Local consolidative therapy extends survival in metastatic NSCLC with oligoresidual disease following first-line immunotherapy, irrespective of PD-L1 expression

The role of local consolidative therapy (LCT) in metastatic non-small cell lung cancer (mNSCLC) with oligoresidual disease (ORD) after first-line immunotherapy remains undefined. This study evaluated survival outcomes of LCT in this population. We retrospectively analyzed 127 mNSCLC patients lacking EGFR/ALK alterations who developed ORD (≤ 3 organs or ≤ 5 residual lesions) following first-line PD-1/PD-L1 inhibitor therapy at two centers (2019-2025). Patients received LCT (surgery/SABR/MWA/cryoablation/SABT, n = 57) or systemic therapy alone (non-LCT, n = 70). Progression-free survival (PFS) and overall survival (OS) were compared via Kaplan-Meier analysis; multivariate Cox regression identified prognostic factors. LCT significantly prolonged median PFS (14.0 vs. 7.0 months; HR = 0.171, 95% CI: 0.109-0.268; P < 0.001) and OS (27.3 vs. 15.8 months; HR = 0.049, 95% CI: 0.031-0.078; P < 0.001) versus non-LCT. Notably, survival benefits were independent of PD-L1 expression: PD-L1-high (≥ 50%) subgroup: mPFS 15.4 vs. 11.2 months (P = 0.004); mOS 32.8 vs. 22.0 months (P < 0.001). PD-L1-low (< 50%) subgroup: mPFS 14.0 vs. 7.0 months (P < 0.001); mOS 25.4 vs. 13.8 months (P < 0.001). Multivariate analysis confirmed LCT (HR ~ PFS ~ = 0.171, HR ~ OS ~ = 0.049; both P < 0.001) and high PD-L1 (HR ~ PFS ~ = 0.269, HR ~ OS ~ = 0.136; both P < 0.001) as independent protective factors. Grade 3-4 adverse events occurred in 8.8% of LCT patients (pneumothorax/radiation edema). LCT enhances survival in mNSCLC with ORD post-immunotherapy, irrespective of PD-L1 status. These findings support integrating LCT into standard care for immunotherapy-responsive ORD populations.