Challenges and Controversies in Perioperative Immunotherapy in Early-Stage Non-small Cell Lung Cancer: An Optimistic
1Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
Abstract:
Immune checkpoint inhibitors have transformed the treatment landscape of non-small cell lung cancer (NSCLC), extending their role from metastatic to resectable disease. While neoadjuvant and adjuvant immunotherapies have each shown clinical value, recent evidence suggests that a perioperative strategy-incorporating both preoperative and postoperative immune-based treatment-may provide more consistent and durable survival benefits, especially in stage IIIA and high programmed death-ligand 1 (PD-L1)-expressing tumors. Despite concerns about feasibility and immune-related adverse events, phase III trials such as CheckMate 816, KEYNOTE-671, and AEGEAN have demonstrated that perioperative chemoimmunotherapy is both effective and tolerable in real-world practice. This review examines the rationale, clinical trial data, patient selection criteria, and safety profile of perioperative immunotherapy, and argues for its increasing adoption as a strategic standard in eligible NSCLC patients. Additionally, emerging biomarkers and circulating tumor DNA-based minimal residual disease surveillance hold promise for refining precision of perioperative treatment. Taken together, the evidence supports perioperative immunotherapy as a forward-looking, evidence-based approach to improving outcomes in resectable NSCLC.
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