The impact of residual multi-level N2 disease after induction therapy for non-small cell lung cancer

Background: The presence of residual N2 disease following induction therapy for locally advanced non-small cell lung cancer (NSCLC) has been proposed as a contraindication to surgery. However, single level N2 metastases found in the operative specimens of patients with clinical N0 NSCLC who did not receive induction therapy is associated with prolonged survival. In order to investigate whether residual single level N2 disease following induction therapy was similarly associated with prolonged survival, we conducted a retrospective review of patients with stages IIIa and IIIb NSCLC who had undergone induction therapy followed by surgery. Methods: A retrospective review was performed of the hospital records of patients with stages IIIa and IIIb NSCLC who had undergone induction therapy consisting of chemotherapy and/ or radiotherapy followed by tumor resection and mediastinal lymph node dissection at 11 Japanese national referral hospitals. Survival was analyzed by the Kaplan-Meier method and prognostic factors were determined by the log-rank and Cox regression methods. Results: One hundred thirty-one patients underwent induction therapy of NSCLC stages IIIa (n=95) and IIIb (n=36) followed by complete tumor resection during a 12-year interval. Clinical N2 disease was present in 114 (87%) patients and N3 disease in 17 (13%) patients. Median follow up was 48 months. Eighteen patients had residual single level N2 disease and 25 patients had multiple residual N2 level metastases. The 5-year survival was 54% for patients with pathologic single level N2 disease and 11% for patients with multiple N2 level disease (P<0.01). In a multivariate analysis, only the pathologic N status significantly influenced survival. Conclusion: Patents who have multiple levels of N2 disease have a much worse prognosis than patients who have single level of N2.