Prognostic impact of ctDNA in patients with colorectal cancer and liver metastases: Associations with progression-free and overall survival.

Abstract

141 Background: Circulating tumor DNA (ctDNA) has the potential to serve as a biomarker for disease monitoring in metastatic colorectal cancer. However, the prognostic value of ctDNA in patients with liver metastases (LM) remains to be fully elucidated. This study evaluates the impact of ctDNA on recurrence-free survival (RFS) and overall survival (OS) in patients with LM. Methods: A systematic literature review was conducted with PubMed, analyzing 60 articles and including 16 unique studies. These were patients with metastatic colorectal cancer with liver metastases who underwent ctDNA testing at multiple disease time points before and after surgery. All patients underwent curative intent surgery and were R0 subsequently. Patients were stratified by ctDNA levels (positive vs negative during treatment). RFS and OS were compared between groups using R software. A random effect model was utilized. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Results: These nineteen studies included 2,641 patients. Overall, ctDNA positivity was associated with statistically worse RFS and OS. The pooled hazard ratio (HR) for RFS was 4.79 (95% CI, 3.57–6.42; 100%), indicating a more than fourfold increased risk of recurrence in ctDNA-positive patients. Heterogeneity across studies was moderate (I² = 56.5%, τ² = 0.1654, p<0.001), suggesting some variability in effect size. Analysis of OS demonstrated a significant association between ctDNA positivity and worse survival outcomes. The pooled HR was 3.08 (95% CI, 2.06–4.60) 100%. Heterogeneity was moderate (I² = 62.1%, τ² = 0.2654, p<0.001). Conclusion: In patients with colorectal cancer and liver metastases, ctDNA positivity is associated with a statistically significant decrease in RFS and OS. These findings support the role of ctDNA as a dynamic biomarker for risk stratification and treatment monitoring in this high-risk population. Pooled hazard ratios (HR) with 95% confidence intervals (CI) for recurrence-free survival, overall survival, and progression-free survival using a random-effects model. Random Effects Model Hazard Ratio (HR) 95% CI Weight (%) I² (p-value) Recurrence Free Survival 4.79 [3.57; 6.42] 100% I² = 56.5%, p < 0.001 Overall Survival 3.08 [2.06; 4.60] 100% 62.1% (p < 0.001) Weights reflect the relative contribution of each study to the meta-analysis. Heterogeneity across studies was assessed using the I² statistic with corresponding p-values.