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 S. Bolijn, Marianne Tijssen, Margriet Lemmens, Lana Meiqari, Steven L C Ketelaars, Adrià Closa, 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, V. Velculescu, Jeanine M.L. Roodhart, Veerle M.H. Coupé, Mark Sausen, Geraldine R Vink, Remond J A Fijneman, Other Members of the PLCRC-MEDOCC Group, M Los, J M van Dodewaard, M L R Tjin-A-Ton, A H W Schiphorst, M Koopman, P J Tanis, K Talsma, H B A C Stockmann, D D E Zimmerman, W J Vles, L B J Valkenburg, R C Rietbroek, E J Th Belt, J W T Dekker, I H J T de Hingh, R W M Schrauwen, F J F Jeurissen, R Hoekstra, M P Hendriks, J Jansen, J Konsten, P Nieboer, N A J B Peters, J F M Pruijt, L Simkens, A I de Vos, A Schouten van der Velden, A W Haringhuizen, M A Davidis, J Janssen
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.