Gut. 2026 Oct 1:gutjnl-2026-339167. doi: 10.1136/gutjnl-2026-339167. Online ahead of print.
ABSTRACT
BACKGROUND: The impact of circulating tumour DNA (ctDNA) detection, which informs minimal residual disease (MRD) after curative treatment, remains debated especially for stage IV patients.
OBJECTIVE: The study objectives were to evaluate the prognostic role of MRD and to estimate lead time (LT) at different timepoints when adopting longitudinal MRD testing.
DESIGN: INTERCEPT, is a prospective, observational cohort study of stage II-IV patients with colorectal cancer receiving curative-intent treatment who are longitudinally monitored using tissue-informed MRD assays as part of routine clinical care.
RESULTS: Study results confirm the prognostic value of MRD, also beyond 12 months from surgery, with higher recurrence incidence in MRD-positive stage II-III patients than in MRD-negative stage IV patients (p<0.0001). Adjuvant therapy in stage IV disease showed limited durable benefit in both MRD-positive and negative patients. Clinical management was associated with increased use of more intensive second-line imaging (MRI, positron emission tomography; p<0.0001) when ctDNA was detected. Concurrent macroscopic disease detection was observed in 26% of cases and when excluded, LT from MRD detection to radiographic recurrence varies during surveillance (p=0.007). Multitimepoint testing improves sensitivity for recurrence (79.9% vs 48.5%) and may enable earlier, potentially curative interventions.
CONCLUSION: ctDNA testing provides a framework for risk stratification and defines temporal windows that may inform future interventional strategies. Prospective interventional studies are required to define clinical utility and optimal implementation.
PMID:42823331 | DOI:10.1136/gutjnl-2026-339167