Is hepatectomy justified for patients with RAS mutant colorectal liver metastases? An analysis of 524 patients undergoing curative liver resection

Background. RAS mutations are associated with limited overall survival after resection of colorectal liver metastases. Our aim was to determine criteria for considering hepatectomy for patients with RAS mutant colorectal liver metastases. Methods. Of 1,163 patients who underwent liver resection for colorectal liver metastases during 20052014, all patients operated on with curative intent who had known RAS mutation status were included. Factors associated with overall survival were determined using multivariate analysis. Results. A total of 524 patients met the inclusion criteria; 212 (40 %) had mutated RAS. Mutations were located on codon 12 in 128 patients (60%) and codon 13 in 29 (14 %). At median follow-up of 38 months, median overall survival was 72.6 months for wild-type RAS and 50.9 months for mutated RAS (P < .001). Median overall survival for patients with codon 12 and 13 mutations was 51.9 and 50.9 months, respectively (P =.839), significantly worse than for patients with wild-type RAS (P =.005, and P =.038 for codon 12 and 13, respectively). For patients with RAS mutation, factors associated independently with worse overall survival were node-positive primary tumor, tumor > 3 cm, and > 7 cycles of preoperative chemotherapy. Major and 2-stage hepatectomy were not associated independently with overall survival. Median overall survival was 57, 41, and 21.5 months for patients with 1, 2, and 3 risk factors, respectively. There were no 4-year survivors in the highest-risk group. Conclusion. Patients with multiple risk factors had poor overall survival after curative resection of RAS mutant colorectal liver metastases. For such patients, hepatectomy may be ill advised, and alternative therapies or further systemic therapy should be considered.