Abstract B043: Extracellular vesicle and particle assay for ovarian cancer: Performance before and at Diagnosis

Abstract Introduction: Many promising biomarkers and methods for cancer screening ultimately fail because initial evaluations are conducted in cohorts of symptomatic patients or those with advanced-stage disease, rather than the intended average-risk population. Consequently, these tests often demonstrate reduced performance when later validated in appropriate screening cohorts. Here, we compared the performance of an extracellular vesicle and particle (EVP) based blood test for ovarian cancer (OC) with the established biomarker CA125 across two independent and clearly defined cohorts: women diagnosed with ovarian cancer proximal to the time of sample collection (UKOPS, United Kingdom Ovarian Cancer Population Study), and women with no known risk of ovarian cancer whose samples were collected up to 12 months prior to clinical diagnosis (UKCTOCS, United Kingdom Collaborative Trial of Ovarian Cancer). Control samples were obtained from women who remained ovarian cancer-free throughout the UKCTOCS trial follow-up period. Methods: The EVP-based blood test was previously locked (EVP analytes, method, cutoff). We evaluated the EV based test and CA125 in two blinded case-control studies nested within UKOPS and UKCTOCS. In study 1, cases were all women with a diagnosis or suspicion of ovarian cancer at sample donation from UKOPS with controls randomly selected from woman >= 50 yrs. In study 2, cases were all women who developed high grade serous ovarian cancer (HGSOC) within 12 months following sample donation from UKCTOCS (no screening and annual ultrasound screening arms), cases were matched by age at collection (+/-2 years) to women who had no OC detected (Controls). The EVP-based test was run with a locked method and classifier algorithm utilizing three independent biomarker combinations. A commercially available CA125 immunoassay was run with a previously established cutoff (15.5 U/mL). Results: In cases from women with a diagnosis or suspicion of OC from study 1, the sensitivity of the EV-based test for HGSOC was 97% (64/66, 95% CI 93-100), the sensitivity of CA125 was 86% (57/66, 95% CI 78-95). In cases from women who went on to develop HGSOC within 12 months from study 2, the sensitivity of the EVP-based test was 83% (34/41, 95% CI 71-94), the sensitivity of CA125 was 68% (28/41, 95% CI 54-83). Between both studies, the EVP-based test detected 8 additional stage I/II cases (UKOPS: 5, UKCTOCS: 3) and 5 additional stage III/IV (UKOPS: 2, UKCTOCS: 3) HGSOC cases compared to CA125. In control samples, performance remained consistent between both studies, with the EV-based test demonstrating higher specificity (Study 1 97.0%, Study 2: 97.7%) compared to CA125 (Study 1 95.5%, Study 2: 95.6%). Conclusion: The EV-based blood test consistently outperforms CA125 in detecting both early- and late-stage ovarian cancers, in samples collected at diagnosis as well as up to one year prior to diagnosis. The improved sensitivity and consistently higher specificity compared to CA125, underscores its potential as a screening or diagnostic tool for average-risk women. Citation Format: Brendan Manning, Sanchari Banerjee, Troy B. Hawkins, Michael Smith, Sophia Apostolidou, Aleksandra Gentry-Maharaj, Usha Menon, Dawn R. Mattoon. Brendan Manning, Sanchari Banerjee, Troy B. Hawkins, Michael M. Smith, Sophia Apostolidou, Aleksandra Gentry-Maharaj, Usha Menon, Dawn R. Mattoon. Extracellular vesicle and particle assay for ovarian cancer: Performance before and at Diagnosis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr B043.