The Significance of Upfront Knowledge of N2 Disease in Non-small Cell Lung Cancer

Previous literature suggests that patients with non-small cell lung cancer (NSCLC) and unsuspected N2 disease (cN0, pN2) represent a distinct subgroup associated with improved overall survival compared to patients with N2 disease identified prior to resection (cN2, pN2). Retrospective analysis of the National Cancer Database of patients from 2004 to 2011 with cN0 and cN2 status found to be pathologic stage III-N2 NSCLC after surgical resection. Comparison of 5-year survival of patients with unsuspected N2 disease versus those with known N2 disease after surgical resection using Kaplan-Meier analysis was made. The independent effect of unsuspected N2 disease on mortality was analyzed using multivariate analysis. A total of 3271 patients with pathologic stage III-N2 NSCLC underwent curative intent surgical resection with or without adjuvant chemotherapy or chemotherapy and radiation. Unsuspected N2 disease was identified in 48% of patients. Patients with unsuspected N2 disease were more likely to have T1 tumors (37 vs. 32%, p < 0.001). Unsuspected N2 disease did not impact 5-year overall survival compared with known N2 when adjuvant therapy was utilized (40 vs. 37%, p = 0.167). Multivariate analysis identified older age, higher comorbidity score, and treatment with surgery alone as independent risk factors for mortality. The presence of unsuspected N2 disease was not significant in this model. The findings of this study suggest that unsuspected N2 disease is associated with equivalent 5-year survival compared to cN2 disease when adjuvant therapy is employed. These results support the use of adjuvant chemotherapy and radiation therapy when confronted with unsuspected N2 disease after surgical resection for stage IIIA-NSCLC.