Prognostic and predictive role of epidermal growth factor receptor mutation in recurrent pulmonary adenocarcinoma after curative resection

Eur J Cardiothorac Surg. 2015 Mar;47(3):556-62. doi: 10.1093/ejcts/ezu177. Epub 2014 Apr 22.

Abstract

Objectives: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment prolongs the progression-free survival of patients with advanced non-small-cell lung cancer harbouring EGFR mutations. This study aimed to evaluate the prognostic factors influencing survival after recurrence, and the effectiveness of EGFR-TKIs in patients with recurrent pulmonary adenocarcinoma after curative resection.

Methods: EGFR mutations were prospectively evaluated in 594 patients who underwent curative surgical resection for pulmonary adenocarcinoma. Among them, 138 patients who had postoperative recurrent disease were enrolled in the study. Potential prognostic factors for post-recurrence survival (PRS) were evaluated, and predictive factors of responsiveness to EGFR-TKIs were also analysed.

Results: Among the 138 patients who had postoperative recurrent disease, EGFR mutations were identified in 73 (52.9%) patients. In multivariable analysis, never-smoking status [hazard ratio (HR), 0.522; P = 0.012], adjuvant radiotherapy (HR, 1.995; P = 0.016), disease-free interval of less than 1 year from initial resection to recurrence (HR, 2.382; P = 0.001), surgical treatment for recurrence (HR, 0.346; P = 0.002) and EGFR mutation (HR, 0.552; P = 0.013) were independent prognostic factors for PRS. Among patients treated with EGFR-TKI, EGFR mutation status was the only predictor of response to EGFR-TKI (P < 0.001), and patients with EGFR mutation showed better PRS (3- and 5-year survival rates after recurrence, 68.8 and 41.1%, respectively) than those without EGFR mutations (3- and 5-year survival rates after recurrence, 39.1 and 15.7%, respectively; P = 0.017).

Conclusions: Our study demonstrated that EGFR mutation is an independent prognostic factor for PRS. Considering that EGFR mutations were the only independent predictors for response to EGFR-TKIs, selecting patients for EGFR-TKI therapy according to EGFR mutation status may lead to a better prognosis in patients with recurrent pulmonary adenocarcinoma.

Keywords: Adenocarcinoma of lung; Biological; Epidermal growth factor; Mutation; Receptor; Recurrence; Thoracic surgery; Tumour markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / surgery*
  • Adenocarcinoma of Lung
  • Aged
  • Biomarkers, Tumor / genetics
  • Disease-Free Survival
  • ErbB Receptors / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / surgery*
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Recurrence, Local / enzymology
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / surgery*
  • Prognosis
  • Retrospective Studies

Substances

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