To be or not to be: The role of serial CA125 monitoring in early endometrial cancer recurrence detection, insights from an ESGO-accredited institution

Objective: Cancer antigen 125 (CA125) has been proposed as a prognostic biomarker in endometrial cancer; however, its role in routine postoperative surveillance remains controversial. This study aimed to evaluate the clinical utility of serial CA125 measurements for detecting endometrial cancer recurrence and to identify a prognostically relevant cutoff value. Methods: We conducted a retrospective observational cohort study of patients with endometrial cancer treated at a single ESGO-accredited institution. Serial CA125 levels were measured at regular intervals during postoperative surveillance. An optimal CA125 cutoff value was derived using receiver operating characteristic analysis based on CA125 levels measured at a predefined 18-month postoperative landmark in patients alive and recurrence-free at that time. Recurrence-free survival was subsequently analyzed using Kaplan–Meier methods. Results: Patients with recurrence showed progressively higher CA125 levels than disease-free patients, with statistically significant differences emerging at 15 months (p-value = 0.014) and 18 months (p-value = 0.005) after surgery. A CA125 cutoff of 9.58 U/mL at 18 months best predicted recurrence. Based on this value, 105 patients were classified as low-risk and 49 as high-risk. ROC curve analysis demonstrated good discriminatory ability (AUC = 0.72, p-value < 0.001). Kaplan–Meier analysis showed significantly worse recurrence-free survival in patients with CA125 ≥ 9.58 U/mL compared to those with lower values (p-value = 0.02). Conclusion: Selective serial monitoring of CA125 during postoperative surveillance may help identify patients at increased risk of endometrial cancer recurrence and serve as an adjunct to imaging and guideline-based risk stratification, pending prospective validation.