Neoadjuvant and perioperative chemo-immunotherapy in early-stage non-small cell lung cancer: international expert...

Integration of immune checkpoint inhibitors with perioperative chemotherapy has significantly improved pathological response rates and survival outcomes in patients with resectable NSCLC. In this context, an international expert panel convened to discuss optimal use of neoadjuvant and perioperative chemo-immunotherapy in individuals with early-stage/locally advanced resectable NSCLC, based on emerging trial data.

A virtual expert panel meeting was held on July 10, 2025 under the auspices of the Italian Association of Thoracic Oncology (AIOT). Seven thoracic oncology experts reviewed current evidence from pivotal trials. The panel addressed predefined clinical questions spanning pre-treatment evaluation, choice of neoadjuvant vs perioperative strategies, and patient selection. Shared-opinion statements were developed through moderated discussion.

The panel endorsed pathological mediastinal staging and molecular testing in all candidates before therapy. Neoadjuvant and perioperative chemo-immunotherapy were considered a new standard for resectable stage II-III NSCLC after thorough and thoughtful multidisciplinary board discussion, having shown improved pathological complete response (pCR), event-free survival (EFS), and overall survival (OS), and was deemed overall safe without compromising surgery. PD-L1-negative tumors were not excluded from immunotherapy benefit, although magnitude of benefit was lower. The panel recommended neoadjuvant or perioperative approaches especially for resectable stage III and N-positive disease, whereas upfront surgery could be considered for selected stage II N0 cases. No evidence currently favors perioperative over neoadjuvant strategy in efficacy, or viceversa. The panel emphasized that regimen choice should consider trial eligibility criteria, local drug approvals, and patient factors. High-priority research areas identified included trials comparing neoadjuvant vs perioperative strategies, studies of biomarker-driven therapy personalization, and novel combination approaches to further improve outcomes.

Chemo-immunotherapy is an essential component of therapy for subjects with operable and resectable NSCLC. Based on current evidence, the expert panel formulated guideline recommendations for clinical practice. These expert statements aim to guide clinicians in integrating emerging perioperative immunotherapy regimens while awaiting further data from clinical trials.