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Circulating tumour DNA in patients with stage III colon cancer: multicentre prospective PROVENC3 study.

Carmen Rubio-Alarcón ,
Andrew Georgiadis ,
Ingrid A Franken ,
Haoyue Wang ,
Sietske C M W van Nassau ,
Suzanna J Schraa ,
Dave E W van der Kruijssen ,
Karlijn van Rooijen ,
Theodora C Linders ,
Pien Delis-van Diemen ,
Maartje Alkemade ,
Anne Bolijn ,
Marianne Tijssen ,
Margriet Lemmens ,
Lana Meiqari ,
Steven L C Ketelaars ,
Adria Closa-Mosquera ,
Miranda M W van Dongen ,
Mirthe Lanfermeijer ,
Birgit I Lissenberg-Witte ,
Linda J W Bosch ,
Teunise Bisschop-Snetselaar ,
Bregje C Adriaans ,
Amy Greer ,
David Riley ,
James R White ,
Christopher Greco ,
Liam Cox ,
Jesse Fox ,
Kaitlin Victor ,
Catherine Leech ,
Samuel V Angiuoli ,
Niels F M Kok ,
Cornelis J A Punt ,
Daan van den Broek ,
Miriam Koopman ,
Gerrit A Meijer ,
Victor E Velculescu ,
Jeanine M L Roodhart ,
Veerle M H Coupé ,
Mark Sausen ,
Geraldine R Vink ,
Remond J A Fijneman ,

Abstract

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.

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.

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).

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).

More about this publication

The British journal of surgery

Volume 113
Issue nr. 1
Publication date 24-12-2025

Full text links

Publisher website (DOI) 10.1093/bjs/znaf281
Europe PubMed Central 41511870
Pubmed 41511870

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