Concerned issues and controversies in perioperative immunotherapy for resectable non-small cell lung cancer

Lung cancer is the most prevalent malignant tumor in China, with the highest incidence and mortality rates. Among the various types of lung cancer, non-small cell lung cancer (NSCLC) accounts for approximately 80% to 85%. Radical surgery is the primary treatment for early-stage NSCLC; however, postoperative recurrence remains a significant clinical challenge. The incorporation of perioperative chemotherapy with surgery has yielded only a modest improvement in the 5-year survival rate, approximately 5%, thereby highlighting the urgent need for more effective systemic treatment alternatives. In recent years, immunotherapeutic drugs, represented by programmed death receptor 1/programmed death ligand 1 (PD-1/PD-L1) monoclonal antibodies, have gradually advanced from later-line therapy to front-line treatment for NSCLC, and have now brought breakthrough progress to perioperative treatment. Multiple phase III immunotherapy clinical trials have demonstrated that both neoadjuvant and adjuvant immunotherapies can significantly enhance the pathological response rate, event-free survival (EFS), and disease-free survival (DFS) in patients with stage II to III NSCLC. Such findings have established new treatment standards aimed at reducing recurrence rates and extending overall survival (OS). Additionally, the potential benefits of the "neoadjuvant plus adjuvant" immunotherapy model have been validated, significantly decreasing the risk of postoperative recurrence in specific patient populations. Future research will continue to explore the efficacy of immunotherapy across different subgroups to maximize clinical benefits while minimizing treatment-related toxicity. Nevertheless, the perioperative application of immunotherapy is accompanied by significant concerns and controversies. This review primarily outlines the latest advancements in perioperative immunotherapy and explores some doubts and controversies encountered in clinical practice, aiming to provide strategies and insights for managing and treating NSCLC in the perioperative setting.