Circulating Tumor Cells Identify Early Recurrence in Patients with Non-Small Cell Lung Cancer Undergoing Radical Resection

PLoS One. 2016 Feb 25;11(2):e0148659. doi: 10.1371/journal.pone.0148659. eCollection 2016.


Background: Surgery is the treatment of choice for patients with non-small cell lung cancer (NSCLC) stages I-IIIA. However, more than 20% of these patients develop recurrence and die due to their disease. The release of tumor cells into peripheral blood (CTCs) is one of the main causes of recurrence of cancer. The objectives of this study are to identify the prognostic value of the presence and characterization of CTCs in peripheral blood in patients undergoing radical resection for NSCLC.

Patients and methods: 56 patients who underwent radical surgery for previously untreated NSCLC were enrolled in this prospective study. Peripheral blood samples for CTC analysis were obtained before and one month after surgery. In addition CTCs were phenotypically characterized by epidermal growth factor receptor (EGFR) expression.

Results: 51.8% of the patients evaluated were positive with the presence of CTCs at baseline. A decrease in the detection rate of CTCs was observed in these patients one month after surgery (32.1%) (p = 0.035). The mean number of CTCs was 3.16 per 10 ml (range 0-84) preoperatively and 0.66 (range 0-3) in postoperative determination. EGFR expression was found in 89.7% of the patients at baseline and in 38.9% patients one month after surgery. The presence of CTCs after surgery was significantly associated with early recurrence (p = 0.018) and a shorter disease free survival (DFS) (p = .008). In multivariate analysis CTC presence after surgery (HR = 5.750, 95% CI: 1.50-21.946, p = 0.010) and N status (HR = 0.296, 95% CI: 0.091-0.961, p = 0.043) were independent prognostic factors for DFS.

Conclusion: CTCs can be detected and characterized in patients undergoing radical resection for non-small cell lung cancer. Their presence might be used to identify patients with increased risk of early recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Cohort Studies
  • ErbB Receptors / blood
  • Female
  • Humans
  • Keratins / blood
  • Longitudinal Studies
  • Lung Neoplasms / blood*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplastic Cells, Circulating / metabolism
  • Neoplastic Cells, Circulating / pathology*
  • Prognosis
  • Prospective Studies


  • Biomarkers, Tumor
  • Keratins
  • EGFR protein, human
  • ErbB Receptors

Grant support

This work was supported by Fundacion de Investigacion Basica Alenjando Otero ( (MJS). The funders had no role in study design, data collection and analyses, decision to publish or preparation of the manuscript.