The evolving role of neoadjuvant immunotherapy in resectable non-small cell lung cancer: a narrative review.

[BACKGROUND AND OBJECTIVE] The historical management of resectable non-small cell lung cancer (NSCLC) has relied on surgical resection and adjuvant chemotherapy, an approach with unsatisfactory long-term survival due to high rates of recurrence and micrometastasis. This narrative review synthesizes the evidence for a paradigm shift to neoadjuvant immunotherapy, which administers systemic therapy prior to surgery to address both the primary tumor and subclinical micrometastatic disease.

[METHODS] A comprehensive review was conducted on PubMed, Embase, and Scopus, limited to English-language articles from 2018 to the present to ensure a focus on recent, pivotal Phase II and III randomized clinical trials. The search used keywords such as 'neoadjuvant immunotherapy', 'resectable NSCLC', and 'biomarkers' to identify relevant studies.

[KEY CONTENT AND FINDINGS] Initial immune checkpoint inhibitor (ICI) monotherapy trials established feasibility and efficacy. Large-scale phase III trials like CheckMate 816 and AEGEAN have since established neoadjuvant chemo-immunotherapy as the new standard of care, demonstrating significant improvements in pathological complete response (pCR), event-free survival (EFS), and overall survival (OS). This has validated pathological response as a surrogate endpoint for long-term survival, which accelerates drug development. The review also highlights novel combinations like antibody-drug conjugates (ADCs) in trials such as NeoCOAST-2, which have shown high pathological response rates, and discusses the evolution of biomarkers from programmed death-ligand 1 (PD-L1) to the more dynamic circulating tumor DNA (ctDNA).

[CONCLUSIONS] Neoadjuvant immunotherapy has fundamentally transformed the treatment landscape for resectable NSCLC, establishing a definitive paradigm shift from conventional surgery-first approaches and becoming a foundational component of modern multidisciplinary care with a promising trajectory toward improved long-term outcomes and the realization of minimal residual disease (MRD) guided therapy. Challenges remain, including the need for better predictive biomarkers, optimized regimens, and management of surgical complexities.