ctDNA clearance predicts survival in unresectable EGFR-mutant NSCLC: a meta-analysis

Background: Circulating tumor DNA (ctDNA) is a non-invasive biomarker for monitoring non-small cell lung cancer (NSCLC). In EGFR-mutant NSCLC, ctDNA clearance during EGFR-TKI therapy is linked to improved outcomes. Methods: A systematic review was conducted following PRISMA guidelines, with data from PubMed, EMBASE, Web of Science, and Cochrane Library up to September 2025. Eligible studies were prospective cohorts or randomized trials reporting ctDNA dynamics and hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS). Results: Four studies involving a total of 336 patients met the inclusion criteria. Pooled analysis showed ctDNA clearance was significantly associated with prolonged PFS (HR = 0.34) and OS (HR = 0.29). Sensitivity analyses confirmed the robustness, and no significant publication bias was detected. Conclusions: ctDNA clearance during EGFR-TKI treatment appears to be associated with improved survival outcomes in patients with EGFR-mutant NSCLC. These findings suggest that ctDNA dynamics may serve as a promising early prognostic biomarker, although further validation in larger prospective studies and standardization of ctDNA assays, sampling time points, and clearance definitions are required.