Preoperative serum HE4 combined with CA125 testing for predicting the risk of suboptimal cytoreduction in advanced epithelial ovarian cancer.

OBJECTIVE: To investigate the predictive value of preoperative serum markers centered on human epididymis protein 4 (HE4) combined with carbohydrate antigen 125 (CA125) for the risk of suboptimal cytoreduction in advanced epithelial ovarian cancer. METHODS: We retrospectively analyzed the clinical data of 102 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIA-IV epithelial ovarian cancer who underwent primary cytoreductive surgery at the First People's Hospital of Jiangxia District between January 2021 and December 2025. Patients were divided into an optimal cytoreduction group (n=65) and a suboptimal cytoreduction group (n=37) based on the size of postoperative residual lesions. Preoperative HE4 and CA125 levels were compared between the two groups. Restricted cubic spline (RCS) functions were used to analyze dose-response relationships. Multivariate Logistic regression was applied to screen independent risk factors and construct a combined prediction model. Model performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Preoperative HE4, CA125, and platelet counts were significantly higher in the suboptimal cytoreduction group than in the optimal cytoreduction group (all P<0.001). RCS analysis showed a linear positive correlation between marker levels and the risk of suboptimal cytoreduction. Multivariate regression revealed that each 50 pmol/L increase in HE4 (odds ratio [OR]=1.25), each 100 U/mL increase in CA125 (OR = 1.68), and each 10×109/L increase in platelets (OR = 1.27) were independent risk factors (all P<0.05). The combined model achieved an area under the ROC curve (AUC) of 0.959 for predicting suboptimal cytoreduction, with a sensitivity of 81.1%, specificity of 95.4%, and accuracy of 90.2%, significantly outperforming single markers. Calibration curves showed good model fit (P = 0.431), and DCA demonstrated significant net clinical benefit at threshold probabilities ranging from 0.1 to 0.9. CONCLUSION: Combined preoperative detection of serum HE4, CA125, and platelet count shows preliminary predictive potential for the risk of suboptimal cytoreduction in advanced epithelial ovarian cancer. In this single-center retrospective cohort, the three-marker combined model demonstrated promising internal predictive performance; however, its clinical applicability remains preliminary and center-specific, pending validation in independent external cohorts.