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

doi:10.1093/bjs/znaf281

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^*,

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	znaf281
Number of pages	10
Journal	The British journal of surgery
Volume	113
Issue number	1
DOIs	https://doi.org/10.1093/bjs/znaf281
Publication status	Published - Jan 2026

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

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Circulating tumour DNA in patients with stage III colon cancer: multicentre prospective PROVENC3 study Final published version, 356 KBLicence: CC BY

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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. (2026). Circulating tumour DNA in patients with stage III colon cancer: multicentre prospective PROVENC3 study. The British journal of surgery, 113(1), Article znaf281. https://doi.org/10.1093/bjs/znaf281

@article{11509fe178bc4d4da6f6c1c859f5de55,

title = "Circulating tumour DNA in patients with stage III colon cancer: multicentre prospective PROVENC3 study",

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{\textregistered} Plasma Detect{\texttrademark}, 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",

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

note = "Publisher Copyright: {\textcopyright} 2026 The Author(s). ",

year = "2026",

month = jan,

doi = "10.1093/bjs/znaf281",

language = "English",

volume = "113",

journal = "The British journal of surgery",

issn = "0007-1323",

publisher = "24150509",

number = "1",

}

Rubio-Alarcón, C, Georgiadis, A, Franken, IA, Wang, H, van Nassau, SCMW, Schraa, SJ, van der Kruijssen, DEW, van Rooijen, K, Linders, TC, Delis-van Diemen, P, Alkemade, M, Bolijn, A, Tijssen, M, Lemmens, M, Meiqari, L, Ketelaars, SLC, Closa-Mosquera, A, van Dongen, MMW, Lanfermeijer, M, Lissenberg-Witte, BI, Bosch, LJW, Bisschop-Snetselaar, T, Adriaans, BC, Greer, A, Riley, D, White, JR, Greco, C, Cox, L, Fox, J, Victor, K, Leech, C, Angiuoli, SV, Kok, NFM, Punt, CJA, van den Broek, D, Koopman, M , Meijer, GA, Velculescu, VE, Roodhart, JML, Coupé, VMH, Sausen, M, Vink, GR, Fijneman, RJA 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

TY - JOUR

T1 - Circulating tumour DNA in patients with stage III colon cancer

T2 - multicentre prospective PROVENC3 study

AU - Rubio-Alarcón, Carmen

AU - Georgiadis, Andrew

AU - Franken, Ingrid A

AU - Wang, Haoyue

AU - van Nassau, Sietske C M W

AU - Schraa, Suzanna J

AU - van der Kruijssen, Dave E W

AU - van Rooijen, Karlijn

AU - Linders, Theodora C

AU - Delis-van Diemen, Pien

AU - Alkemade, Maartje

AU - Bolijn, Anne

AU - Tijssen, Marianne

AU - Lemmens, Margriet

AU - Meiqari, Lana

AU - Ketelaars, Steven L C

AU - Closa-Mosquera, Adria

AU - van Dongen, Miranda M W

AU - Lanfermeijer, Mirthe

AU - Lissenberg-Witte, Birgit I

AU - Bosch, Linda J W

AU - Bisschop-Snetselaar, Teunise

AU - Adriaans, Bregje C

AU - Greer, Amy

AU - Riley, David

AU - White, James R

AU - Greco, Christopher

AU - Cox, Liam

AU - Fox, Jesse

AU - Victor, Kaitlin

AU - Leech, Catherine

AU - Angiuoli, Samuel V

AU - Kok, Niels F M

AU - Punt, Cornelis J A

AU - van den Broek, Daan

AU - Koopman, Miriam

AU - Meijer, Gerrit A

AU - Velculescu, Victor E

AU - Roodhart, Jeanine M L

AU - Coupé, Veerle M H

AU - Sausen, Mark

AU - Vink, Geraldine R

AU - Fijneman, Remond J A

PY - 2026/1

Y1 - 2026/1

N2 - 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.

AB - 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.

KW - Aged

KW - Aged, 80 and over

KW - Biomarkers, Tumor/blood

KW - Chemotherapy, Adjuvant

KW - Circulating Tumor DNA/blood

KW - Colonic Neoplasms/pathology

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Neoplasm Recurrence, Local

KW - Neoplasm Staging

KW - Neoplasm, Residual

KW - Prognosis

KW - Prospective Studies

U2 - 10.1093/bjs/znaf281

DO - 10.1093/bjs/znaf281

M3 - Article

C2 - 41511870

SN - 0007-1323

VL - 113

JO - The British journal of surgery

JF - The British journal of surgery

IS - 1

M1 - znaf281

ER -

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

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