Multicenter study of ovarian cancer score for diagnosing ovarian cancer.

Background: Early detection is crucial for improving survival of patients with ovarian cancer (OC), yet current diagnostic tools lack adequate sensitivity and specificity, especially for early stage disease. The study aimed to validate the serum small extracellular vesicles (sEV) protein based Ovarian Cancer Score (OCS) in detecting OC.

Methods: This multicenter study included 1183 adult females with adnexal masses from four hospitals in China (October 2019-April 2023). Of these, 1024 samples were prospectively collected, and 159 were from biobanks. All serum samples were collected before surgery. The concentrations of sEV carbohydrate antigen 125 (CA125), human epididymis protein 4 (HE4), and complement component 5a protein (C5a) were quantified using chemiluminescence immunoassay and then used for calculating OCS. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated.

Results: The OCS demonstrated high sensitivity (95.4 %) and specificity (90.4 %) in diagnosis of OC in the prospective cohort (n = 1024) and in total cases (n = 1183, 95.5 % and 90.2 %), with stable performance across menopausal status and FIGO stages. The OCS maintained a high specificity in premenopausal patients (89.6 %) and postmenopausal patients (92.1 %). The OCS showed high sensitivity in early stage epithelial OC (FIGO I: 89.7 %, I + II: 91.4 %), in patients aged ≤45 years (92.7 %), and in patients with normal CA125 levels (72.7 %), although these results were obtained from subgroups with small sample sizes.

Conclusion: This multicenter study demonstrated that the OCS is a promising non-invasive diagnostic tool for the detection of OC.

Trial Registry: This study was registered at ClinicalTrials.gov: NCT06366997.