3613 - Beyond the Oligometastatic Paradigm: Survival Trends with SBRT In High-Burden Extracranial Metastatic NSCLC

Purpose/Objective(s): Survival in metastatic non–small cell lung cancer (mNSCLC) remains poor despite the immunotherapy era. Prior phase II trials of stereotactic body radiotherapy (SBRT) in the oligoprogressive setting demonstrated improved outcomes with standard-of-care therapy. We evaluated whether SBRT to symptomatic extracranial metastases is associated with survival benefit across metastatic-burden thresholds beyond the traditional oligometastatic definition (=5 lesions).

Materials/Methods: We retrospectively analyzed 130 patients with mNSCLC treated in a multicenter single-institution cohort with systemic therapy alone (n=65) or systemic therapy plus SBRT to symptomatic extracranial metastases (n=65). Metastatic burden was quantified by combined bone and visceral metastasis counts and stratified as =5 versus >5 lesions. Additional variables included systemic therapy class (immunotherapy or targeted therapy), timing of radiation, and survival outcomes. Overall survival (OS) was estimated using Kaplan–Meier methods and compared with log-rank testing. Multivariable Cox proportional hazards models adjusted for treatment arm and total metastatic burden. A 90-day landmark analysis mitigated immortal-time bias.

Results:

Median OS was longer with SBRT (35.0 vs 13.6 months). Twelve- and 24-month OS rates favored SBRT (78.1% and 67.2%) versus systemic therapy alone (54.0% and 42.7%), though this did not reach statistical significance (log-rank p=0.25). On Cox analysis, SBRT was associated with a nonsignificant reduction in mortality (HR 0.78; p=0.25). Across metastatic-burden strata, OS curves consistently favored SBRT, including among patients with >5 lesions. Among patients with =5 metastases, deaths occurred in 29 (70.7%) vs 26 (60.5%) (HR 0.86; p=0.57). In those with >5 metastases, deaths occurred in 15 (65.2%) vs 16 (80.0%), with longer median OS in the SBRT arm (HR 0.67; p=0.27). After multivariable adjustment, SBRT remained associated with reduced mortality (HR 0.75, 95% CI 0.48–1.16; p=0.197).

SBRT demonstrated numerically improved OS among patients with bone metastases (69.0% vs 64.3%; HR 0.67; p=0.33), while outcomes in visceral metastases were comparable (12-/24-month OS: 73%/61% vs 52%/41%; p=0.31) both without statistical significance. In the 90-day landmark analysis, the survival difference was attenuated (HR 0.85, 95% CI 0.55–1.32; p=0.473), suggesting partial early survival selection.

Conclusion: In mNSCLC, SBRT to symptomatic extracranial metastases was associated with numerically prolonged OS across metastatic-burden strata, including patients with higher-volume disease. However, statistical significance was not maintained after adjustment for total burden, and the effect was attenuated in landmark analysis. These findings suggest a potential survival signal beyond traditional oligometastatic thresholds, warranting Prospective phase II studies to refine metastatic-burden and revised symptom criteria for patient selection.