Local consolidative therapy after EGFR-TKI response in advanced EGFR-mutant NSCLC

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have markedly improved outcomes in advanced EGFR-mutant non-small cell lung cancer (NSCLC). However, durable disease control remains limited by residual disease, intratumoral heterogeneity, and evolutionary resistance. Local consolidative therapy (LCT), defined as definitive ablation of residual tumor sites after initial response to systemic therapy, has emerged as a promising strategy to prolong disease control and modify the natural history of advanced disease.In this review, based on a PubMed literature search from January 2000 to December 2025, we synthesize biological, translational, and clinical evidence supporting the integration of LCT in advanced EGFR-mutant NSCLC. Mechanistic studies implicate drug-tolerant persister cells, spatially heterogeneous resistant clones, and supportive tumor microenvironments as key drivers of treatment failure, providing a rationale for early eradication of residual lesions. Across randomized trials and real-world cohorts, LCT has consistently been associated with improved progression-free survival and, in selected patients, overall survival, without excessive toxicity.With advances in circulating tumor DNA, metabolic imaging, and molecular profiling, LCT may evolve from a morphology-based approach into a biomarker-guided precision strategy integrated with modern systemic therapy.