Neoadjuvant nonablative stereotactic body radiotherapy plus immunotherapy yields similar pathologic response as chemoimmunotherapy in non-small cell lung cancer.

[OBJECTIVE] Neoadjuvant chemoimmunotherapy is currently the standard of care for clinical stages IB (≥4 cm) to IIIB (N2) non-small cell lung cancer without EGFR or ALK alterations. We previously reported results from a phase II trial comparing neoadjuvant immunotherapy alone with nonablative stereotactic body radiotherapy plus immunotherapy. In this article, we compare the oncological outcomes associated with stereotactic body radiotherapy plus immunotherapy with those after chemoimmunotherapy in surgically resected patients.

[METHODS] We retrospectively reviewed our institutional database to identify patients with non-small cell lung cancer who received neoadjuvant chemoimmunotherapy or stereotactic body radiotherapy plus immunotherapy followed by resection. The primary end point was major pathologic response. Secondary end points were pathologic complete response, nodal downstaging, postoperative adverse events, 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.

[RESULTS] Sixty-five patients were identified between January 2017 and December 2024; 39 patients received chemoimmunotherapy, and 26 patients received stereotactic body radiotherapy plus immunotherapy. Baseline characteristics were largely similar. Major pathologic response occurred in 51.3% of patients receiving chemoimmunotherapy and 61.5% of patients receiving stereotactic body radiotherapy plus immunotherapy (P = .67). Pathologic complete response occurred in 30.8% of each group (P = 1.0). Nodal downstaging (cN1/N2 to pN0) rates were 71.4% (20/28) after chemoimmunotherapy and 68.8% (11/16) after stereotactic body radiotherapy plus immunotherapy. Postoperative adverse events were similar. There was no 90-day mortality. Median follow-up was 14.7 months after chemoimmunotherapy and 66.5 months after stereotactic body radiotherapy plus immunotherapy. Although overall survival was similar, recurrence-free survival was improved with stereotactic body radiotherapy plus immunotherapy (2-year recurrence-free survival: chemoimmunotherapy 64.4% vs stereotactic body radiotherapy plus immunotherapy 83.3%, P = .01).

[CONCLUSIONS] In this single-institution retrospective study, neoadjuvant chemoimmunotherapy and stereotactic body radiotherapy plus immunotherapy were associated with similar depths of pathologic response, nodal downstaging, postoperative adverse events, and overall survival. Stereotactic body radiotherapy plus immunotherapy was associated with a significant improvement in recurrence-free survival.