Validation of a methylation-based, tissue-free MRD assay in colorectal cancer patients from the GALAXY study

assay) for detecting molecular residual disease (MRD) in colorectal cancer (CRC), analyzing data from 195 patients (1230 timepoints) from the observational GALAXY study. The assay demonstrated that ctDNA-positivity correlated with significantly worse disease-free survival (DFS) in both the MRD (HR = 10.0, P < 0.001) and post-definitive treatment surveillance windows (HR = 31.9, P < 0.001). In the MRD window, the assay demonstrated a sensitivity of 58.5% (38/65), while the specificity in patients who did not receive adjuvant chemotherapy (ACT) was 100% (63/63). Longitudinally, relapse was detected with a sensitivity of 84.4% (54/64), with high specificity at the patient (92.1%; 116/126) and sample (97.2%; 619/637) levels. Median lead time from first circulating tumor DNA (ctDNA)-positive result to relapse was 4.6 months. For high-risk stage II and III CRC, ctDNA-positive patients benefited from ACT (adj.HR = 0.014, P < 0.0001), unlike ctDNA-negative patients. These findings highlight the robust prognostic and predictive capabilities of this tissue-free MRD assay in CRC patients.