Beyond Carcinoembryonic Antigens: The Role of CA-125 and CA-199 in Predicting Prognosis of Lung Adenocarcinoma

Abstract

Background: Lung adenocarcinoma in Taiwan has unique characteristics, such as a high EGFR mutation rate. While CEAs are a commonly used serum tumor marker (STM), the prognostic value of CA-125, CA-153, and CA-199 remains unclear. This study evaluates their clinical utility in predicting disease progression and prognosis. Methods: A multicenter retrospective study of 1133 patients with lung adenocarcinoma from three hospitals in Taiwan was conducted (2014-2021). Clinical data and STM levels (CEA, CA-125, CA-153, CA-199) were collected. Cox proportional hazards models were used to identify independent predictors of disease-free survival (DFS) and progression-free survival (PFS). Results: CEA, CA-125, CA-153, and CA-199 levels increased with lung adenocarcinoma stage (p < 0.001). In the early stages, CEA was an independent predictor of DFS (HR = 2.58, p < 0.001). In stage IV patients, CA-125 and CA-199 predicted poor PFS (CA-125: HR = 1.17, p = 0.004; CA-199: HR = 1.09, p = 0.049). Among those treated with EGFR tyrosine kinase inhibitors (TKIs), CA-125 remained a significant predictor (HR = 1.33, p < 0.001). Conclusions: CA-125 and CA-199 may be superior to CEAs in predicting poor PFS in stage IV lung adenocarcinoma, especially for EGFR TKI-treated patients. These easily accessible markers could aid prognosis and treatment decisions, although further validation is required.