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

SIMPLE SUMMARY: Lung cancer is the most common cause of cancer-related deaths worldwide. Circulating tumor cells (CTC) are cancer cells that are disseminated in the bloodstream and may be responsible for early recurrence and poor rates of survival. We conducted a systematic review and meta-analysis of 18 prospective studies comprising 1321 patients that reported CTC in resectable non-small cell lung cancer. Our analysis revealed that the presence of CTC in both the baseline and postoperative period was associated with an increased risk of recurrence and death compared to an absence of CTC in lung cancer patients. The results were independent of sources of CTC (peripheral, pulmonary vein), detection methods, and follow-up duration. CTCs hold a significant prognostic and predictive potential, as evident in our meta-analysis; however, heterogeneity of data, publication bias, and variable cut-off values limit its clinical utility. ABSTRACT: 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.