Anatomical Resections Improve Disease-free Survival in Patients With KRAS-mutated Colorectal Liver Metastases

Objective: To investigate the potential clinical advantage of anatomical resection versus nonanatomical resection for colorectal liver metastases, according to KRAS mutational status. Background: KRAS-mutated colorectal liver metastases ( CRLM) are known to be more aggressive than KRAS wild-type tumors. Although nonanatomical liver resections have been demonstrated as a viable approach for CRLM patients with similar oncologic outcomes to anatomical resections, this may not be the case for the subset of KRAS-mutated CRLM. Methods: 389 patients who underwent hepatic resection of CRLM with known KRAS mutational status were identified. Survival estimates were calculated using the Kaplan-Meier method, and multivariable analysis was conducted using the Cox proportional hazards regression model. Results: In this study, 165 patients (42.4%) underwent nonanatomical resections and 140 (36.0%) presented with KRAS-mutated CRLM. Median disease-free survival (DFS) in the entire cohort was 21.3 months, whereas 1-, 3-, and 5-year DFS was 67.3%, 34.9%, and 31.5% respectively. Although there was no difference in DFS between anatomical and nonanatomical resections in patients with KRAS wild-type tumors (P - 0.142), a significant difference in favor of anatomical resection was observed in patients with a KRAS mutation (10.5 vs. 33.8 months; P < 0.001). Five-year DFS was only 14.4% in the nonanatomically resected group, versus 46.4% in the anatomically resected group. This observation persisted in multivariable analysis (hazard ratio: 0.45; 95% confidence interval: 0.27-0.74; P - 0.002), when corrected for number of tumors, bilobar disease, and intraoperative ablations. Conclusions: Nonanatomical tissue-sparing hepatectomies are associated with worse DFS in patients with KRAS-mutated tumors. Because of the aggressive nature of KRAS- mutated CRLM, more extensive anatomical hepatectomies may be warranted.