C-stage in colon cancer: implications of carcinoembryonic antigen biomarker in staging, prognosis, and management

J Natl Cancer Inst. 2011 Apr 20;103(8):689-97. doi: 10.1093/jnci/djr078. Epub 2011 Mar 18.


Background: The American Joint Committee on Cancer (AJCC) has proposed the inclusion of pretreatment serum carcinoembryonic antigen (CEA) level (C-stage) into the conventional TNM staging system of colon cancer. We assessed the prognosis of various stages of colon cancer after such an inclusion.

Methods: Data for all patients (N = 17 910) diagnosed with colonic adenocarcinoma (AJCC stages I, IIA, IIB, IIC, IIIA, IIIB, IIIC, and IV, based on TNM staging system) between January 1, 2004, and December 31, 2004, with a median follow-up of 27 months (range 0-35 months), were collected from the Surveillance, Epidemiology, and End Results database. C-stage (C0-stage = normal CEA level; C1-stage = elevated CEA level) was assigned to all patients with available CEA information (n = 9083). Multivariable analyses using Cox proportional hazards models were used to identify independent factors associated with prognosis. Prognosis of overall stages (AJCC stages I-IV and C0 or C1) was analyzed using Kaplan-Meier survival curves. All statistical tests were two-sided.

Results: C1-stage was independently associated with a 60% increased risk of overall mortality (hazard ratio of death = 1.60, 95% confidence interval = 1.46 to 1.76, P < .001). Overall survival was decreased in patients with C1-stage cancer compared with C0-stage cancer of the respective overall stages (P < .05). Similarly, decreased overall survival was noted in patients with stage I C1 cancer compared with stage IIA C0 or stage IIIA C0 cancer (P < .001), in patients with stage IIA C1 cancer compared with stage IIIA C0 (P < .001), and in patients with stage IIB C1 or stage IIC C1 cancer compared with stage IIIB C0 cancer (P < .001).

Conclusions: C-stage was an independent prognostic factor for colon cancer. The results support routine preoperative CEA testing and C-staging upon diagnosis of colon cancer and the inclusion of C-stage in the conventional TNM staging of colon cancer.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / epidemiology
  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / blood*
  • Carcinoembryonic Antigen / blood*
  • Chemotherapy, Adjuvant
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / epidemiology
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / pathology*
  • Confounding Factors, Epidemiologic
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging / methods
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Risk Factors
  • SEER Program
  • United States / epidemiology


  • Biomarkers, Tumor
  • Carcinoembryonic Antigen