Initial serum CA-125 and HE4 levels as predictors for optimal surgical cytoreduction in patients with stage III epithelial ovarian cancer

Abstract Background: Ovarian cancer (OC) lacks specific symptoms and screening methods, and most patients are diagnosed at an advanced stage with worse prognosis. Currently, the major treatment approaches for advanced epithelial ovarian carcinoma (AEOC) have been primary debulking surgery (PDS) followed by platinum-based chemotherapy, and neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). Serum CA125 has been widely used as an indicator for OC diagnosis and management. It is generally believed that preoperative serum CA125 level is associated with tumor burden, and some studies have attempted to evaluate its level to obtain optimal resection rate. HE4 is also a promising biomarker for OC. The aim of the study is to explore whether serum CA125 and HE4 levels in stage III epithelial ovarian cancer predict optimal surgical cytoreductive outcomes. Methods: The clinical data of 201 stage III ovarian cancer patients, diagnosed at our institution from January 2013 to June 2019, were retrospectively collected. According to the initial treatment modality, patients were divided into groups: NACT followed by IDS (89 women) group and by PDS (112 women) group. Differences in patient characteristics were compared using the chi-square test and t-test, and disease-free survival (DFS) was calculated using the Kaplan-Meier method. ROC analysis was used to determine the cut-off values of serum CA-125 and HE4. Results: The medium initial serum levels of CA125 (1359.6 IU/ml vs.759.5 IU/ml, p ˂ 0.001) and HE4 (661 pmol/L vs. 244 pmol/L, p ˂ 0.001) were significantly higher in the NACT group compared with those in the PDS group. Serum CA125 and HE4 levels after NACT decreased by 96.30% and 96.23%, respectively. If the preoperative serum CA-125 value was 500 IU/ml, the probability of achieving R0 was 63.9%. When the preoperative serum HE4 value was 250pmol/L, there was a 65.80% chance of obtaining complete gross cytoreduction. The median DFS was 20 months and 20.5 months in the NACT and PDS groups, respectively. No significant difference in DFS was observed between the two groups (p = 0.851). Conclusion: The efficacy of NACT combined with IDS treatment and PDS for advanced ovarian cancer are comparable. Initial serum CA125 and HE4 levels of 500IU/ml and 250 pmol/L are appropriate cut-off values for predicting the absence of gross residual lesions. CA125 and HE4 values can serve as predictors of optimal surgical cytoreduction. Nevertheless, more clinical studies are needed for further validation.