Prognostic role of KRAS mutational status and response to preoperative chemotherapy in patients undergoing hepatectomy for colorectal liver metastases

Abstract

Background: Both pattern of response to preoperative chemotherapy (pCHT) and KRAS mutational status are associated with survival following hepatectomy for colorectal liver metastases (CLM). The current study aims at investigating the prognostic role of these two factors in a large cohort of patients from a single high volume hospital. Methods: Data on 281 patients with a known KRAS mutation status who underwent curative resection for CLM after pCHT were reviewed. Recurrence-free (RFS) and disease-specific survival (DSS) were compared according to KRAS mutational status (mutated (mutKRAS) vs wild-type (wtKRAS)) and to response to pCHT (progression/stability (PD/SD) vs partial/complete response (PR/CR)). Results: At univariate analysis, mtKRAS and PD/SD after pCHT were associated with significantly shorter RFS (p=.015 and p=.024, respectively) and DSS (p=.026 and p=.006, respectively) and independently predicted an higher risk of recurrence (Hazard-Ratio(HR)=1.6 and 1.4,respectively) and mortality (HR=2.1 and 1.6,respectively). Subgroup analysis showed that, among patients with PD/SD after pCHT, mtKRAS was still associated with poorer outcomes both at the univariate and multivariate analysis (all p<.05), compared to wtKRAS. Conclusion: mtKRAS and lack of response to pCHT are both independently associated with poor survival outcomes after CLM resection. KRAS mutational status may further stratify survival among patients not responding to pCHT.