Association ofRASMutation Location and Oncologic Outcomes After Resection of Colorectal Liver Metastases

Background RASmutations are prognostic for patients with metastatic colorectal cancer (mCRC). We investigated clinical, pathologic, and survival differences based onRASexon for patients with colorectal liver metastases (CRLM). Methods This retrospective, single-center study included patients with R0/R1 resection of CRLM from 1992 to 2016. Patients with unresected extrahepatic disease or liver-first resection were excluded. Overall survival (OS) and recurrence-free survival were assessed and stratified by mutation status and location. Fisher's exact test, Wilcoxon rank-sum test, and log-rank test were used, where appropriate. Results A total of 938 mCRC patients were identified with median age of 57 (range 19-91). Of the 445 patients withKRASmutations, 407 (91%) had a mutation in exon 2, 14 (3%) exon 3, and 24 (5%) exon 4. Median OS was 71.4 months (95% confidence interval [CI] 66.1-76.5). Patients withKRASmutations had worse OS compared withKRASwild-type patients (median 55.5 vs. 91.3 months,p < 0.001). While there was no significant difference in OS based on the exon mutated (p = 0.12), 5-year OS was higher for patients with exon 4 mutations [68.8% (95% CI 0.45-0.84)] compared with those with mutations in exon 2 [45.7% (95% CI 0.40-0.51)] or exon 3 [39.1% (95% CI: 0.11-0.68)]. Patients withNRASmutant tumors also had worse OS compared withNRASwild-type patients (median 50.9 vs. 73.3 months,p = 0.03). Conclusions NRASandKRASexon 3/4 mutations are present in a minority of mCRC patients. Patients with exon 4 mutant tumors may have a more favorable prognosis, although the difference in oncologic outcomes based on mutated exon appears to be smaller than previously reported.