ctDNA as a prognostic biomarker in resectable CLM: Systematic review and meta-analysis

Cell-free circulating tumor DNA (ctDNA) is synthesized by tumor cells, including metastatic tumors, and circulates in the bloodstream. Evidence suggests that ctDNA is a potential predictive and prognostic biomarker for colorectal cancer (CRC), but its predictive efficacy in detecting CRC liver metastasis (CLM) remains unclear. Additionally, its utility in the clinical setting needs further investigation. We conducted a meta-analysis to determine the utility of ctDNA as a biomarker for predicting the prognosis of CLM and investigate the relationship between CLM and ctDNA positivity. A literature search was performed in electronic databases to identify relevant studies published up to March 19, 2022. We retrieved data on overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) for both ctDNA-positive and ctDNA-negative colorectal liver metastasis (CLM) patients from the selected articles. Hazard ratios (HRs) were also calculated for these survival outcomes analysis was also performed. The stability of the combined meta-analysis was verified by sensitivity analysis and publication bias evaluation. Ten trials were included, and 615 patients were evaluated. In patients with CLM, pooled HRs revealed a substantial link between ctDNA positivity and RFS/DFS. Subgroup analysis revealed that ctDNA had a prospective detection value. Sensitivity analysis and publication bias evaluation indicated stable results. Although the results on pooled HR for OS suggested that ctDNA-positive patients had a shorter survival time, their pooled HRs had a relatively evident heterogeneity, and sensitivity analysis and publication bias evaluation indicated that pooled HRs were extremely unstable. In conclusion, our results demonstrate that ctDNA appears to be a prognostic biomarker for resectable CLM patients.