Circulating tumour DNA in patients with stage III colon cancer: multicentre prospective PROVENC3 study
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Publication date
2026-01
Authors
Alarcón, Carmen Rubio
Georgiadis, Andrew
Franken, Ingrid
Wang, Haoyue
van Nassau, Sietske C M W
Schraa, Suzanna J.
van der Kruijssen, Dave E W
van Rooijen, K L
Linders, Theodora C
Delis-van Diemen, Pien
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Abstract
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.
Keywords
Aged, Aged, 80 and over, Biomarkers, Tumor/blood, Chemotherapy, Adjuvant, Circulating Tumor DNA/blood, Colonic Neoplasms/pathology, Female, Humans, Male, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Neoplasm, Residual, Prognosis, Prospective Studies, Journal Article, Multicenter Study
Citation
Rubio-Alarcón, C, Georgiadis, A, Franken, I A, Wang, H, van Nassau, S C M W, Schraa, S J, van der Kruijssen, D E W, van Rooijen, K, Linders, T C, Delis-van Diemen, P, Alkemade, M, Bolijn, A, Tijssen, M, Lemmens, M, Meiqari, L, Ketelaars, S L C, Closa-Mosquera, A, van Dongen, M M W, Lanfermeijer, M, Lissenberg-Witte, B I, Bosch, L J W, Bisschop-Snetselaar, T, Adriaans, B C, Greer, A, Riley, D, White, J R, Greco, C, Cox, L, Fox, J, Victor, K, Leech, C, Angiuoli, S V, Kok, N F M, Punt, C J A, van den Broek, D, Koopman, M, Meijer, G A, Velculescu, V E, Roodhart, J M L, Coupé, V M H, Sausen, M, Vink, G R, Fijneman, R J A & Other Members of the PLCRC-MEDOCC Group 2026, 'Circulating tumour DNA in patients with stage III colon cancer : multicentre prospective PROVENC3 study', The British journal of surgery, vol. 113, no. 1, znaf281. https://doi.org/10.1093/bjs/znaf281