Neoadjuvant chemoimmunotherapy in resected stage III non-small-cell lung cancer: real-world data from a nationwide registry

Background: Neoadjuvant chemoimmunotherapy is increasingly used in resectable stage III non-small-cell lung cancer. The objective was to compare oncological effectiveness, surgical complexity and perioperative safety of neoadjuvant chemoimmunotherapy compared to chemotherapy.

Methods: A multicentre cohort study was performed within the Registry of the Spanish Society of Thoracic Surgery. Consecutive patients with stage III non-small-cell lung cancer treated with chemoimmunotherapy or chemotherapy followed by anatomical resection (January 2023–April 2025) were analysed (114 patients: chemoimmunotherapy 77; chemotherapy 37). Oncological variables were pathological complete response, downstaging and complete resection (International Association for the Study of Lung Cancer criteria). Surgical and perioperative outcomes were compared, including complications and mortality. Propensity-score matching was used to reduce confounding and outcomes were compared using paired tests.

Results: After matching, 68 patients remained (34 pairs). Chemoimmunotherapy yielded higher pathological complete response [38% vs. 12%; relative risk (RR) 3.3, 95% confidence interval (CI): 1.2–9.0; P=0.02], downstaging (79% vs. 56%; RR 1.4, 95% CI: 1.0–2.0; P=0.057) and complete resection (74% vs. 41%; RR 1.8, 95% CI: 1.1–3.1; P=0.049). Median operative time was longer (240 vs. 180 minutes; P=0.048). Overall postoperative complications were higher (41% vs. 21%; RR 2.0, 95% CI: 0.9–4.3; P=0.12), whereas major morbidity, reoperations and in-hospital, 30-day and 90-day mortality were low and comparable.

Conclusions: Neoadjuvant chemoimmunotherapy for resected stage III non-small-cell lung cancer improved pathological complete response, downstaging and complete resection versus chemotherapy, at the expense of longer operations and higher morbidity, without an increase in severe complications or early mortality.