Pancreatic Cancer Detection Consortium Biomarker Bakeoff: A Phase II Blinded Biomarker Validation and Panel Discovery Study

Authors

• Ann L. Oberg, Mayo Clinic
• William R. Bamlet, Mayo Clinic
• Grant Izmirlian, National Institutes of Health
• Seetharaman Balasenthil, The University of Texas MD Anderson Cancer Center
• Surinder K. Batra, University of Nebraska Medical CenterFollow
• Masataka Hayashi, Johns Hopkins University School of Medicine
• Daniel S. Herman, University of Pennsylvania
• Michael A. Hollingsworth, University of Nebraska Medical CenterFollow
• Maneesh Jain, University of Nebraska Medical CenterFollow
• Ann M. Killary, The University of Texas MD Anderson Cancer Center
• Brianna M. Krusen, University of Pennsylvania
• Suyu Liu, The University of Texas MD Anderson Cancer Center
• Shounak Majumder, Mayo Clinic
• Gopalakrishnan Natarajan, University of Nebraska Medical Center
• Subrata Sen, The University of Texas MD Anderson Cancer Center
• Lynette M. Smith, University of Nebraska Medical CenterFollow
• Sudhir Srivastava, National Institutes of Health
• Brian M. Wolpin, Dana-Farber Cancer Institute and Harvard Medical School
• Kenneth S. Zaret, University of Pennsylvania
• Michael G. Goggins, Johns Hopkins University School of Medicine

Document Type

Article

Journal Title

Clinical Cancer Research

Publication Date

2026

Volume

32

Abstract

PURPOSE: The Pancreatic Cancer Detection Consortium (PCDC) performed a blinded Early Detection Research Network-defined phase II biomarker bakeoff study of blood-based biomarker panels. The aims were to evaluate panel performance, to compare the panels' performance with that of cancer antigen 19-9 (CA19-9) alone, and to evaluate the performance of new combinations of the individual biomarkers.

EXPERIMENTAL DESIGN: Ten biomarkers representing eight biomarker panels and CA19-9 were evaluated using plasma, serum, and germline DNA from 140 stage I to IV pancreatic ductal adenocarcinoma (PDAC) cases and 140 controls from three tertiary care institutions, with controls frequency matched to cases on age and sex. LASSO regression was employed to explore new biomarker combinations. The primary metric was area under the receiver operating characteristic curve (AUC).

RESULTS: The study population was 51% female, with median age 67.3 (minimum: 45, maximum: 90) years. Biomarker panel AUCs ranged from 89.9 to 96.3; the AUC for serum CA19-9 alone was 91.7 [95% confidence interval (CI), 87.8-95.6]. Two panels had significantly higher AUCs than serum CA19-9 alone, the CA19-9/FUT2/3 panel (AUC = 96.3, P = 0.002), and the tissue factor pathway inhibitor/tenascin C (TFPI/TNC-FNIII-C) panel (AUC = 95, P = 0.01). Exploratory models to recombine biomarkers retained all but two biomarkers [optimism-corrected AUC = 96.4 (94-98.9)].

CONCLUSIONS: The CA19-9/FUT2/3 panel was the best performing panel in this biomarker bakeoff. Its evaluation in larger studies is warranted. Biomarker bakeoffs are an effective strategy for comparing the performance of promising biomarkers for pancreatic cancer early detection, and the PCDC is well poised to conduct such studies. Recommendations for performing such studies are provided.

MeSH Headings

Humans, Biomarkers, Tumor, Pancreatic Neoplasms, Female, Aged, Carcinoma, Pancreatic Ductal, Male, Middle Aged, CA-19-9 Antigen, Early Detection of Cancer, Aged, 80 and over, ROC Curve, Neoplasm Staging, Case-Control Studies

ISSN

1557-3265

DOI Link

10.1158/1078-0432.CCR-25-4061

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Oberg, Ann L.; Bamlet, William R.; Izmirlian, Grant; Balasenthil, Seetharaman; Batra, Surinder K.; Hayashi, Masataka; Herman, Daniel S.; Hollingsworth, Michael A.; Jain, Maneesh; Killary, Ann M.; Krusen, Brianna M.; Liu, Suyu; Majumder, Shounak; Natarajan, Gopalakrishnan; Sen, Subrata; Smith, Lynette M.; Srivastava, Sudhir; Wolpin, Brian M.; Zaret, Kenneth S.; and Goggins, Michael G., "Pancreatic Cancer Detection Consortium Biomarker Bakeoff: A Phase II Blinded Biomarker Validation and Panel Discovery Study" (2026). Journal Articles: Biochemistry & Molecular Biology. 186.
https://digitalcommons.unmc.edu/com_bio_articles/186