Multimodality Therapy for N2 Non-Small Cell Lung Cancer: An Evolving Paradigm

Background: Induction chemoradiation for resectable N2 non-small cell lung cancer (NSCLC) is used with the intent to optimize locoregional control, whereas induction chemotherapy given in systemic doses is meant to optimally target potential distant disease. However, the optimal preoperative treatment regimen is still unknown and practice patterns continue to vary widely. We compared multiinstitutional oncologic outcomes for N2 NSCLC from 4 experienced lung cancer treatment centers. Methods: This collaborative retrospective study unites 4 major thoracic oncology centers. Patients with N2 NSCLC undergoing surgical resection after induction chemotherapy (CxT) or concurrent chemoradiation (CxRT) were included. Primary outcomes were overall and disease-free survival (OS and DFS). Results: 822 patients were identified (CxT = 662 and CxRT = 160). There were no differences in 5-year OS (CxT 39.9% versus CxRT 42.9%, p = 0.250) nor in DFS (CxT 28.7% versus 29.8%, p = 0.207). Recurrence rates (CxT 46.8% versus CxRT 51.6%, p = 0.282) and recurrence patterns were not significantly different (Local: CxT 9.8% versus CxRT 9.7%; and Distant: CxT 30.4% versus CxRT 33.1%, p = 0.764). There was no difference in perioperative mortality. In the analyses of patients who underwent pretreatment invasive mediastinal staging (n = 555), there were still no significant differences in OS (p = 0.341) and DFS (p = 0.455) between the 2 treatment strategies. Conclusions: Both treatment strategies produce equivalent and better than expected outcomes compared with historical controls for N2 NSCLC, with no differences in recurrence patterns. How these conventional therapeutic strategies will compare with those involving immunotherapy combined with surgical locoregional disease control for N2 disease remains to be determined.