Abstract
PURPOSE: To identify the predictive role of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) for long-term outcomes in non-small cell lung cancer (NSCLC) patients. METHODS: Several databases were searched. The primary outcome was progression-free survival (PFS), and the secondary outcomes included overall survival (OS) and cancer-specific survival (CSS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined, and subgroup analyses based on the time point of MRD detection (landmark vs. longitudinal) and treatment (surgery vs. chemoradiotherapy) were further performed. RESULTS: Ten studies with 1859 cases were included. Pooled results demonstrated that positive ctDNA MRD significantly predicted worse PFS (HR = 11.19, 95% CI: 6.10-20.52, P < 0.001), OS (HR = 6.34, 95% CI: 2.27-17.74, P < 0.001) and CSS (HR = 16.67, 95% CI: 10.00-25.00, P < 0.001). Subgroup analysis by the time points of MRD detection (landmark: HR = 8.93, P < 0.001; longitudinal: HR = 17.52, P < 0.001) and treatment (surgery: HR = 11.63, P < 0.001; chemoradiotherapy: HR = 5.56, P < 0.001) revealed consistent results. CONCLUSION: ctDNA-based MRD could serve as a valuable prognostic indicator in NSCLC, and patients with positive ctDNA-based MRD are at significantly greater risk of recurrence and lower survival.