INVESTIGATOR PERSPECTIVES Application of a Tissue-Free Epigenomic Assay to Improve MRD Detection in Previously Treated CRC

Yoshiaki Nakamura, MD, PhD, discusses how the use of tissue-free circulating tumor DNA (ctDNA) analysis for detecting minimal residual disease (MRD) can enhance the prediction of recurrence in stage II to III colorectal cancer (CRC), particularly when tumor specimens are limited.

Yoshiaki Nakamura, MD, PhD, discusses how the COSMOS-CRC-01 study was designed to evaluate the efficacy of ctDNA analysis for MRD detection, outlining the rationale for patient enrollment, the timing of plasma sample collection, and the implications for monitoring disease post surgery and during adjuvant chemotherapy.

Yoshiaki Nakamura, MD, PhD, discusses how the COSMOS-CRC-01 study demonstrated statistically significant recurrence-free intervals across various postoperative and adjuvant chemotherapy time points, highlighting the prognostic value of serial, tissue-free ctDNA assays for real-time detection of MRD vs single postchemotherapy assessments.

Yoshiaki Nakamura, MD, PhD, discusses how the COSMOS-CRC-01 study assessed the sensitivity and specificity of a cell-free DNA epigenomic assay in R0 stage II to III CRC, emphasizing the importance of monitoring minimal MRD to inform treatment decisions and the critical lead time between ctDNA positivity and radiographic disease recurrence.

Yoshiaki Nakamura, MD, PhD, discusses the quantification threshold for tissue-free ctDNA in detecting residual tumor fractions, highlights additional mutations and hypermethylated loci identified by epigenomic assays, and examines how these assays complement current radiographic monitoring in stage II to III CRC while also considering their evolving role in identifying MRD to enhance recurrence-free survival.