Carcinoembryonic Antigen Levels and Survival in Stage III Colon Cancer: Post hoc Analysis of the MOSAIC and PETACC-8 Trials

Background: We explored and validated the association of postoperative carcinoembryonic antigen (CEA) with disease-free survival (DFS) and overall survival (OS) in stage III colon cancer. Methods: Patients with stage III colon cancer from the MOSAIC and PETACC-8 trials were enrolled. The relation between CEA and outcomes was continuously modeled with the restricted cubic splines (RCS) method. Association of CEA with outcomes was assessed by the Kaplan–Meier method, with two risk groups among patients with a CEA level ≤5 ng/mL. Multivariate Cox proportional hazard models were constructed. Results: The CEA level was available in 1,292 (96%) and 2,477 (97%) patients in the discovery and validation cohorts. The RCS analysis confirmed that patients with a CEA level >5 ng/mL were at highest risk of recurrence or death and those with a CEA level ≤5 ng/mL presented a heterogeneous risk population. In the discovery cohort, the 3-year DFS rate was 75%, 65%, and 45% in a group of patients with CEA level of 0–1.30 ng/mL (n = 630), 1.30–5 ng/mL (n = 613), and >5 ng/mL (n = 49), respectively (P < 0.001). CEA was independently associated with endpoints. All findings were confirmed in the validation cohort. Conclusions: Postoperative CEA level was highly and independently associated with DFS and OS, especially in patients with a CEA level of ≤5 ng/mL, suggesting that this cutoff is not optimal. Impact: CEA levels should be applied more accurately in future trials and clinical practice.