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 chemo-immunotherapy. 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. In the analysis of residual tumor classification, R0 resection was achieved in 88% of patients in the SD group and 98% of those in the CR/PR group. Accordingly, the odds of R1/R2 resection were higher in the SD group than in the CR/PR group (OR, 5.6; 95% CI, 0.8–65.3; p = 0.051). Among 31 SD patients with available pathological data, a major pathologic response (MPR) was achieved in 26%; in an exploratory analysis, pre-treatment PD-L1 status (p < 0.01) and a >50% decrease in the maximum standardized uptake value (SUVmax ratio < 50%) on FDG-PET/CT (p = 0.03) were associated with MPR. Conclusions: No statistically significant differences in surgical outcomes, including adverse events, were observed between the SD and CR/PR groups, while the odds of R1/R2 resection were higher in the SD group. Despite the absence of a radiological response, 26% of SD patients achieved MPR, highlighting the limitations of current image-based assessments in evaluating the efficacy of induction chemo-immunotherapy.