External validation of CEA and CA125 prediction model for lymph node metastasis in endometrial cancer: A multi-institute cohort study

Background We previously utilized pretreatment tumor markers Carcinoembryonic Antigen (CEA) and Cancer Antigen 125 (CA125) for predicting lymph node metastasis (LNM) in endometrioid endometrial cancer (EC). Objective The aim of this study was to externally validate a nomogram developed in our previous single-center retrospective study. Methods A multi-center validation study was conducted to recruit endometrioid EC patients from four branches of Chang Gung Memorial Hospital between 2009 and 2021, with patients participating in the original research being excluded. The previously established nomogram was applied with optimal cut-off values for CEA 1.4 ng/ml and CA125 40 U/mL identified through receiver operating characteristic (ROC) curves. The concordance index (C-index) was calculated to assess discrimination, and comparative negative predictive value (NPV) and negative likelihood ratio (NLR) were determined. Decision curve analysis (DCA) was plotted to evaluate our predictive model's clinical utility and net benefit. Results Overall, 1271 patients were included in this external validation study. The results demonstrated a C-index of 0.727, indicating moderate discrimination ability of the nomogram in predicting LNM in this independent cohort. Comparative analysis of NPV 97.2% and NLR 0.36 revealed performance metrics consistent with the original study, reinforcing the nomogram's potential clinical utility in ruling out the possibility of LNM if both pretreatment CEA and CA125 were less than 1.4 ng/ml and 40 U/mL, respectively. The DCA indicated that the nomogram provided clinical utility. Conclusion The reproducible performance metrics in the independent large sample cohort underscore the robustness and generalizability of utilizing CEA and CA125 as predictors of LNM in endometrioid EC, suggesting its potential as a simple tool for clinicians in preoperative decision-making regarding lymphadenectomy.