Perioperative Outcomes and Pathological Response After Neoadjuvant Nivolumab Plus Platinum Chemotherapy in Clinically Node-Negative Non-Small Cell Lung Cancer.

PURPOSE: The role of neoadjuvant chemoimmunotherapy in clinically node-negative (cN0) non-small cell lung cancer (NSCLC) remains unclear. This study aimed to evaluate perioperative outcomes and pathological response in patients with cN0. METHODS: This was a pre-specified secondary analysis of the CReGYT-04 Neo-Venus registry, a nationwide multicenter retrospective study in Japan. A total of 129 patients with stage IIA-IIIB NSCLC who received neoadjuvant nivolumab plus platinum-doublet chemotherapy were included. Patients were stratified by clinical nodal status (cN0 vs. cN1-2), and clinical characteristics, perioperative outcomes, and pathological responses were compared. RESULTS: The analysis included 31 patients with cN0 and 98 with cN1-2. Preoperative treatment discontinuation was more frequent in the cN0 group (22.6% vs. 9.2%), primarily due to immune-related adverse events (irAEs) or disease progression. The surgical cancellation rate was 6.5% in the cN0 group and 9.2% in the cN1-2 group. Postoperative outcomes, including complication rates and hospital stay, were comparable between the groups, with no 30-day mortality observed in the cN0 group. Pathological complete response was achieved in 34.5% of the cN0 group and 36.1% of the cN1-2 group; major pathological response was observed in 48.3% and 62.7%, respectively. R0 resection was achieved in all cN0 patients. CONCLUSIONS: In patients with resectable cN0 NSCLC, nivolumab-based neoadjuvant chemoimmunotherapy was associated with perioperative outcomes and pCR rates similar to those observed in patients with cN1-2. These findings suggest that this regimen may represent a treatment option for patients with cN0, with careful attention to irAEs and disease progression.