Clinical impact of KRAS mutation status on recurrence patterns and the efficacy of local therapy after hepatectomy for colorectal liver metastases

Background Kirsten rat sarcoma viral oncogene homolog ( KRAS ) is one of the most frequently mutated oncogenes in colorectal cancer. We aimed to clarify the clinical impact of KRAS mutation status on recurrence patterns, surgical management of recurrent lesions, and prognostic outcomes after curative hepatectomy for colorectal liver metastases (CRLM). Methods This retrospective study included 190 CRLM patients who underwent curative (macroscopic R0 resection) hepatectomy and had known KRAS status (wild-type [WT]: 62.1%; mutant [MT]: 37.9%). Results KRAS mutations were identified in 72 patients. Compared to the WT group, the MT group exhibited significantly shorter overall survival (OS) and recurrence-free survival (RFS). The MT group was characterized by more frequent early recurrence (within 1 year), multiple lesions, and multi-organ metastases. Multivariate analysis identified KRAS mutation as an independent predictor of poor OS and RFS, whereas CEA ≥ 5 ng/mL was independently associated with OS but not RFS. Notably, among patients who experienced recurrence, those who underwent local therapy (repeat resection or ablation) showed comparable OS between the MT and WT groups. Conversely, in patients who did not receive local therapy, the MT group had significantly worse OS. Mutation sites (G12, G13, others) did not significantly influence outcomes. Conclusions: KRAS mutations are associated with aggressive recurrence patterns and a poor prognosis in CRLM. However, active local therapy for recurrent lesions may mitigate this adverse impact, achieving survival outcomes comparable to those of WT cases.