RAS/TP53 co-Mutation is Associated with Worse Survival after Concurrent Resection of Colorectal Liver Metastases and Extrahepatic Disease

ObjectiveTo determine if tumor genetics are associated with overall survival (OS) after concurrent resection of colorectal liver metastases (CLM) and extrahepatic disease (EHD).Summary background dataThe prognosis for patients who undergo concurrent resection of CLM/EHD is unclear and the impact of somatic mutations has not been reported.MethodsPatients undergoing concurrent resection of CLM and EHD from 2007-2017 were identified from two academic centers. From 1 center, patients were selected from a pre-existing database of patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). The Kaplan-Meier method was used to construct survival curves, compared using the log-rank test. Multivariable Cox analysis for OS was performed.ResultsOne hundred nine patients were included. Most common EHD sites included lung (33 patients), peritoneum (32), and portal lymph nodes (14). TP53 mutation was the most common mutation, identified in 75 patients (69%), and RAS/TP53 co-mutation was identified in 31 patients (28%). The median OS was 49 months (IQR, 24-125), and 3- and 5-year OS rates were 66% and 44%, respectively. Compared to patients without RAS/TP53 co-mutation, patients with RAS/TP53 co-mutation had lower median OS: 39 vs. 51 months (P = .02). On multivariable analysis, lung EHD (hazard ratio [HR], 0.7; 95% CI, 0.3-1.4), peritoneal EHD (HR, 2.2; 95% CI, 1.1-4.2) and RAS/TP53 co-mutation (HR, 2.8; 95% CI, 1.1-7.2) were independently associated with OS.ConclusionsRAS/TP53 co-mutation is associated with worse OS after concurrent CLM/EHD resection. Mutational status and site of EHD should be included in the evaluation of patients considered for concurrent resection.