Abstract B054: A methylation specific PCR multi-cancer early detection (MCED) test detects pancreatic cancer

Abstract Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with limited treatment options when detected in an advanced stage. PDAC presents few signs or symptoms during early stages and is typically (73%) not diagnosed until stages III and IV. DNA methylation changes occur early in PDAC development and represent an ideal epigenetic target to develop new minimally invasive approaches for cancer detection. This study evaluated the ability of EPISEEK®, a laboratory-developed test (LDT) for multi-cancer early detection (MCED) using peripheral blood, to detect pancreatic ductal adenocarcinoma (PDAC) across different disease stages. Methods: We conducted a retrospective study consisting of sixty-two banked plasma samples, with as little as 0.4 ml collected in either EDTA or Streck cfDNA tubes from patients diagnosed with stage I, II, III, or IV PDAC. The control group consisted of blood samples from 201 asymptomatic donors (Streck tubes) with no known disease. Cell-free DNA was isolated from banked plasma and the EPISEEK assay performed. The qRT-PCR results from the 201 control cases with no known history of cancer were used to establish a reference range for each biomarker within the EPISEEK gene panel and to train a multivariate qualitative classifier. The methylation signal between the control and case groups was compared using the Mann-Whitney U test with a p >0.05 being significant. Results: Of the EDTA tube specimens, 6/8 Stage I (75%), 11/17 Stage II (65%), and 4/4 Stage IV (100%) were positive. Of the Streck tube specimens, 2/8 Stage I (25%), 5/6 Stage II (83%), 4/4 Stage III (100%), and 14/15 Stage IV (93%) were positive. Among 201 asymptomatic donor controls, one tested positive, corresponding to a specificity of 99.5%. Conclusions: Taken together, these data demonstrate that the EPISEEK assay has favorable diagnostic performance across all stages of pancreatic cancer, including early-stage disease, using either EDTA or Streck collection tubes. The clinically validated EPISEEK MCED test demonstrated combined 61.5% sensitivity and 99.5% specificity for Stages I/II PDAC which is particularly strong for detecting early-stage pancreatic cancer, as compared to current screening modalities. Additional studies are warranted. Citation Format: Richard A. Bernert, Geoffrey D. Block, Kimberly J. Bussey, William E. Fisher, Marc M. Oshiro, Thi H. Pham, Joshua Routh, Matthew Rounseville, Alejandro Zulbaran-Rojas, Mark A. Nelson. A methylation specific PCR multi-cancer early detection (MCED) test detects pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B054.