Validation of the performance of Ovarian Cancer Score for diagnosing ovarian cancer in a multicenter study.

5550 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 Ovarian Cancer Score (OCS) is a newly developed serum extracellular based diagnosis marker for detection of ovarian cancer. The study aimed to explore the performance of 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, 1,024 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. CA125, HE4, and ROMA index results were retrieved from the medical record system at each hospital. The differences was calculated using. Results: The OCS demonstrated high sensitivity (95.5%, 95%CI: 93.3%-97.7%) and specificity (90.2%, 95%CI: 88.2%-92.2%) in OC in the cohort (n = 1183), significantly outperforming CA125 (90.0%, 95%CI: 86.8%-93.3% and 69.1%, 95%CI: 65.9%-72.2%) and ROMA (89.2%, 95%CI: 83.2%-95.2% and 83.1%, 95%CI: 79.3%-86.8%, all p<0.05). OCS was superior to HE4 in sensitivity (75%, 95%CI: 70.1%-79.9%, p<0.001), but not specificity (94.8%, 95%CI: 93.2%-96.5%, p<0.001). Subgroup analysis revealed that in premenopausal women, OCS showed higher sensitivity (94.3%, 95%CI: 90.2%-98.4%) compared to HE4 (79.0%, 95%CI: 71.5%-86.4%, p<0.001) and ROMA (83.0%, 95%CI: 72.2%-93.7%, p<0.05). The specificity of OCS was higher than CA125 and ROMA, but lower than HE4 (all p<0.05). In postmenopausal women, OCS showed higher sensitivity (96.2%, 95%CI: 93.6%-98.8%) than CA125 (89.9%, 95%CI: 85.8%-94.0%, p<0.05) and HE4 (72.6%, 95%CI: 66.2%-79.0%, p<0.001), but there was no significant difference in sensitivity between OCS and CA125 or ROMA (p>0.05). In early-stage OC (FIGO I+II), OCS’s sensitivity (91.4%, 95%CI: 86.8%-96.1%) was significant higher than CA125 (78.4%, 95%CI: 71.6%-85.3%, p<0.01), HE4 (63.5%, 95%CI: 55.1%-71.9%, p<0.001) and ROMA (77.8%, 95%CI: 65.6%-89.9%, p<0.05). Particularly in FIGO Stage I patients, OCS demonstrated significant higher sensitivity than CA125 (89.7%, 95%CI: 83.0%-96.5% vs.70.1%, 95%CI: 59.9%-80.4%, p < 0.01), HE4 (51.4%, 95%CI: 39.8%-62.9%, p < 0.001) and ROMA (74.2%, 95%CI: 58.8%-89.6%, p < 0.05). The specificity of OCS was higher than CA125 and ROMA (all p<0.001), but lower than HE4 across all stage subgroups. Conclusions: This multicenter study demonstrated that the OCS is a promising non-invasive diagnostic tool for the detection of OC. Clinical trial information: NCT06366997 .