Precision Perioperative Treatment for Resectable Non-Small Cell Lung Cancer: Current Status and Perspectives

The treatment paradigm for resectable non-small cell lung cancer (NSCLC) continues to evolve toward precision perioperative strategies. Despite curative-intent surgery, disease recurrence remains common. Adjuvant tyrosine kinase inhibitors have substantially improved disease-free survival and, in selected populations, overall survival, particularly for patients with sensitizing EGFR mutations or ALK rearrangements. Targeted therapies for other actionable genomic alterations (AGAs), including RET fusions, remain investigational. Adequate tissue acquisition and comprehensive molecular profiling before treatment initiation are therefore essential for optimal treatment selection. For patients without sensitizing EGFR mutations or ALK rearrangements, neoadjuvant or perioperative PD-(L)1 blockade combined with platinum-based chemotherapy has become a standard of care for eligible patients with resectable stage II–III NSCLC, improving pathological response, event-free survival, and, in select trials, overall survival. Multidisciplinary reassessment of resectability following neoadjuvant treatment is particularly important for borderline-resectable disease. Patients subsequently deemed unresectable require individualized management, potentially including definitive chemoradiotherapy followed by consolidation immunotherapy. Although cross-trial comparisons suggest advantages of neoadjuvant chemoimmunotherapy over adjuvant-only immunotherapy, direct randomized comparisons are lacking. The incremental benefit of postoperative immunotherapy after neoadjuvant chemoimmunotherapy remains uncertain for selected patients. Future priorities include optimizing treatment sequencing, improving pathological complete response rates, refining radiographic and molecular response assessment, investigating resistance mechanisms, and integrating circulating tumor DNA-based minimal residual disease detection into individualized postoperative treatment. Whether surgery can be safely omitted in exceptional responders also warrants prospective investigation. Together, these advances support a biomarker-driven, response-adapted approach to precision perioperative NSCLC management.