Development of a biomarker-guided chemotherapy response model using combined CEA and CA19-9 profiles in esophageal cancer: A real-world pharmacotherapeutic study

Abstract: Background: Esophageal adenocarcinoma is associated with poor survival despite advances in systemic therapy. Readily available serum biomarkers may improve risk stratification; however, their combined role in biomarker-guided treatment decisions remains insufficiently investigated. Objectives: To evaluate the prognostic significance of combined baseline carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels and explore their utility for biomarker-based risk stratification in patients with esophageal adenocarcinoma receiving systemic chemotherapy. Methods: This retrospective real-world cohort study included 38 patients with histologically confirmed esophageal adenocarcinoma who received systemic chemotherapy at a tertiary referral center between January 2016 and December 2021. Patients were classified into three exploratory biomarker-defined risk groups according to baseline serum CEA and CA19-9 levels. Overall survival was evaluated using Kaplan–Meier analysis and Cox proportional hazards regression, while treatment outcomes were explored across biomarker-defined groups and chemotherapy regimens. Results: Elevated baseline CEA and CA19-9 levels were associated with shorter overall survival. Patients with simultaneous elevation of both biomarkers demonstrated the poorest survival outcomes (multivariable hazard ratio = 2.22). Differences in survival were observed across chemotherapy regimen groups within biomarker-defined categories; however, these comparisons were exploratory and may have been influenced by treatment-selection bias and unmeasured clinical factors. Patients with distal or gastroesophageal junction adenocarcinoma showed more favorable outcomes than those with cervical or thoracic tuxzmors. Conclusion: Combined assessment of baseline CEA and CA19-9 may provide a practical and inexpensive approach for biological risk stratification in esophageal adenocarcinoma. However, these findings do not establish that the biomarkers can guide chemotherapy selection. Prospective multicenter studies with independent validation are required to determine their prognostic and predictive value before biomarker-guided treatment selection can be recommended in routine clinical practice.