Risk stratification by minimal residual disease detection and ctDNA dynamics from personalised assays in stage II-III colorectal cancer in a UK multi-centre prospective study (TRACC Part B)

Risk stratification by minimal residual disease detection and ctDNA dynamics from personalised assays in stage II-III colorectal cancer in a UK multi-centre prospective study (TRACC Part B) | Research Square Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Risk stratification by minimal residual disease detection and ctDNA dynamics from personalised assays in stage II-III colorectal cancer in a UK multi-centre prospective study (TRACC Part B) Susanna Slater, Christopher CT Sng, Gayathri Anandappa, Hsiang-Chi Chen, and 23 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8574150/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Circulating tumour DNA (ctDNA) detects minimal residual disease (MRD) and predicts recurrence in resected colorectal cancer (CRC), with implications for adjuvant chemotherapy (ACT) decision-making. Longitudinal ctDNA quantification and dynamics are less well studied. We present results from the ongoing prospective multi-centre TRACC study using a tumour-informed ctDNA assay. Methods TRACC Part B recruited stage I-III CRC patients undergoing curative surgery +/- neo-adjuvant (chemo)radiotherapy and ACT. Blood samples were collected pre-treatment, post-operatively, 3-monthly for year 1 and 6 monthly for years 2–3, with annual imaging. We report a cohort with stage II-III CRC ( n = 122), including a subset with locally advanced rectal cancers ( n = 23). Plasma samples were analysed using a personalisedmultiplex polymerase chain reaction next-generation sequencing (mPCR-NGS) ctDNA assay (Signatera™) targeting mutated loci identified in tumour tissue. The primary endpoint was recurrence-free survival (RFS) by ctDNA status. Exploratory objectives included ctDNA quantification and dynamics. Median follow-up was 35 months (range: 2–64). (NCT04050345) Results Of 122 patients, library preparation for whole exome sequencing of primary tumour tissue was possible in 116. Pre-treatment ctDNA detection rate was 94.0% (109/116). ctDNA detection rate 2–8 weeks post-operatively (MRDpos) was 12.1% (14/116); 10.9% in stage III (23.8% high-risk, 4.7% low-risk) and 13.5% in stage II (23.5% high-risk, 8.6% low-risk). Of MRDpos patients, 78.6% (11/14) recurred. Overall, 18.6% (19/102) MRD negative (MRDneg) patients recurred. Twenty-four-month RFS was 30.8% in MRDpos versus 88.1% in MRDneg patients (HR 8.4, 95% CI 4–18; p < 0.001). In a multivariate analysis, ctDNA detection remained the most significant prognostic factor (HR 7.2, 95% CI 2.94–17.6; p < 0.001)followed by nodal stage (HR 2.58, 95% CI 1.01–6.6; p = 0.047). Among high-risk CRC, ACT conferred survival benefit only in MRDpos patients. Longitudinal ctDNA sampling identified relapse with 80% sensitivity. ctDNA concentration increased exponentially prior to recurrence ( n = 11). ctDNA growth rate was prognostic of RFS (p = 0.021). ctDNA detection was lower in patients with lung-only metastases. Conclusions Post-operative and longitudinal tumour-informed ctDNA testing identifies patients at high CRC recurrence risk and may guide ACT decisions. Further studies are needed to establish the interpretation and utility of longitudinal ctDNA quantification and dynamics to personalise patient management. Colorectal cancer (CRC) circulating tumour DNA (ctDNA) liquid biopsy minimal residual disease (MRD) ctDNA dynamics recurrence Full Text Additional Declarations No competing interests reported. Supplementary Files TRACCNateraSuppMaterialFinaldraft110126CL.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information

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