Associations of KRAS Point Mutations with Survival of Patients Who Underwent Curative-Intent Resection of Colorectal Liver Metastases.

Background: The oncologic significance of specific KRAS point mutations for patients with colorectal liver metastases (CLM) is uncertain. This study aimed to assess the prognostic impact of KRAS point mutations on patients who underwent surgery for CLM.

Methods: Patients who underwent curative-intent surgery for CLM from 2001 to 2020 were selected for the study. In the study, KRAS point mutations and other clinicopathologic variables were examined for association with survival.

Results: The study classified 798 patients into five groups by KRAS mutation status as follows: wild-type (n = 412, 51.6%), G12D (n = 123, 15.4%), G12V (n = 88, 11.0%), G13D (n = 61, 7.6%), and "Other" mutations (n = 114, 14.3%). For the patients with G12V substitutions, TP53 mutation was associated with worse overall survival (OS) (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.04-6.66; P = 0.041), but was not associated with a survival difference for the other four groups. The patients with co-occurring KRAS G12V and TP53 had a median OS of 4.4 years and a 5-year OS rate of 39.8%. In contrast, the patients with KRAS G12V mutation and wild-type TP53 had a median OS of 7.3 years and a 5-year OS rate of 75.9%, similar to the corresponding values for the patients with wild-type KRAS. Co-occurring KRAS G12V and TP53 mutations were independently associated with worse OS in the entire cohort (HR, 2.08; 95% CI, 1.15-3.76; P = 0.015).

Conclusions: This study showed that KRAS G12V mutation is associated with worse OS for patients undergoing curative-intent CLM resection, but only those with co-occurring TP53 mutation. Prognosis after surgery for CLM should not be stratified by KRAS mutation site alone.