Surgical and Pathological Outcomes of Non-Small-Cell Lung Cancer Patients Who Did Not Radiologically Respond to Neoadjuvant Chemo-Immunotherapy

Background: Neoadjuvant chemo-immunotherapy is now a standard treatment for resectable non-small cell lung cancer (NSCLC) patients with clinical stage II–III disease. However, some patients do not respond to the treatment radiologically, and the surgical and pathological outcomes in such patients remain unclear. Methods: We conducted a multi-institutional retrospective analysis of patients who received neoadjuvant chemo-immunotherapy at 29 centers in Japan (CReGYT-04 Neo-Venus study). In this study, we focused specifically on radiological non-responders to neoadjuvant chemoimmunotherapy. Results: Of 124 eligible patients, radiological responses indicated a complete/partial response (CR/PR) in 84, stable disease (SD) in 35, and progressive disease (PD) in 5 patients. Nine patients (five with PD, two with SD, and two with PR) did not undergo surgical resection, and one SD patient had exploratory thoracotomy. Surgical outcomes, including minimally invasive approach rates, procedures, operation time, blood loss, and postoperative complications, were similar between patients with SD and those with CR/PR. Among 31 SD patients with available pathological data, a major pathologic response (MPR) was achieved in 26%, and pre-treatment PD-L1 status (p<0.01) and a ≥50% decrease in the maximum standardized uptake value on FDG-PET/CT (p=0.03) were associated with MPR. Conclusions: Surgical outcomes were similar between the SD and CR/PR groups, and 26% of SD patients achieved MPR, supporting strategies that actively pursue surgical resection, even in radiological non-responders to neoadjuvant treatment.