regarding survival and all-cause mortality, no significant difference has been found. Conclusion: Metformin might constitute a highly promising radiosensitizer in neoadjuvant LARC treatment attracting much scientific interest. Due to the lack of studies with high evidence, further advanced research is required to enhance the existing knowledge about its potential value in this field.