Immunotherapy in resectable non–small cell lung cancer; emerging clinical questions

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Background Recurrence after curative resection remains common in resectable non–small cell lung cancer (NSCLC), reflecting the persistence of micrometastatic disease. Conventional perioperative platinum-based chemotherapy provides only a modest survival benefit. Immune checkpoint inhibitors (ICIs) have recently transformed the peri-surgical treatment landscape. Highlights This review summarizes evidence from phase 3 peri-surgical immunotherapy trials in resectable NSCLC and discusses emerging clinical, surgical, and biological questions, including criteria for resectability, the role of conversion surgery, the value of postoperative immunotherapy, and biomarker-driven treatment strategies. Adjuvant ICI trials have shown mixed results, whereas neoadjuvant and perioperative approaches have consistently improved survival outcomes. Concerns regarding surgical delay, increased operative complexity, and perioperative morbidity appear manageable. Modern systemic therapy is reshaping the concept of resectability, necessitating integration of anatomic, clinical, and biological factors. Conversion surgery following induction immunochemotherapy is feasible in selected patients with initially unresectable disease and may improve outcome. The necessity of adjuvant immunotherapy after neoadjuvant treatment is unresolved. Clinical benefit from perioperative immunotherapy extends to PD-L1-negative and stage II disease, while its role in EGFR -mutated tumors remains uncertain. Circulating tumor DNA–based minimal residual disease assessment is emerging as a promising tool for risk stratification and treatment personalization. In parallel, novel therapeutic agents are being actively investigated in clinical trials. Conclusion Neoadjuvant or perioperative immunotherapy is emerging as a new standard of care in resectable NSCLC. Future progress will depend on refining patient selection and adapting treatment intensity using clinical and molecular biomarkers as well as new agents, to maximize cure while minimizing overtreatment.

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