Implications of CA19-9 elevation for survival, staging, and treatment sequencing in intrahepatic cholangiocarcinoma: A national cohort analysis

J Surg Oncol. 2016 Sep;114(4):475-82. doi: 10.1002/jso.24381. Epub 2016 Jul 20.


Background: Optimal management of patients with intrahepatic cholangiocarcinoma (ICCA) and elevated CA19-9 remains undefined. We hypothesized CA19-9 elevation above normal indicates aggressive biology and that inclusion of CA19-9 would improve staging discrimination.

Methods: The National Cancer Data Base (NCDB-2010-2012) was reviewed for patients with ICCA and reported CA19-9. Patients were stratified by CA19-9 above/below normal reference range. Unadjusted Kaplan-Meier and adjusted Cox-proportional-hazards analysis of overall survival (OS) were performed.

Results: A total of 2,816 patients were included: 938 (33.3%) normal; 1,878 (66.7%) elevated CA19-9 levels. Demographic/pathologic and chemotherapy/radiation were similar between groups, but patients with elevated CA19-9 had more nodal metastases and less likely to undergo resection. Among elevated-CA19-9 patients, stage-specific survival was decreased in all stages. Resected patients with CA19-9 elevation had similar peri-operative outcomes but decreased long-term survival. In adjusted analysis, CA19-9 elevation independently predicted increased mortality with impact similar to node-positivity, positive-margin resection, and non-receipt of chemotherapy. Proposed staging system including CA19-9 improved survival discrimination over AJCC 7th edition.

Conclusion: Elevated CA19-9 is an independent risk factor for mortality in ICCA similar in impact to nodal metastases and positive resection margins. Inclusion of CA19-9 in a proposed staging system increases discrimination. Multi-disciplinary therapy should be considered in patients with ICCA and CA19-9 elevation. J. Surg. Oncol. 2016;114:475-482. © 2016 Wiley Periodicals, Inc.

Keywords: CA19-9; biologic resectability; biomarker; cholangiocarcinoma.

MeSH terms

  • Aged
  • Bile Duct Neoplasms / blood
  • Bile Duct Neoplasms / mortality
  • Bile Duct Neoplasms / pathology
  • Bile Duct Neoplasms / therapy*
  • CA-19-9 Antigen / blood*
  • Cholangiocarcinoma / blood
  • Cholangiocarcinoma / mortality
  • Cholangiocarcinoma / pathology
  • Cholangiocarcinoma / therapy*
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Proportional Hazards Models


  • CA-19-9 Antigen