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

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 160; no. 4; pp. 1373 - 1383.e6
• Main Authors: Fahrmann, Johannes F., Schmidt, C. Max, Mao, Xiangying, Irajizad, Ehsan, Loftus, Maureen, Zhang, Jinming, Patel, Nikul, Vykoukal, Jody, Dennison, Jennifer B., Long, James P., Do, Kim-Anh, Zhang, Jianjun, Chabot, John A., Kluger, Michael D., Kastrinos, Fay, Brais, Lauren, Babic, Ana, Jajoo, Kunal, Lee, Linda S., Clancy, Thomas E., Ng, Kimmie, Bullock, Andrea, Genkinger, Jeanine, Yip-Schneider, Michele T., Maitra, Anirban, Wolpin, Brian M., Hanash, Samir
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2021
• Subjects: Aged; Biomarker; CA-19-9 Antigen - blood; Detection; Diagnosis, Differential; Early Detection of Cancer - methods; Feasibility Studies; Female; Healthy Volunteers; Humans; Liquid Biopsy - methods; Male; Mass Screening - methods; Middle Aged; Pancreatic Cancer; Pancreatic Cyst - blood; Pancreatic Cyst - diagnosis; Pancreatic Neoplasms - blood; Pancreatic Neoplasms - diagnosis; Pancreatitis, Chronic - blood; Pancreatitis, Chronic - diagnosis; Sensitivity and Specificity; United States; United States; Biomarker; CI; Lung; ROC; IPMN; Pancreatic Cancer; CP; PLCO; AUC; PDAC; CUMC; Detection; DFCI/BWH; ELISA
• ISSN: 0016-5085; 1528-0012; 1528-0012
• DOI: 10.1053/j.gastro.2020.11.052

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.