Conditional Recurrence-Free Survival after Resection of Colorectal Liver Metastases: Persistent Deleterious Association with RAS and TP53 Co-Mutation

BACKGROUND: Conditional recurrence-free survival (RFS) probability, that is, the probability of remaining recurrence-free after a given interval without recurrence, has not been reported after resection of colorectal liver metastases (CLMs). We aimed to estimate conditional RFS and identify factors affecting conditional RFS. STUDY DESIGN: Patients undergoing initial resection of CLMs during 2000-2016 with mutation data were identified. The RFS and risk factors for recurrence were evaluated at the time of resection for all patients and at 1 year and 2 years after resection for patients who remained recurrence-free. RESULTS: Of 2,118 patients, 485 met the inclusion criteria, of which 225 were recurrence-free at 1 year and 109 were recurrence-free at 2 years. The 5-year RFS rates were 17.3%, 36.8%, and 70.7% for all patients and the 1-year and 2-year recurrence-free groups, respectively, when assessed from the time of initial CLM resection. RAS/TP53 co-mutation was the only factor independently associated with increased risk of recurrence for all groups (all patients, hazard ratio 1.47; 95% CI 1.19 to 1.82; p < 0.001; 1-year recurrence-free, hazard ratio 1.69; 95% CI 1.17 to 2.43; p = 0.005; 2-year recurrence-free, hazard ratio 2.41; 95% CI 1.12 to 5.17; p = 0.024). T category, extrahepatic disease, multiple CLMs, largest CLM diameter, and surgical margin status were risk factors for recurrence in all patients and/or the 1-year recurrence-free group, but not the 2-year recurrence-free group. Median RFS was lower for patients with RAS/TP53 co-mutation than for those with RAS/TP53 wild-type in the 1-year (1.5 vs 2.8 years; p = 0.006) and 2-year recurrence-free groups (3.0 vs 5.9 years; p = 0.024). CONCLUSIONS: Conditional RFS is useful for updating prognosis after a given time interval without recurrence after CLM resection. Importantly, RAS/TP53 co-mutation has a persistent deleterious association with recurrence. ((C) 2019 by the American College of Surgeons. Published by Elsevier Inc. All rights reserved.)