Clinical impact of local consolidative therapy in EGFR-mutant metastatic NSCLC: A propensity-matched multicenter analysis

Abstract

Objectives To evaluate the impact of consolidative surgery and radiotherapy (RT) on survival outcomes in patients with advanced or metastatic epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). Methods This retrospective, multicenter cohort study included 864 patients with EGFR-mutant advanced or metastatic NSCLC receiving first-line EGFR-TKIs. Patients were categorized into EGFR-TKI monotherapy (n = 616), TKI plus surgery (n = 100), and TKI plus RT (n = 148). Propensity score matching (PSM) and overlap weighting were applied to balance baseline characteristics. Overall survival (OS) and progression-free survival (PFS) were analyzed using Cox proportional hazards models and restricted mean survival time (RMST). Results After PSM, 97 matched pairs were generated for TKI versus TKI plus surgery and 148 pairs for TKI versus TKI plus RT. Compared with TKI alone, consolidative surgery significantly improved OS (hazard ratio [HR], 0.36; 95% CI, 0.20-0.65; p < 0.001) and PFS (HR, 0.48; 95% CI, 0.34-0.67; p < 0.001), with RMST gains of 10.7 and 10.6 months.Consolidative RT showed a trend toward longer OS (HR, 0.61; 95% CI, 0.39-0.93; p = 0.023)without significant PFS or consistent RMST benefit. Subgroup analyses showed surgery benefit in younger patients with good performance, lower metastatic burden, and no brain metastasis, whereas RT effects were heterogeneous. Conclusion In this real-world cohort, consolidative surgery combined with EGFR-TKI was associated with a clear survival benefit in advanced EGFR-mutant NSCLC while the effect of consolidative RT was less consistent, highlighting the importance of careful patient selection and multidisciplinary management.