CEA Rebound After Discontinuation of Pre-Hepatectomy Chemotherapy Predicts Worse Outcomes After Resection of Colorectal Cancer Liver Metastases

Background. Carcinoembryonic antigen (CEA) levels may vary with administration and discontinuation of pre-hepatectomy chemotherapy in patients undergoing resection of colorectal cancer liver metastases (CLM). The prognostic significance of these changes, termed CEA dynamics, is unclear. Patients and Methods. Consecutive patients undergoing hepatectomy for CLM (2001-2021) at a comprehensive cancer center were included. CEA dynamics were classified as CEA normal (CEA < 5 ng/mL before, during, and after chemotherapy), CEA decrease (elevated CEA levels that drop during and after chemotherapy), and CEA rebound (elevated CEA levels that drop during chemotherapy but rebound upon discontinuation). Recurrence-free (RFS), hepatic-specific disease-free (hDFS), and overall survival (OS) were compared across CEA dynamics groups. Results. Of 903 patients, 254 (28%) were CEA normal, 423 (47%) were CEA decrease, and 226 (25%) were CEA rebound. Median RFS was 15.9 months, median hDFS was not reached, and median OS was 11.9 years for CEA normal patients. By comparison, CEA decrease and CEA rebound patients had shorter median RFS (12.2 months, P = 0.002 and 7.4 months, P < 0.001, respectively), shorter median hDFS (29.1 months, P = 0.003 and 14.8 months, P < 0.001, respectively), and shorter median OS (7.1 years, P = 0.131, and 4.9 years, P < 0.001, respectively). On multivariable analysis, CEA rebound was an independent predictor of worse RFS [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.16-1.93], hDFS (HR 1.39, 95% CI 1.03-1.88), and OS (HR 1.79, 95% CI 1.18-2.73). Among patients with CEA rebound, RAS-BRAF/TP53 comutation and multiple tumors predicted worse OS while APC mutation predicted improved OS. Conclusion. CEA rebound between pre-hepatectomy chemotherapy discontinuation and CLM resection is associated with worse oncologic outcomes, particularly in patients with aggressive tumor biology, and may help frame patient and surgeon expectations ahead of CLM resection.