Perioperative strategies for resectable EGFR-Mutant NSCLC: evidence hierarchy and clinical decision-making

The management of resectable non-small cell lung cancer (NSCLC) with EGFR-sensitizing mutations has changed substantially over the past decade, with adjuvant osimertinib now representing the most mature perioperative strategy because it has demonstrated durable disease-free survival, overall survival, and central nervous system (CNS) benefit in ADAURA. This review examines resectable EGFR-mutant NSCLC through the lens of evidence maturity rather than novelty, emphasizing the biologic features that distinguish this subgroup from unselected NSCLC, including CNS tropism, limited perioperative immunotherapy efficacy, and the distinct interpretability of pathologic response under EGFR-tyrosine kinase inhibitor (TKI) therapy. We compare established and emerging perioperative approaches, including aumolertinib, furmonertinib, befotertinib, and neoadjuvant or perioperative osimertinib-based strategies, while underscoring that encouraging early signals should not be equated with established survival benefit before mature event-free survival or overall survival data are available. We also address three unresolved questions: the role of adjuvant chemotherapy in the osimertinib era, the extent to which targeted therapy should move into the neoadjuvant setting, and whether minimal residual disease assessment may eventually support treatment personalization. Overall, current evidence supports adjuvant osimertinib as the reference standard for resected EGFR-mutant NSCLC, whereas other third-generation adjuvant TKIs and perioperative targeted strategies remain promising but should be interpreted according to the maturity of their supporting data and the presence or absence of overall survival benefit.