ETD

• colorectal cancer
• liquid biopsy
• liver limited disease

Background: Metastatic colorectal cancer (mCRC) can present as a liver-limited disease (LLD) in 20-30% of patients. Radical resection or ablation of liver metastases significantly improves survival, but disease recurrence remains common, occurring within six months after surgery in 35-45% of cases. Post-surgical circulating tumor DNA (ctDNA) is a well-established prognostic biomarker for minimal residual disease (MRD). However, the prognostic impact of pre-operative ctDNA following upfront systemic treatment for initially unresectable disease remains unexplored. This study aimed to evaluate the prognostic value of pre-surgical ctDNA and its dynamics in this setting.
Materials and methods: Serial plasma samples from 116 patients were collected at baseline (pre-chemotherapy), pre-surgery, and post-surgery. Analysis was performed using a tumor-naïve MRD test assay combining both genomic and methylomic assays.
Results: A ≥50% reduction in ctDNA variant allele fraction (VAF) from baseline to pre-surgery was independently associated with improved RFS (median RFS: 18.8 vs. 9.8 months; HR: 2.21; p=0.012), confirmed at the multivariate analysis (p = 0.022). Post-surgery ctDNA positivity was confirmed as a strong predictor of recurrence (HR: 6.66; p<0.001).
Conclusions: Tracking pre-surgical ctDNA dynamics provides prognostic information on post-surgery recurrence risk in initially unresectable LLD mCRC, potentially informing tailored patient management.