Detection of Circulating Tumor DNA Correlates with Recurrence and Survival in Localized Non-Small-Cell Lung Cancer: A Meta-Analysis

Abstract

Circulating tumor DNA (ctDNA) is approved recently to use in clinical practice of solid tumor. Several large-scale prospective studies also revealed that minimal residual disease based on ctDNA (ctDNA-MRD) is a potential predictive and prognostic biomarker of localized non-small-cell lung cancer (NSCLC) receiving curative treatment (surgery or radiotherapy). However, there are still barriers to clinical management of ctDNA/ctDNA-MRD in localized NSCLC, and the most significant is effectiveness and detection times of ctDNA/ctDNA-MRD. This meta-analysis aims to clarify the prognostic value of the ctDNA and ctDNA-MRD in predicting the disease recurrence and survival of localized NSCLC. Electronic databases (Pubmed/MEDLINE, Web of Science, Cochrane Library, meeting abstracts) were comprehensively searched for eligible studies from January 2001 to January 2023. The Hazard ratio (HR) from relevant reports was extracted to better evaluate the correlation of ctDNA and ctDNA-MRD detected in plasma with clinical outcomes among patients with localized NSCLC. Pooled results including ctDNA detection rate, disease-/relapse-/progression- free survival (DFS/RFS/PFS) and overall survival (OS) were obtained and analyzed by Review Manager 5.4.1. A total of 18 eligible studies with 2692 patients were enrolled in the final analysis. The pooled analysis revealed that ctDNA detection in pretreatment plasma indicated poor prognosis for DFS/RFS/PFS (HR 3.82, 95% CI 2.85 - 5.12, p < .00001; Figure 1) with a long-term effect on OS (HR 4.88, 95% CI 3.29 - 7.24, p < .00001; Figure 2). The same result was also observed in patients with positive posttreatment ctDNA-MRD who have shorter DFS/RFS/PFS (HR 7.15, 95% CI 5.50 - 9.31, p < .00001; Figure 3) and OS (HR 4.34, 95% CI: 2.51-7.51, p < .00001; Figure 4) compared to negative groups. Based on the results from our meta-analysis, the presence of pretreatment ctDNA or posttreatment ctDNA-MRD in radically treated localized NSCLC is associated with higher risk of recurrence and poorer survival. This finding is supportive of ctDNA/ctDNA-MRD becoming a widespread prognostic biomarker in localized NSCLC.