Prognostic value of CA 19-9, CEA, CRP, LDH and bilirubin levels in locally advanced and metastatic pancreatic cancer: results from a multicenter, pooled analysis of patients receiving palliative chemotherapy

J Cancer Res Clin Oncol. 2013 Apr;139(4):681-9. doi: 10.1007/s00432-012-1371-3. Epub 2013 Jan 13.


Purpose: CA 19-9 is the only established tumor marker in pancreatic cancer (PC); the prognostic role of other serum markers like CEA, CRP, LDH or bilirubin has not yet been defined.

Methods: We pooled pre-treatment data on CA 19-9, CEA, CRP, LDH and bilirubin levels from two German multicenter randomized phase II trials together with prospective patient data from one high-volume German Cancer Center. Marker levels were assessed locally before the start of palliative first-line therapy for advanced PC and serially during treatment (for CA 19-9 only). Clinical and biomarker data (overall 12 variables) were correlated with the efficacy endpoints time-to-progression (TTP) and overall survival (OS) by using uni- and multivariate Cox models.

Results: Data from 291 patients were included in this pooled analysis; 253 patients (87 %) received treatment within prospective clinical trials. Median TTP in the study cohort was 5.1 months and median OS 9.0 months. In univariate analysis, pre-treatment CA 19-9 (HR 1.55), LDH (HR 2.04) and CEA (HR 1.89) levels were significantly associated with TTP. Regarding OS, baseline CA 19-9 (HR 1.46), LDH (HR 2.07), CRP (HR 1.69) and bilirubin (HR 1.62) were significant prognostic factors. Within multivariate analyses, pre-treatment log [CA 19-9] (as continuous variable for TTP) and log [bilirubin] as well as log [CRP] (for OS) had an independent prognostic value. A CA 19-9 decline of ≥25 % during the first two chemotherapy cycles was predictive for TTP and OS, independent of the applied CA 19-9 assay.

Conclusion: Baseline CA 19-9 and CA 19-9 kinetics during first-line chemotherapy are prognostic in advanced PC. Besides that finding other serum markers like CRP, LDH and bilirubin can also provide prognostic information on TTP and OS.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bilirubin / metabolism*
  • Biomarkers, Tumor / metabolism
  • C-Reactive Protein / metabolism*
  • CA-19-9 Antigen / metabolism*
  • Carcinoembryonic Antigen / metabolism*
  • Carcinoma, Acinar Cell / drug therapy
  • Carcinoma, Acinar Cell / metabolism
  • Carcinoma, Acinar Cell / mortality
  • Carcinoma, Acinar Cell / secondary
  • Female
  • Follow-Up Studies
  • Humans
  • L-Lactate Dehydrogenase / metabolism*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Palliative Care
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / mortality*
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Prospective Studies
  • Retrospective Studies
  • Survival Rate


  • Biomarkers, Tumor
  • CA-19-9 Antigen
  • Carcinoembryonic Antigen
  • C-Reactive Protein
  • L-Lactate Dehydrogenase
  • Bilirubin