The role of local consolidative therapy (LCT) for metastatic cancers varies by the particular cancer type. We therefore performed a systematic review with a comparative meta-analysis of LCT versus systemic therapy alone specifically for metastatic non-small cell lung cancer (mNSCLC) Methods: Article eligibility for this PRISMA/PICOD-guided systematic review was histologic confirmation of mNSCLC, comparison of LCT (irradiation/surgery) vs. lack thereof in a randomized or propensity-matched retrospective manner, and sufficient quantitative data examining progression-free survival (PFS), overall survival (OS), and/or adverse events (AEs). Both polymetastatic and oligometastatic disease (OMD) was allowed, but not oligoprogressive/oligorecurrent disease. Statistics utilized the Mantel-Haenszel fixed-effect or random-effect model depending on the heterogeneity (I2).From 7 articles, 346 patients received LCT and 347 received systemic therapy alone. With LCT, the hazard ratio (HR) for PFS in all patients was 0.37 (95% confidence interval (CI) 0.25-0.55, p=0.01), and for OMD was 0.30 (0.24-0.38, p<0.001). For OS, the HRs were 0.53 (0.45-0.62, p<0.001) in all patients and 0.41 (0.33-0.52, p<0.001) in OMD patients. The findings remained significant when stratifying by EGFR status (HRs for PFS/OS: 0.29/0.44 for mutants and 0.31/0.39 for wild-type, respectively, p<0.001 for all) and study type (HRs for PFS/OS: 0.40/0.52 for randomized and 0.33/0.41 for retrospective, respectively, p<0.05 for all). LCT was not associated with a higher rate of grade ≥3 AEs (odds ratio 1.28, 95% CI 0.81-2.05, p=0.29).Meta-analyzing the available data shows that LCT may improve the PFS and OS of mNSCLC without increasing the risk of high-grade AEs. However, further data on polymetastatic mNSCLC are required, and these conclusions cannot be extrapolated to other (non-mNSCLC) histologies. Although many existing/ongoing trials of LCT for OMD commonly comprise mixed-histology populations, focusing on the interaction between specific tumor biology and systemic agents is required to enhance the clarity and applicability of these trials.Copyright © 2022 Elsevier Ltd. All rights reserved.