Circulating Tumor Cells as a Predictive Biomarker in Resectable Lung Cancer: A Systematic Review and Meta-Analysis

Background: In breast, prostate, and other epithelial tumors, circulating tumor cells (CTC) in peripheral blood may predict survival. Our study evaluated the prognostic significance of baseline and postoperative CTC in patients with early non-small cell lung cancer (NSCLC) through a meta-analytic approach. Methods: Prospective studies comparing survival outcomes between positive (CTC+) and negative CTC (CTC−) patients were systematically searched. Primary outcomes were overall (OS) and disease-free survival (DFS) with hazard ratio (HR) and 95% confidence interval (CI) as the effect measure. Pooled HR determined the prognostic role under a fixed-effect or random-effect model depending on heterogeneity. Results: Eighteen studies with 1321 patients were eligible. CTC+ patients were associated with an increased risk of death (HR 3.53, 95% CI 2.51−4.95; p < 0.00001) and relapse (HR 2.97, 95% CI 2.08−4.22; p < 0.00001). Subgroup analysis results were consistent in different subsets, including time points (baseline and postoperative) and sources (peripheral and pulmonary vein) of blood collection, detection methods (label-free, label-dependent, and RT-PCR), and follow-up duration. Conclusion: Our meta-analysis revealed that CTC is a promising predictive biomarker for stratifying survival outcomes in patients with early-stage NSCLC. However, future studies are required to validate these findings and standardize detection methods.