Induction Chemotherapy versus Chemoradiotherapy for Stage III Non-small Cell Lung Cancer

Reviewer: Nathan Jones DO
Abramson Cancer Center of the University of Pennsylvania
Last Modified: September 23, 2008

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Presenter: Kristin Higgins
Presenter's Affiliation: Duke University, North Carolina
Type of Session: Scientific


  • Stage IIIa non-small cell lung cancer with N2 disease represents a heterogenous group of patients ranging from microscopic lymph node involvement on staging mediastinoscopy to bulky mediastinal disease on initial staging
  • The optimal treatment for these patients remains controversial
  • As surgery alone has shown poor outcomes, pre-operative treatment appears to be more efficacious
  • There is no consensus of the superiority of chemotherapy alone versus chemoradiation in the neoadjuvant setting
  • This study sets out to compare these two approaches and to identify subgroups that may benefit from the more aggressive chemoradiation approach

Materials and Methods

  • Retrospective analysis of 101 patients treated at Duke from 1995-2006
  • All patients with pathologically demonstrated N2 disease
  • All patients underwent induction therapy consisting of chemotherapy alone or chemoradiation, in anticipation of definitive surgery
  • Multivariate analysis was performed to assess the effect of various factors on overall survival, disease-free survival and local control
  • Kaplan-Meier curves were utilized to compare local control, disease-free survival, and overall survival


  • 101 patients were included in the analysis, with approximately 2/3 receiving chemoradiation
  • 3-year overall survival was 40% for all patients, with no significant difference between those receiving chemotherapy alone or chemoradiation
  • Pathologic complete response (CR) rate was 65% vs 35%, favoring those receiving chemoradiation
  • Post-operative mortality was 5% in both groups
  • There was a trend towards those patients receiving chemoradiation being more likely to ultimately undergo resection (84% vs 69% of those receiving chemotherapy alone, p=0.1)
  • All patients receiving neoadjuvant therapy were included in the analysis, regardless of whether or not surgery was ultimately performed
  • Bronchopleural fistula occurred in 7% of chemoradiation patients vs 0% of chemotherapy patients, but this did not reach statistical significance (p=0.27)
  • Multivariate analysis demonstrated that pathologic CR was significantly associated with local control and disease-free survival, but not overall survival
  • 3-year overall survival for macroscopic vs microscopic N2 disease was 48% vs 32% (p=0.2)
  • Overall survival curves among patients with lymph nodes ≥ 1cm appeared to separate favoring chemoradiation, but did not reach statistical significance (p=0.22), while among patients with lymph nodes < 1cm, the trend was in favor of chemotherapy (p=0.12)

Author's Conclusions

  • These data demonstrate no clinically significant difference in outcomes for patients with stage IIIa N2 non-small cell lung cancer based on pre-operative treatment
  • No subgroup was identified which would benefit from the combined modality approach
  • Pre-operative chemoradiation did appear to offer improved pathologic CR rate, which correlated with disease-free survival and local control, but not overall survival

Clinical/Scientific Implications

  • Optimal treatment of stage III non-small cell lung cancer remains controversial
  • EORTC 08941 demonstrated similar 5-year overall survival for patients treated with neoadjuvant chemotherapy and randomized to surgery versus definitive radiation therapy, with the suggestion that forgoing surgery results in decreased morbidity
  • These data are limited by the retrospective nature of the study, uneven sized arms, and the great potential for treatment bias between the two groups
  • Additional data are necessary before one can support the practice of categorical omission of radiation in the neoadjuvant setting for stage IIIa NSCLC patients

Significant improvement in progression free survival for non-small-cell lung cancer patients

Jul 7, 2011 - Erlotinib is superior to chemotherapy for improving progression free survival in patients with non-small-cell lung cancer and epidermal growth factor receptor mutations, with acceptable toxicity, according to a study presented at the 14th World Conference on Lung Cancer, hosted by the International Association for the Study of Lung Cancer and held from July 3 to 7 in Amsterdam, Netherlands.

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