Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer

J Clin Oncol. 2011 Apr 20;29(12):1556-63. doi: 10.1200/JCO.2010.28.7045. Epub 2011 Mar 21.


Purpose: Lung cancer is the leading cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC) lacks validated biomarkers to predict treatment response. This study investigated whether circulating tumor cells (CTCs) are detectable in patients with NSCLC and what their ability might be to provide prognostic information and/or early indication of patient response to conventional therapy.

Patients and methods: In this single-center prospective study, blood samples for CTC analysis were obtained from 101 patients with previously untreated, stage III or IV NSCLC both before and after administration of one cycle of standard chemotherapy. CTCs were measured using a semiautomated, epithelial cell adhesion molecule-based immunomagnetic technique.

Results: The number of CTCs in 7.5 mL of blood was higher in patients with stage IV NSCLC (n = 60; range, 0 to 146) compared with patients with stage IIIB (n = 27; range, 0 to 3) or IIIA disease (n = 14; no CTCs detected). In univariate analysis, progression-free survival was 6.8 v 2.4 months with P < .001, and overall survival (OS) was 8.1 v 4.3 months with P < .001 for patients with fewer than five CTCs compared with five or more CTCs before chemotherapy, respectively. In multivariate analysis, CTC number was the strongest predictor of OS (hazard ratio [HR], 7.92; 95% CI, 2.85 to 22.01; P < .001), and the point estimate of the HR was increased with incorporation of a second CTC sample that was taken after one cycle of chemotherapy (HR, 15.65; 95% CI, 3.63 to 67.53; P < .001).

Conclusion: CTCs are detectable in patients with stage IV NSCLC and are a novel prognostic factor for this disease. Further validation is warranted before routine clinical application.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / analysis
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Adhesion Molecules / analysis
  • Disease-Free Survival
  • England
  • Female
  • Humans
  • Immunomagnetic Separation
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / drug effects
  • Neoplastic Cells, Circulating / immunology
  • Neoplastic Cells, Circulating / pathology*
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome


  • Biomarkers, Tumor
  • Cell Adhesion Molecules