Circulating tumor DNA as a predictor of response and prognosis in rectal cancer treated with total neoadjuvant therapy (JCOG2010A1-ctTNT study)

JCOG2010A1 is a multi-institutional prospective observational study evaluating circulating tumor DNA (ctDNA) as a biomarker for minimal residual disease (MRD) detection in rectal cancer patients undergoing total neoadjuvant therapy (TNT) with active surveillance. This companion study to the JCOG2010 phase II/III trial addresses a critical clinical challenge: determining optimal treatment pathways between surgery and non-operative management following TNT. While TNT with active surveillance represents a promising organ-preserving strategy for patients achieving clinical complete response, reliable biomarkers for residual disease assessment remain lacking. ctDNA has emerged as a highly sensitive biomarker for MRD detection across multiple cancer types. The Signatera™ personalized tumor-informed assay will be utilized for ctDNA analysis throughout the treatment journey, potentially enabling more precise, individualized decision making.<ul><li>•Collect baseline tumor tissue and blood samples, followed by serial plasma collection at predetermined timepoints throughout the protocol treatment period, including post-TNT assessment and during active surveillance.</li><li>•Analyze ctDNA using the Signatera™ personalized tumor-informed assay to detect minimal residual disease after TNT, with results correlated to clinical and radiological findings.</li><li>•Compare recurrence-free survival, organ preservation rates, and overall survival based on ctDNA status at multiple timepoints to assess its utility as a prognostic and predictive biomarker for treatment decision making.</li></ul>