Using Circulating Tumor DNA to Guide Neoadjuvant Treatment for Locally Advanced Rectal Cancer A Phase 2 Multicenter Randomized Controlled Trial

What this Trial Is About

Locally advanced rectal cancer remains a common tumor with a high rate of distant metastasis and unsatisfactory long-term survival. Researchers are evaluating a new treatment approach using circulating tumor DNA ctDNA to guide neoadjuvant therapy intensity and immunotherapy use. This phase 2 multicenter randomized trial aims to improve treatment precision and outcomes by tailoring therapy based on ctDNA tumor burden and genetic markers. Participants with rectal adenocarcinoma staged as cT3-4N0 or cTanyN are randomized into two groups. The control group receives traditional neoadjuvant chemoradiotherapy with oral capecitabine and radiotherapy. The experimental group receives treatment guided by ctDNA variant allele frequency VAF and genetic sequencing, including immunotherapy with Terelizumab for patients with MSI-H or TMB-H mutations, or neoadjuvant chemoradiotherapy or total neoadjuvant therapy based on ctDNA levels. Throughout the study, participants will undergo tumor tissue sequencing, immune marker analysis, and regular assessments including clinical complete response, pathological response, survival, and quality of life over up to 5 years. The primary outcome is two-year disease-related treatment failure. Safety, recurrence, and other outcome measures will also be monitored. The study seeks to optimize treatment plans and reduce adverse effects by using precision medicine guided by ctDNA.

Circulating Tumor DNA-guided Neoadjuvant Treatment Strategy for Locally Advanced Rectal Cancer