Abstract Objective: The Pancreatic Cancer Detection Consortium (PCDC) performed a blinded EDRN defined phase 2 Biomarker Bakeoff study of eight promising biomarker panels using pancreatic cancer ductal adenocarcinoma (PDAC) case and general population healthy control samples from three institutions. The scientific questions were to determine whether panels could discriminate PDAC cases from controls with Receiver Operating Characteristic Area Under the Curve (AUC) 0. 8, compare panel performance head-to-head via 95% confidence intervals (CI), and determine whether the panel improved upon serum CA19-9 alone. A secondary goal was to perform modeling to discover a new panel consisting of individual biomarkers. Methods: Eligible biomarkers were required to have had a prior EDRN defined phase 2 validation study published and be ready for validation in a sample set from multiple institutions. Three institutions submitted a total of 140 cases and 140 controls frequency matched to cases on age and sex. Four consortium member institutions submitted for validation eight panels consisting of ten plasma, serum and DNA genotyping biomarkers in addition to CA19-9. Locked panel formulas were submitted prior to specimen distribution. The primary metric was AUC with bootstrapped 95% CIs. LASSO penalized regression was used for exploratory panel building. Nested cross validation and internal-external validation were performed, and optimism-corrected performance estimates were computed. Results: The overall sample (N=280) was 51% female, median age of 67 years, and 94% were of non-Hispanic white race and ethnicity. Controls had median BMI 27. 3, 56% never smokers, and 12% type II diabetes mellitus (DM2) ; cases (staged I to IV) had median BMI 26. 6, 42% never smokers, and 26% DM2. Overall panel AUC estimates ranged from 89. 9 to 96. 3 and all were significantly larger than the null hypothesis value of 0. 8 (p0. 05). The apparent serum CA19-9 AUC was 91. 7 (87. 8, 95. 6). Two panels were significantly different from serum CA19-9, a panel with FUT2/3 genotype with serum CA19-9 (p=0. 002) and a panel containing tissue factor pathway inhibitor (TFPI), tenascin C (TNC), and plasma CA19-9 (p=0. 01). In subset analyses by PDAC stage, no panel improved upon the null hypothesis value of 0. 8 in stage I (p0. 05), all panels improved upon the null hypothesis value of 0. 8 in stage II and III (p0. 05), and only serum CA19-9 did not improve upon the null hypothesis value of 0. 8 in stage IV. All biomarkers but two microRNAs were retained in a LASSO model that had optimism corrected AUC=96. 4 (95% CI: 94. 0, 98. 9). Conclusions: All submitted panels performed well overall in this blinded study, with the panel containing FUT2/3 genotype performing the best. Panel discovery improved upon serum CA19-9, though optimism corrected AUC 95% CIs overlap with those of apparent CA19-9 performance. Further work is needed to prioritize promising biomarkers and to improve detection of early stage PDAC. Citation Format: Ann L. Oberg, William R. Bamlet, Grant Izmirlian, Seetharaman Balasenthil, Surinder K. Batra, Masataka Hayashi, Daniel Herman, Michael A. Hollingsworth, Maneesh Jain, Ann M. Killary, Brianna M. Krusen, Suyu Liu, Gopalakrishnan Natarajan, Subrata Sen, Lynette M. Smith, Sudhir Srivastava, Brian M. Wolpin, Kenneth S. Zaret, Michael G. Goggins. Pancreatic Cancer Detection Consortium biomarker bake-off: A consortium Phase 2 blinded biomarker validation and panel discovery study 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 (18Suppl₃): Abstract nr B070.
Oberg et al. (Sun,) studied this question.