Molecular residual disease (MRD) detection using an ultra-sensitive assay in a prospective colorectal cancer cohort: The VICTORI study.

3629 Background: Circulating tumor DNA (ctDNA) detection of molecular residual disease (MRD) is prognostic in colorectal cancer (CRC) but missed recurrences highlight constraints in assay performance. VICTORI is a prospective observational study investigating an ultrasensitive MRD assay (NeXT Personal) in CRC patients undergoing curative treatment. Methods: Whole-genome informed panels of ~1,800 variants interrogated plasma collected pre-curative loco-regional treatment, q2 weeks post-surgery (weeks 2–8, landmark window), and subsequently every 3 months (3-36 months, surveillance window). Results: 795 plasma samples from 109 patients were analyzed, with median follow-up of 21.1 months and 31 recurrences observed. Cohort characteristics: 61 (56.0%) rectal cancer, 48 (44.0%) colon cancer; 81 (74.3%) stage I-III; 56 (50.5%) had neoadjuvant treatment; 106 (97.2%) had surgery as curative procedure. Pre-surgical sensitivity (treatment-naïve) was 96.0% (n=48/50) and specificity was 100% (no detection in pathologic complete responders; 0/10). Landmark window overall sensitivity for recurrence was 83.9% (n=26/31) with 69.2% (18/26) of detections being