Postsurgical ctDNA is Associated With Recurrence in Metastatic Colorectal Cancer

Clinical Summary:

• Design/Population: In this prospective study, researchers evaluated ctDNA dynamics in 116 patients with initially unresectable liver-limited metastatic colorectal cancer who underwent liver resection after upfront chemotherapy.
• Key Outcomes: Postsurgical ctDNA positivity strongly predicted recurrence, while reductions in ctDNA levels before surgery were associated with improved relapse-free survival.
• Clinical Relevance: ctDNA dynamics may help risk-stratify patients and inform individualized treatment strategies. 

Results from a prospective study suggest that circulating tumor DNA (ctDNA) dynamics may help stratify recurrence risk among patients with liver-limited metastatic colorectal cancer (mCRC) undergoing liver resection after upfront chemotherapy. 

“Resection of liver metastases improves survival in patients with [mCRC) with liver-limited disease, but relapse remains common,” stated Roberto Moretto, MD, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy, and coauthors. “Postresection [ctDNA) is a valid prognostic biomarker… however, no data are available regarding the prognostic effect of pre-surgery ctDNA after upfront chemotherapy.”

In this study, researchers evaluated ctDNA dynamics in 116 patients with initially unresectable liver-limited mCRC who underwent liver resection after upfront chemotherapy. Samples collected at baseline, before resection, and after resection were analyzed using a tumor-naïve minimal residual disease (MRD) assay. The primary end point was relapse-free survival (RFS). A key secondary end point was overall survival (OS). 

At analysis, median RFS was 10.34 months in ctDNA-positive patients and 12.26 months in ctDNA-negative patients (hazard ratio [HR], 1.22; 95% confidence interval [CI], 0.77 to 1.92; P = .39). The 24-month OS rates were 95.8% and 77.7%, respectively (HR, 6.11; 95% CI, 1.65 to 22.6; P = .007). Exploratory results showed that median RFS was 21 months in patients with a ≥50% reduction in variant allele frequency from baseline to pre-surgery and 9.8 months in patients without substantial ctDNA decline (P = .014), and this association remained significant in multivariate analysis (P = .022). Median RFS was not reached in patients who were ctDNA-negative following resection and 5.52 months in patients who were ctDNA-positive following resection (HR, 6.66; 95% CI, 3.31 to 13.39; P < .001), with 100% specificity and 56.4% sensitivity. 

ctDNA dynamics from both prior to and following resection further refined risk stratification, independent of adjuvant chemotherapy use. Quantitative ctDNA measures also correlated with RFS.

“ctDNA dynamics provide independent prognostic information in patients with [liver-limited] mCRC candidate to resection of liver metastases after first-line systemic therapy,” concluded Dr Moretto et al. “These findings highlight that the longitudinal quantitative ctDNA assessment is a promising and minimally invasive strategy to refine patient selection amenable to secondary surgery in a setting with currently unreliable prognostic markers.”

Source:

Moretto R, Studiale V, Hyun SW, et al. Circulating tumor DNA dynamics in patients with liver-limited metastatic colorectal cancer resected after first-line systemic treatment. Clin Cancer Res. Published online: May 18, 2026. doi: 10.1158/1078-0432.ccr-25-4641