Surgery versus definitive radiotherapy after induction immunochemotherapy for stage II and III non-small cell lung cancer: A multicenter, pragmatic analysis.

Abstract

Induction immunochemotherapy is the standard of care for resectable stage II and III non-small cell lung cancer. However, the comparative effectiveness of subsequent definitive surgery versus radiotherapy remains uncertain. We aimed to compare outcomes between these 2 strategies in routine clinical practice. This multicenter, retrospective cohort study included patients with stage II and III non-small cell lung cancer who received induction immunochemotherapy followed by surgery or definitive radiotherapy across 12 centers in China. Propensity score matching (1:2) was used to balance clinicopathological characteristics. The primary end point was progression-free survival; secondary end points included overall survival and recurrence patterns. Among 967 patients (683 surgery; 284 radiotherapy), the matched intent-to-treat cohort included 548 patients (365 surgery; 183 radiotherapy). Compared with radiotherapy, surgery was associated with significantly longer progression-free survival (hazard ratio, 0.32; 95% CI, 0.23-0.44; P < .001) and overall survival (hazard ratio, 0.41; 95% CI, 0.26-0.66; P < .001). Surgery reduced overall recurrence (-21.3%; 95% CI, -31.1 to -11.3) and local recurrence (-17.5%; 95% CI, -25.0 to -9.9), but did not affect distant metastasis. In the subgroup of patients for whom pneumonectomy was indicated, surgery improved progression-free survival (hazard ratio, 0.47; 95% CI, 0.26-0.85; P = .013) but did not confer an overall survival benefit (hazard ratio, 1.14; 95% CI, 0.48-2.70; P = .76). Among patients who achieved a clinical complete response, outcomes were similar between the 2 groups. Definitive surgery after induction immunochemotherapy offers superior progression-free survival and overall survival compared with definitive radiotherapy, primarily driven by improved local control. For patients requiring pneumonectomy or achieving a clinical complete response, treatment should be individualized, and prospective trials are warranted.