Association of Recurrence with a Tumor-informed Personalized ctDNA Detection Approach in Resectable Colorectal Cancer

Objective: Primary objective was to evaluate the association between post-surgical MRD detected by a tumor-informed personalized panel (brPROPHET) and CRC recurrence, Secondary objectives were to determine the optimal timepoint for MRD assessment, and compare the performance of different MRD detection methods, including brPROPHET, a tumor-informed fixed panel (TIFP) and a tumor-naïve fixed panel (TNFP). Summary of Background Data: Circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) has emerged as a pivotal marker in colorectal cancer (CRC), but optimal detection timing and methods remain unclear. Methods: This study included patients with resectable stage I-IV CRC. Tumor tissues were obtained at surgery, and blood samples were collected preoperatively, on post-surgical days 7 and 30 (D7/D30), and every 3–6 months. MRD was assessed using the above three methods. Results: A total of 214 patients were included in the analysis, with imaging follow-up available for 196 patients (median follow-up: 18.2 months), among whom 24 (12.2%) experienced recurrence. MRD positivity at D7/D30 associated with significantly reduced disease-free survival (DFS). Longitudinal ctDNA-MRD positivity and MTM levels >0.01/mL were also associated with recurrence. Adjuvant chemotherapy was associated with better DFS in patients with positive MRD at D7 (HR=0.26, 95% CI 0.07–0.98, P =0.03) instead of those with negative MRD at D7. Among the 168 patients assessed with all three methods, the brPROPHET assay demonstrated better association of DFS at D7. Conclusions: ctDNA-based MRD detected by brPROPHET associates with recurrence in CRC. Day 7 is an effective alternative landmark to Day 30 for MRD assessment and brPROPHET outperforms TIFP and TNFP in the association of DFS. ClinicalTrials.gov number: NCT06143644.