2025/12/10 by Carmen Rubio-Alarcón, Andrew Georgiadis, Ingrid A. Franken +71 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Cancer Genomics and Diagnostics #Cancer Cells and Metastasis #Genetic factors in colorectal cancer
paper · doi:10.1093/bjs/znaf281
openalex publication_date 2025/12/10 · openalex created_date 2026/01/11 · openalex updated_date 2026/07/22
BACKGROUND: Circulating tumour DNA (ctDNA) is a promising biomarker to guide clinical decision-making. The aim of this study was to investigate the prognostic value of postoperative ctDNA in patients with stage III colon cancer who received adjuvant chemotherapy (ACT). METHODS: PROVENC3 was a multicentre prospective study of patients who underwent resection of pathological stage III colon cancer. Blood samples were collected at a median of 13 (interquartile range 4-20) days after resection. The presence of minimal residual disease was determined using Labcorp® Plasma Detect™, a novel tumour-informed whole genome sequencing (WGS) ctDNA test. The primary endpoint was 3-year time to recurrence (TTR). ctDNA status was further combined with pathological risk status to investigate the combined prognostic value. RESULTS: The median follow-up of the 209 patients who were included was 40 months. In total, 28 patients (13%) had detectable ctDNA after surgery. Postoperative ctDNA-positive patients had a worse TTR compared with ctDNA-negative patients (HR 6.2 (95% c.i. 3.4 to 11.2); P < 0.001). Of all ctDNA-positive patients, 36% did not develop recurrences during 3-year follow-up. Detectable ctDNA after ACT was associated with worse TTR (HR 7.9 (95% c.i. 3.9 to 15.9); P < 0.001). ctDNA status combined with pathological risk classification resulted in a 3-year recurrence risk that varied from 82% for pathological high-risk (pT4/N2) ctDNA-positive patients to 7% for pathological low-risk (pT1-3 N1) ctDNA-negative patients (HR 28.5 (95% c.i. 10.5 to 77.2); P < 0.001). CONCLUSION: Postoperative ctDNA detection using a tumour-informed WGS test improves prognosis stratification in stage III colon cancer and may help to personalize adjuvant treatment.