Neoadjuvant Chemoimmunotherapy Followed by Surgery for Non-Small Cell Lung Cancer: Current Evidence and Unmet Needs

Neoadjuvant chemoimmunotherapy (nCIT) has rapidly emerged as a transformative treatment strategy for resectable non-small cell lung cancer. This review summarizes current clinical evidence, surgical considerations and ongoing challenges in incorporating nCIT into clinical practice.

A narrative review of pivotal phase II-III clinical trials was conducted, including CheckMate 816, KEYNOTE-671, AEGEAN and CheckMate 77 T, as well as recent meta-analyses and real-world evidence. Outcomes such as pathological complete response, major pathological response, event-free survival and surgical safety were evaluated. Key controversies-including patient selection, biomarker utility, surgical complexity and the role of adjuvant immunotherapy-were also examined.

Phase III trials consistently demonstrated that nCIT improves pathological complete response, major pathological response and event-free survival compared with chemotherapy alone, without increasing perioperative morbidity or mortality. Nonetheless, challenges remain in defining the optimal candidates for nCIT (particularly stage II disease, multi-station N2, for epidermal growth factor receptor-mutant tumours and programmed death-ligand 1-negative tumours). Surgical concerns include nodal fibrosis and altered hilar anatomy; however, major trials have confirmed high R0 resection rates and preserved feasibility of minimally invasive approaches. Biomarker-guided strategies using programmed death-ligand 1 and circulating tumour DNA may refine treatment selection and help guide decisions on adjuvant therapy.

nCIT establishes a new standard of care for resectable non-small cell lung cancer, offering improved pathological and survival outcomes while preserving surgical safety. Future research should focus on unresolved issues such as patient selection, biomarker integration and the role of adjuvant immunotherapy to refine personalized treatment strategies.