Reevaluating The Prognostic Value Of Ras Mutation Status In Patients With Resected Liver Metastases From Colorectal Cancer: A Systematic Review And Meta-Analysis

Background Although the value of Rat Sarcoma Oncogene (RAS) mutation status in predicting long-term outcomes in patients with colorectal liver metastases (CRLM) is widely accepted, the magnitude of its impact has recently been challenged by three large cohort studies. The aim of this meta-analysis is to reevaluate the impact of RAS mutations on overall survival (OS) and disease-free survival (DFS) in patients who underwent curative-intent resection of CRLM. Methods A comprehensive literature search was performed for studies reporting outcomes of patients undergoing curative-intent surgery stratified by RAS mutation status. Exclusion criteria were defined a priori. Subgroup analysis was performed to evaluate the effect of publication date, sample size, and KRAS vs any RAS mutation on overall outcomes. Results Ten studies incorporating 3115 patients with known RAS status were identified. Pooled results revealed significantly worse OS (Hazard Ratio 1.5, 95% CI 1.31-1.71) and DFS (Hazard Ratio 1.36, 95% CI 1.22-1.52) in RAS-mutated patients. Subgroup analyses revealed that studies including more than 300 patients or published after 2015 reported lower HR than their counterparts. Conclusion The results of this meta-analysis suggest that the prognostic value of RAS mutation status in patients with CRLM has been previously overestimated.