Detection of Pancreatic Cancer Using a Methylation-Specific PCR-Based Multi-Cancer Early Detection Test

Abstract

ContextPancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy often diagnosed at advanced stages due to the lack of early clinical symptoms. DNA methylation alterations arise early in PDAC tumorigenesis and may serve as promising biomarkers for blood-based cancer detection. ObjectiveTo evaluate the performance of EPISEEK, a laboratory-developed blood-based multi-cancer early detection (MCED) assay, for detecting PDAC across disease stages. DesignA retrospective cohort study included 97 patients with stage I-IV PDAC and 201 asymptomatic healthy controls. Sensitivity, specificity, area under the curve (AUC), and stage-specific performance were assessed. EPISEEK-MCED performance was also compared with CA 19-9 alone and in combination with CA 19-9. ResultsEPISEEK-MCED classified 65 of 97 PDAC cases as positive, corresponding to an observed sensitivity of 70.1% (95% CI, 60.3% - 78.3%) at 99.5% specificity. The assay demonstrated strong discrimination between PDAC cases and healthy controls, with an AUC of 0.916 (95% CI, 0.88 - 0.952). Sensitivity increased with advancing stage while remaining substantial in early-stage disease, measuring 53.6% for stage I and 65.1% for stage II PDAC, 100% for stage III and 94.7% for stage IV. Across stages, EPISEEK-MCED outperformed CA 19-9 alone, particularly in early-stage disease. Combined analysis of EPISEEK-MCED and CA 19-9 further improved detection performance, achieving sensitivity of 57.1% and 81.4% for stage I and II, respectively. ConclusionsEPISEEK-MCED demonstrated high specificity and sensitivity for PDAC detection across disease stages, including early-stage disease. Combining EPISEEK-MCED with CA19-9 further improved performance, supporting its clinical utility for PDAC detection.