Journal Article

A novel risk classification model integrating CEA, ctDNA, and pTN stage for stage 3 colon cancer: a post hoc analysis of the IDEA-France trial

Samaille, Thomas, Falcoz, Antoine, Taieb, Julien, Auclin, Edouard, André, Thierry, Laurent-Puig, Pierre, Vernerey, Dewi, Cohen, Romain

2024

Overview

Background We assessed the added value of incorporating carcinoembryonic antigen (CEA) to circulating tumor DNA (ctDNA) and pathological TN (pTN) stage for risk classification in stage 3 colon cancer (CC). Patients and Methods We retrospectively analyzed postoperative CEA values in patients with CC from the IDEA-France phase 3 trial. The relation between disease-free survival (DFS) and CEA was modeled through restricted cubic splines. Prognostic value of CEA, ctDNA, and pTN was assessed with the Kaplan-Meier method. Multivariate analysis was used to identify prognostic and predictive factors for DFS. Results Among 696 patients (35%), CEA values were retrievable, and for 405 (20%) both CEA and ctDNA were available. An optimized CEA threshold of 2 ng/mL was identified, the 3-year DFS was 66.4% for patients above the threshold and 80.9% for those below (HR, 1.74; 95% CI, 1.33-2.28, P < .001). In multivariate analysis, CEA ≥ 2 ng/mL contributed significantly to model variability, becoming an independent prognostic factor for DFS (HR, 1.82; 95% CI,1.27-2.59), alongside ctDNA (HR, 1.88; 95% CI, 1.16-3.03) and pTN (HR, 1.78; 95% CI, 1.24-2.54). A novel integrated risk classification combining CEA, ctDNA, and pTN stage reclassified 19.8% of pT4/N2 patients as low risk and 2.5% of pT3/N1 patients as high risk. This new classification demonstrated the 3-year DFS of 80.8% for low-risk patients and 55.4% for high-risk patients (HR, 2.66, 95% CI, 1.84-3.86, P < .001). Conclusions Postoperative CEA value is a prognostic factor for DFS in stage 3 CC, independently of ctDNA and pTN. It advocates for systematic reporting in future adjuvant trials. Integrating both biomarkers with pTN could refine risk classification in stage 3 CC. This study assessed the added value of incorporating carcinoembryonic antigen to circulating tumor DNA and pathological TN stage for risk classification in stage 3 colon cancer.

• Publisher: Oxford University Press
• Subject: Adult / Aged / Biomarkers, Tumor - blood / Biomarkers, Tumor - genetics / Carcinoembryonic Antigen - blood / CEA (Oncology) / Circulating Tumor DNA - blood / Circulating Tumor DNA - genetics / Classification / Colon cancer / Colonic Neoplasms - blood / Colonic Neoplasms - genetics / Colonic Neoplasms - mortality / Colonic Neoplasms - pathology / Colonic Neoplasms - surgery / Colorectal cancer / Disease-Free Survival / Drug therapy / Extrachromosomal DNA / Female / Growth factors / Health aspects / Humans / Male / Measurement / Methods / Middle Aged / Multivariate analysis / Neoplasm Staging / Prognosis / Retrospective Studies / Risk Assessment - methods / Tumor staging