Perioperative Immunotherapy for Node-Negative Non-Small Cell Lung Cancer-Current Evidence and Future Directions

Neoadjuvant immunotherapy has gone from an idea to an indication in locally advanced lung cancer. Several phase III trials have demonstrated the superiority of neoadjuvant chemoimmunotherapy compared with chemotherapy in this setting. Although such progress has revolutionized the treatment of locally advanced disease, the unmet needs of stage I and stage II patients without lymph node disease have largely been underrepresented in existing trials. Up-front resection with few patients going on to complete adjuvant therapy remains the norm for most stage I and II patients. Emerging evidence now supports the exploration of supplemental checkpoint blockade in well-selected early-stage, node-negative patients with large tumors and no actionable driver mutations. Although concerns surrounding safety and risk exist, patient selection could be substantially improved using novel biomarker approaches that leverage our understanding of the tumor immune microenvironment of lung cancer. This review provides a comprehensive overview of the opportunities and controversies of perioperative immunotherapy in node-negative lung cancer.