Prognostic value of CA125, HE4, ROMA, and CPH-I in advanced epithelial ovarian cancer

Optimal cytoreductive surgery and platinum sensitivity are critical prognostic factors in advanced epithelial ovarian cancer (EOC). However, the preoperative value of routinely available serum biomarkers in predicting surgical outcomes, platinum resistance, and disease progression remains unclear.

This retrospective study included patients with benign ovarian tumors (n = 80), early-stage EOC (n = 84), and advanced EOC (n = 97) treated between January 2018 and June 2024. Serum cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) levels were measured before initial treatment, and the Risk of Ovarian Malignancy Algorithm (ROMA) and Copenhagen Index (CPH-I) values were calculated. Predictive performance for surgical outcomes, platinum resistance, and recurrence in advanced EOC was evaluated using receiver operating characteristic analysis, and progression-free survival was analyzed using Kaplan-Meier methods.

Serum CA125, HE4, ROMA, and CPH-I levels progressively increased from the benign ovarian tumor group to the early-stage and advanced-stage EOC groups (P < 0.001). In advanced EOC, significantly higher biomarker levels were observed in patients with suboptimal cytoreduction and disease recurrence (P < 0.05). ROC analysis showed moderate discriminatory ability of all four biomarkers for suboptimal cytoreduction, platinum resistance, and recurrence (P < 0.05). ROMA and CPH-I showed relatively higher AUC values for predicting suboptimal cytoreduction, with AUCs of 0.807 and 0.800, respectively. Kaplan-Meier analysis showed that elevated CA125, HE4, ROMA, and CPH-I levels were significantly associated with shorter progression-free survival (P < 0.005). Multivariable Cox regression analyses further demonstrated that CA125, HE4, ROMA, and CPH-I remained independently associated with unfavorable progression-free survival after adjustment for clinicopathological confounders.

Elevated serum CA125, HE4, ROMA, and CPH-I are associated with unfavorable surgical outcomes, platinum resistance, and poor prognosis in advanced EOC. ROMA and CPH-I, in particular, may serve as valuable adjunctive tools for preoperative prediction of cytoreductive surgery outcomes, while all four biomarkers contribute to risk stratification for platinum sensitivity and disease progression. These findings support the potential role of combined serum biomarker assessment in guiding individualized treatment strategies for patients with advanced EOC.