A 14-Gene Panel for Predicting Colorectal Cancer Recurrence Using Circulating Tumor DNA in Different Testing Conditions.

Detecting minimal residual disease after surgery is critical for assessing colorectal cancer recurrence risk. Traditional methods, including histology and carcinoembryonic antigen testing, have limited sensitivity. As circulating tumor DNA has emerged as a promising minimal residual disease biomarker, we evaluated circulating tumor DNA detection using a sensitive, targeted 14-gene panel, the Sysmex Plasma-Safe-SeqS colorectal cancer assay, in resectable colorectal cancer cases. We enrolled 46 Japanese patients with preoperatively diagnosed stage II colorectal cancer who underwent surgery at three institutions. Plasma samples were collected pre- and postoperatively. Tumor-informed, plasma-informed, and tumor-naive Plasma-Safe-SeqS colorectal cancer assays were performed. Patients were followed for a median of 1169 (range 148-1476) days using clinical assessments and computed tomography scans. Variants in tumor tissue were detected in 45 of 46 cases (98%). Preoperative circulating tumor DNA was detected in 32 (70%) and postoperative circulating tumor DNA in 16 (35%) patients. Postoperative circulating tumor DNA predicted recurrence with 33%, 38%, and 25% of positive percent agreement for tumor-informed, plasma-informed, and tumor-naive assays, respectively. The tumor-naive assay detected more postoperative circulating tumor DNA-positive cases than the others. As the tumor-naive approach does not require preoperative genetic profiling, it offers significant advantages in cost and ease of implementation in routine clinical practice. Further large-scale studies are warranted to optimize detection strategies.