Evaluation of Molecular Residual Disease by a Fixed Panel in Resectable Colorectal Cancer

Area of Science:

• Oncology
• Molecular Biology
• Cancer Biomarkers

Background:

• Molecular residual disease (MRD) is a key prognostic biomarker in colorectal cancer (CRC).
• Whole-exome sequencing (WES)-based tumor-informed assays are standard for MRD detection using circulating tumor DNA (ctDNA).
• Assessing the feasibility of fixed-panel assays for MRD evaluation in CRC is crucial for clinical application.

Purpose of the Study:

• To evaluate the feasibility of a fixed-panel assay for MRD detection in colorectal cancer (CRC).
• To compare the performance of fixed-panel assays against personalized assays for ctDNA evaluation.
• To determine the prognostic value of ctDNA positivity for disease-free survival (DFS) in CRC patients.

Main Methods:

• Seventy-five patients with resectable stage I-III CRC were enrolled.
• Tumor tissues and serial blood samples (preoperative and postoperative day 7) were collected.
• ctDNA was analyzed using tumor-agnostic/informed fixed assays and WES-based/panel-based personalized assays.

Main Results:

• The tumor-informed fixed assay demonstrated a higher preoperative positive rate (73.3%) than the tumor-agnostic assay (57.3%).
• Postoperative day 7 ctDNA positivity by the tumor-informed fixed assay significantly predicted worse DFS (HR, 20.74; p < 0.001) and was an independent predictor.
• Personalized assays and the tumor-informed fixed assay showed similar prognostic performance for DFS, outperforming the tumor-agnostic fixed panel.

Conclusions:

• The study confirms the prognostic significance of ctDNA positivity on postoperative day 7 using a tumor-informed fixed panel in CRC.
• The tumor-informed fixed panel emerges as a potentially cost-effective method for MRD evaluation in CRC.
• Further research is warranted to validate the clinical utility of the tumor-informed fixed panel for MRD monitoring.