Neoadjuvant Non-Ablative SBRT Plus Immunotherapy Yields Similar Pathologic Response as Chemo-Immunotherapy in Non-Small Cell Lung Cancer

Neoadjuvant chemoimmunotherapy (Chemo-IO) is currently the standard of care for clinical stages IB(≥4cm)-IIIB(N2) NSCLC without EGFR or ALK alterations. We previously reported results from a phase II trial comparing neoadjuvant immunotherapy alone with non-ablative SBRT plus immunotherapy (SBRT-IO). Here we compare oncological outcomes associated with SBRT-IO to those after Chemo-IO in surgically resected patients. We retrospectively reviewed our institutional database to identify patients with NSCLC who received neoadjuvant Chemo-IO or SBRT-IO followed by resection. The primary endpoint was MPR. Secondary endpoints were pCR, nodal downstaging, postoperative AEs, and survival. Intergroup differences in pathologic response were compared by contingency analysis. Survival was assessed by the log-rank test and Cox proportional hazards model. Sixty-five patients were identified between 1/2017-12/2024; 39 received Chemo-IO and 26 SBRT-IO. Baseline characteristics were largely similar. MPR occurred in 51.3% of Chemo-IO patients and 61.5% of SBRT-IO patients (p=0.67). pCR occurred in 30.8% of each group (p=1.0). Nodal down-staging (cN1/N2 to pN0) rates were 71.4% (20/28) after Chemo-IO and 68.8% (11/16) after SBRT-IO. Postoperative AEs were similar. There was no 90-day mortality. Median follow-up was 14.7 months after Chemo-IO and 66.5 months after SBRT-IO. Though overall survival was similar, recurrence-free survival (RFS) was improved with SBRT-IO (2-year RFS: Chemo-IO 64.4% vs SBRT-IO 83.3%, p=0.01). In this single-institution retrospective study, neoadjuvant Chemo-IO and SBRT-IO were associated with similar depths of pathologic response, nodal down-staging, postoperative AEs, and overall survival. SBRT-IO was associated with a significant improvement in RFS.