Real-world outcomes of unresected non-small cell lung cancer following neoadjuvant chemoimmunotherapy

OBJECTIVE: Although neoadjuvant chemoimmunotherapy is promising for resectable stage II-III non-small cell lung cancer (NSCLC), some patients do not proceed to surgery. We aimed to investigate the clinical course and outcomes of patients whose surgery was cancelled after neoadjuvant chemoimmunotherapy. METHODS: This retrospective multicentre study (CReGYT-04: Neo-Venus study) included patients with resectable clinical stage II-III NSCLC who received nivolumab neoadjuvant chemotherapy (2023-2024). Clinical characteristics were compared between a surgery-cancelled group and surgery-performed group. In the surgery-cancelled group, the reasons for surgery cancellation, salvage treatments, and effects of immune-related adverse events (irAEs) were evaluated. RESULTS: Among 126 patients, 11 (8.7%) did not undergo surgery. Compared with the surgery-performed group, the surgery-cancelled group had a heavier smoking history, a higher frequency of adjacent organ invasion, a greater proportion of squamous cell carcinoma histology, and more frequent Grade 3-4 irAEs. Reasons for cancelling surgery included disease progression (n = 6, 55%), patient refusal (n = 3, 27%), and irAEs (n = 2, 18%). Four (36%) patients received intensive salvage treatment (concurrent chemoradiotherapy, 3 patients; chemoimmunotherapy, 1 patient), whereas seven patients received best supportive care (n = 4) or less-intensive salvage treatment such as radiotherapy alone (n = 2) and docetaxel monotherapy (n = 1). Among the four patients in the surgery-cancelled group who developed Grade 3-4 irAEs, none received intensive salvage treatment. CONCLUSIONS: Intensive salvage treatment was administered to 36% of patients whose surgery was cancelled after neoadjuvant chemoimmunotherapy. These findings highlight the importance of optimising patient selection and irAE management to preserve opportunities for curative-intent treatment when adopting neoadjuvant strategies.