Clinical impact of prospective circulating tumour DNA testing for minimal residual disease in colorectal cancer: the INTERCEPT programme experience

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.