Outcomes of Surgery vs. Chemoradiotherapy in Patients with Clinical or Pathologic N3 Non-Small Cell Lung Cancer Running Head: Surgery in N3 Lung Cancer

Abstract Background As surgery is rarely recommended, there is minimal literature comparing the outcomes of surgery and chemoradiation in N3 non-small cell lung cancer (NSCLC). We examined the outcomes of definitive chemoradiation versus multimodality therapy, including surgery, for patients with clinical and pathologic N3 NSCLC. Methods The National Cancer Database (NCDB) was used to identify patients with (1) cT1-3N3M0 NSCLC and (2) cT1-3NxM0 with pN3 NSCLC who were treated with either definitive chemoradiation (CR) or surgery (S) between 2004-2015. A 1:1 propensity score-matched analysis was used to compare outcomes for both treatment groups in each analysis. The primary outcome was overall survival. Results In 935 matched patient pairs with cN3 NSCLC, S was associated with worse survival (hazard ratio [HR] 1.52; 95% confidence interval [CI] 1.12-2.05) compared to CR at 6 months, but was associated with a significant survival benefit after 6 months (HR 0.54; 95%CI 0.47-0.63) in multivariable analysis. In 281 pairs of patients with pN3 NSCLC, S had similar survival compared to CR at 6 months (HR 1.71; 95%CI 0.92-3.19), but was associated with improved survival after 6 months (HR 0.76; 95%CI 0.58-0.99). The complete resection rate was 80% and 73% for patients with cN3 and pN3 disease, respectively. Conclusion In patients with clinical or pathologic N3 NSCLC, surgery is associated with similar or worse short-term but improved long-term survival compared to chemoradiation. In a selected group of patients with N3 NSCLC, surgery may have a role in multimodal therapy.