KRAS G12V mutation is associated with worse disease-free survival in patients with stage II colorectal cancer: a single-center retrospective study

KRAS mutations are common in colorectal cancer (CRC), but the prognostic significance of individual variants in stage II disease remains uncertain. We evaluated the associations of KRAS mutation subtypes, particularly G12V, with disease-free survival (DFS) and explored whether G12V modified the association between adjuvant chemotherapy (ACT) and DFS. This single-center retrospective cohort included patients with stage II CRC who underwent curative-intent surgery between May 2011 and March 2021 and had documented KRAS mutation status and available clinicopathological and follow-up data. Patients with BRAF -mutated or dMMR/MSI-H tumors were excluded from the primary survival analysis. DFS was evaluated using the Kaplan-Meier method and Cox regression, and a G12V-by-ACT interaction was assessed in an exploratory analysis. Among 807 patients included in the primary analysis, 322 (39.9%) had KRAS -mutant tumors, including 71 (22.0%) with G12V. Patients with KRAS -mutant tumors had shorter DFS than those with KRAS / BRAF wild-type tumors (HR = 1.53, 95% CI 1.00-2.33, p = 0.048). Patients with G12V-mutated tumors had shorter DFS than those with KRAS/BRAF wild-type tumors (HR = 1.98, 95% CI 1.04-3.75, p = 0.036). In multivariable analysis, G12V remained significantly associated with shorter DFS (HR = 2.13, 95% CI 1.10-4.15, p = 0.026). The G12V-by-ACT interaction was not statistically significant (interaction HR = 2.09, 95% CI 0.55–7.92, p for interaction = 0.275). KRAS G12V remained significantly associated with shorter DFS after adjustment for established clinicopathological factors, supporting its potential role as an adverse prognostic factor in stage II CRC. However, its value in predicting ACT benefit was not demonstrated. Larger multicenter studies with longer follow-up are needed to validate its prognostic significance and potential clinical utility. Not applicable.