Abstract
PURPOSE: Lung cancer remains the leading cause of cancer-related mortality worldwide, with a substantial risk of recurrence even in early-stage non-small cell lung cancer (NSCLC) after curative surgery. Circulating tumor DNA (ctDNA)-based detection of minimal residual disease (MRD) has emerged as a promising tool for identifying patients at increased risk of relapse. However, the predictive effectiveness of ctDNA remains uncertain because of variability in study designs, detection strategies, and statistical power. MATERIALS AND METHODS: We conducted a systematic meta-analysis of 30 studies involving 3,287 patients with postoperative NSCLC to evaluate the diagnostic performance of ctDNA-based MRD testing for recurrence detection and survival prediction. Eligible studies were identified through a comprehensive literature search and quality-assessed using the QUADAS-2 tool. Pooled diagnostic estimates were calculated using bivariate random-effects models. Subgroup analyses compared tumor-informed and tumor-agnostic detection strategies at both landmark and longitudinal postoperative time points. RESULTS: In landmark analyses, tumor-informed assays demonstrated higher specificity (0.97 v 0.93) and AUC (0.81 v 0.70) than tumor-agnostic approaches, which showed slightly higher sensitivity (0.44 v 0.42). In longitudinal monitoring, the differences narrowed: tumor-informed assays retained higher specificity (0.96 v 0.88), whereas tumor-agnostic methods exhibited modestly higher sensitivity (0.79 v 0.76) and AUC (0.91 v 0.86). CONCLUSION: Our findings indicate that ctDNA-based MRD testing provides clinically meaningful prognostic information for postoperative recurrence in early-stage NSCLC. Both detection strategies offer complementary strengths, with tumor-informed assays excelling in specificity and tumor-agnostic approaches offering greater sensitivity in some settings. These results highlight the potential of ctDNA MRD testing to enhance postoperative surveillance and guide personalized disease management in early-stage NSCLC.