Induction chemoimmunotherapy with surgery versus concurrent chemoradiation followed by immunotherapy for stage III-N2 non–small cell lung cancer

Abstract

ObjectiveDespite the growing relevance of immunotherapy for non–small cell lung cancer (NSCLC), there is limited consensus on the optimal treatment strategy for locally advanced NSCLC. This study evaluated the overall survival of patients with stage III-N2 NSCLC undergoing induction chemoimmunotherapy with surgery (CT/IO+Surgery) and definitive concurrent chemoradiation followed by immunotherapy (cCRT+IO). MethodsPatients with cT1-3, N2, M0 NSCLC in the National Cancer Database (2013 to 2019) were included and stratified by treatment regimen: CT/IO+Surgery or cCRT+IO. Overall survival was evaluated using Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching on 10 prognostic variables. ResultsOf the 3382 patients who met the study eligibility criteria, 3289 (97.3%) received cCRT+IO and 93 (2.8%) received CT/IO+Surgery. The 3-year overall survival of the entire cohort was 58.2% (95% CI, 56.2% to 60.1%). Multivariable-adjusted Cox proportional hazards modeling demonstrated better survival after CT/IO+Surgery than after cCRT+IO (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.32 to 0.84; P = .007). In a 3:1 variable ratio propensity score-matched analysis of 223 patients who received cCRT+IO and 76 patients who received CT/IO+Surgery, 3-year overall survival was 63.2% (95% CI, 55.9% to 70.2%) after cCRT+IO and 77.2% (95% CI, 64.6% to 85.7%) after CT/IO+Surgery (P = .029). ConclusionsIn this national analysis, multimodal treatment including immunotherapy was associated with a 3-year overall survival rate of 58.2% for all patients with stage III-N2 NSCLC and 77.2% for patients who underwent chemoimmunotherapy followed by surgery. These results should be considered hypothesis-generating and demonstrate the importance of developing a randomized trial to evaluate the role of surgery versus chemoradiation for locally advanced NSCLC in the modern immunotherapy era.