Original Research Full Report: Basic and Translational—Pancreas| Volume 160, ISSUE 4, P1373-1383.e6, March 01, 2021

Lead-Time Trajectory of CA19-9 as an Anchor Marker for Pancreatic Cancer Early Detection

Published:December 14, 2020DOI:

      Background & Aims

      There is substantial interest in liquid biopsy approaches for cancer early detection among subjects at risk, using multi-marker panels. CA19-9 is an established circulating biomarker for pancreatic cancer; however, its relevance for pancreatic cancer early detection or for monitoring subjects at risk has not been established.


      CA19-9 levels were assessed in blinded sera from 175 subjects collected up to 5 years before diagnosis of pancreatic cancer and from 875 matched controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. For comparison of performance, CA19-9 was assayed in blinded independent sets of samples collected at diagnosis from 129 subjects with resectable pancreatic cancer and 275 controls (100 healthy subjects; 50 with chronic pancreatitis; and 125 with noncancerous pancreatic cysts). The complementary value of 2 additional protein markers, TIMP1 and LRG1, was determined.


      In the PLCO cohort, levels of CA19-9 increased exponentially starting at 2 years before diagnosis with sensitivities reaching 60% at 99% specificity within 0 to 6 months before diagnosis for all cases and 50% at 99% specificity for cases diagnosed with early-stage disease. Performance was comparable for distinguishing newly diagnosed cases with resectable pancreatic cancer from healthy controls (64% sensitivity at 99% specificity). Comparison of resectable pancreatic cancer cases to subjects with chronic pancreatitis yielded 46% sensitivity at 99% specificity and for subjects with noncancerous cysts, 30% sensitivity at 99% specificity. For prediagnostic cases below cutoff value for CA19-9, the combination with LRG1 and TIMP1 yielded an increment of 13.2% in sensitivity at 99% specificity (P = .031) in identifying cases diagnosed within 1 year of blood collection.


      CA19-9 can serve as an anchor marker for pancreatic cancer early detection applications.


      Abbreviations used in this paper:

      AUC (area under the curve), CI (confidence interval), CP (chronic pancreatitis), CUMC (Columbia University Irving Medical Center), DFCI/BWH (Dana-Farber Cancer Institute/Brigham and Women’s Hospital), ELISA (enzyme-linked immunosorbent assay), IPMN (intraductal papillary mucinous neoplasms), PDAC (pancreatic ductal adenocarcinoma), PLCO (Prostate), Lung (Colorectal and Ovarian Cancer Screening Trial), ROC (receiver operating characteristic curve)
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