Improved Survival over Time After Resection of Colorectal Liver Metastases and Clinical Impact of Multigene Alteration Testing in Patients with Metastatic Colorectal Cancer

Background: The past 20 years have seen advances in colorectal cancer management. We sought to determine whether survival in patients undergoing resection of colorectal liver metastases (CLM) has improved in association with three landmark advances: introduction of irinotecan- and/or oxaliplatin-containing regimens, molecular targeted therapy, and multigene alteration testing. Methods: Patients undergoing CLM resection during 1998–2014 were identified and grouped by resection year. The influence of alterations in RAS, TP53, and SMAD4 was evaluated and validated in an external cohort including patients with unresectable metastatic colorectal cancer. Results: Of 1961 patients, 1599 met the inclusion criteria. Irinotecan- and/or oxaliplatin-containing regimens and molecular targeted therapy were used for more than 50% of patients starting in 2001 and starting in 2006, respectively, so patients were grouped as undergoing resection during 1998–2000, 2001–2005, or 2006–2014. Liver resectability indications expanded over time. The 5-year overall survival (OS) rate was significantly better in 2006–2014, vs. 2001–2005 (56.5% vs. 44.1%, P < 0.001). RAS alteration was associated with worse 5-year OS than RAS wild-type (44.8% vs. 63.3%, P < 0.001). However, OS did not differ significantly between patients with RAS alteration and wild-type TP53 and SMAD4 and patients with RAS wild-type in our cohort (P = 0.899) or the external cohort (P = 0.932). Of 312 patients with genetic sequencing data, 178 (57.1%) had clinically actionable alterations. Conclusion: OS after CLM resection has improved with advances in medical therapy and surgical technique. Multigene alteration testing is useful for prognostication and identification of potential therapeutic targets.