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

Gastroenterology. 2021 Mar;160(4):1373-1383.e6. doi: 10.1053/j.gastro.2020.11.052. Epub 2020 Dec 14.

Abstract

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.

Methods: 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.

Results: 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.

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

Keywords: Biomarker; Detection; Pancreatic Cancer.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • CA-19-9 Antigen / blood*
  • Diagnosis, Differential
  • Early Detection of Cancer / methods*
  • Feasibility Studies
  • Female
  • Healthy Volunteers
  • Humans
  • Liquid Biopsy / methods
  • Male
  • Mass Screening / methods*
  • Middle Aged
  • Pancreatic Cyst / blood
  • Pancreatic Cyst / diagnosis
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatitis, Chronic / blood
  • Pancreatitis, Chronic / diagnosis
  • Sensitivity and Specificity
  • United States

Substances

  • CA-19-9 Antigen