Evolution of non-invasive colorectal neoplasm detection

Abstract

Colorectal cancer (CRC) is one of the leading cancers worldwide in terms of both incidence and mortality. Colonoscopy remains the most accurate and effective method for early detection and screening of CRC, and it also enables CRC prevention by removing adenomas. However, because it is an invasive procedure that requires bowel preparation and carries risks of discomfort and complications, various non-invasive diagnostic tools have been developed as alternatives. These tools use stool, blood, urine, and breath samples, with a particular focus on biomarkers targeting DNA methylation. Currently, strategies that combine multiple biomarkers are under development. Biomarker selection is increasingly guided by machine learning based on next-generation sequencing data. In particular, the concept of multi-omics has played a pivotal role in this development, and many novel diagnostic tools are expected to be validated in large-scale clinical trials. This review aims to enhance our understanding of the principles behind diagnostic tools for early CRC detection by outlining colorectal carcinogenesis and providing an overview of the evolution of CRC screening strategies.

Keywords: Blood; Colorectal neoplasms; DNA methylation; Feces; Screening

Core Tip: Non-invasive colorectal cancer (CRC) screening modalities have been developed as alternatives to colonoscopy to improve patient compliance and reduce procedural risks. DNA methylation biomarkers are the key high-performing component of non-invasive CRC screening tests based on stool and blood. Recent advances in next-generation sequencing and machine learning have enabled the integration of multi-omics data into non-invasive CRC screening, facilitating the development of diverse biomarker-based tests across multiple sample types.