THBS2/CA19-9 Detecting Pancreatic Ductal Adenocarcinoma at Diagnosis Underperforms in Prediagnostic Detection: Implications for Biomarker Advancement.
- Institute for Regenerative Medicine, Department of Cell and Developmental Biology, Abramson Cancer Center (Tumor Biology Program), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
- Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
- Division of Hematology-Oncology, Department of Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
- Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
- Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota. zaret@upenn.edu.
- Institute for Regenerative Medicine, Department of Cell and Developmental Biology, Abramson Cancer Center (Tumor Biology Program), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. zaret@upenn.edu.
Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed too late for effective therapy. The classic strategy for early detection biomarker advancement consists of initial retrospective phases of discovery and validation with tissue samples taken from individuals diagnosed with disease, compared to controls. Using this approach, we previously reported the discovery of a blood biomarker panel consisting of thrombospondin-2 (THBS2) and CA19-9 that together could discriminate resectable stage I and IIa PDAC as well as stages III and IV PDAC, with c-statistic values in the range of 0.96-0.97 in two Phase 2 studies. We now report that in two studies of blood samples prospectively collected from one to fifteen years prior to a PDAC diagnosis (Mayo Clinic and PLCO cohorts), THBS2 and/or CA19-9 failed to discriminate cases from healthy controls at the AUC=0.8 needed. We conclude that PDAC progression may be heterogeneous and for some individuals can be more rapid than generally appreciated. It is important that PDAC early detection studies incorporate high-risk, prospective pre-diagnostic cohorts into discovery and validation studies.