Updates on the use of ctDNA in the management of colorectal cancer

Colorectal cancer (CRC) remains a major global health concern as the third most diagnosed cancer and the second leading cause of cancer-related deaths. While early detection through colonoscopy and stool-based screening significantly improves survival, limited adherence and diagnostic sensitivity highlight the need for better non-invasive tools. Circulating tumor DNA (ctDNA), a tumor-specific component of cell-free DNA, has emerged as a promising biomarker that may transform the detection, monitoring, and treatment of CRC. This review compiles and summarizes recent advancements and updates in ctDNA research and evaluates its clinical utility across CRC management. Recent clinical trials, biomarker studies, and comprehensive reviews were examined to evaluate recent advancements in the use of ctDNA in CRC detection and management. ctDNA methylation-based assays have shown high diagnostic accuracy, especially in late-stage CRC, with several multi-gene panels achieving sensitivities and specificities above 90%. Large-scale studies such as DYNAMIC II, GALAXY, and BESPOKE CRC support ctDNA’s role in identifying minimal residual disease (MRD), predicting recurrence, and informing adjuvant treatment decisions. Multiple studies have shown that ctDNA has outperformed carcinoembryonic antigen (CEA) and imaging in CRC surveillance, detecting relapse months in advance. Economic analyses suggest that integrating ctDNA testing into clinical workflows may reduce overall treatment costs by minimizing overtreatment. The results of several major ongoing trials are awaited and are expected to further inform the role of ctDNA in routine CRC care. ctDNA offers a minimally invasive, real-time approach to personalize CRC management across all disease stages. Although challenges remain, particularly in standardization, early-stage detection, and optimal timing of testing, ongoing research continues to support its expanding role in precision oncology.