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Recent findings highlight rapidly accumulating prospective trial data, with positive ctDNA status predicting recurrence and aligning with treatment guidelines. Evidence also supports roles in screening, multi-cancer early detection, and longitudinal surveillance, while randomized trial data remain 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\nREVIEW  \nFrom Early Detection To Advanced Therapies: How Circulating Tumor DNA Is Transforming the Care of Colorectal Cancer  \nElliott J. Yee1 · Martin D. McCarter1 · Jon D. Vogel1 · Richard D. Schulick1 · Christopher Lieu2 · Robert W. Lentz2  \nReceived: 22 August 2025 / Accepted: 29 September 2025 / Published online: 3 November 2025 © The Author(s) 2025  \nAbstract  \nPurpose of Review Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Liquid biopsy by peripheral blood circulating tumor DNA (ctDNA) measurement has emerged as a promising biomarker in the management ofCRC. We aimed to summarize the current landscape of ctDNA assessment in CRC by briefly addressing relevant technicalities ofctDNA assays, reviewing the current body of evidence regarding the utility of ctDNA across the clinical spectrum, and providing considerations and prospectus for the future ofctDNA in CRC.  \nRecent Findings Data from prospective trials investigating the use of ctDNA in CRC is rapidly accumulating. Positive ctDNA status is a strong prognostic factor for recurrence, now recognized in cancer treatment guidelines, and is emerging as a potential guide for adjuvant therapies in the setting of resected localized and metastatic disease. Mounting evidence also suggests that ctDNA measurement can potentially have a meaningful impact for CRC screening, multi-cancer early detection, and longitudinal surveillance of tumor biology in the setting of systemic therapies such as anti-EGFR rechallenge. There is a paucity of randomized controlled trial data supporting ctDNA use.  \nSummary ctDNA assessment may improve the clinician’s ability to gain granular information about tumor biology and activity across the spectrum ofCRC. The results of ongoing randomized trials will further inform the value of routine ctDNA testing while helping steer future investigation  \nKeywords Colorectal cancer · CtDNA · Liquid biopsy · Tumor marker  \nIntroduction  \nBiomarker-based assessment of malignant disease activity is fundamental to managing solid organ tumors [1] . For colorectal cancer (CRC), third-most common cancer globally by incidence and second most common cause of cancer death globally, non-invasive methods to monitor tumor biology and predict outcomes are crucial [2] . The ability to characterize genetic and molecular profiles of individual  \n􀀍 Elliott J. Yee [elliott.yee@cuanschutz.edu](elliott.yee@cuanschutz.edu)  \n1 Division of Surgical Oncology, Department of Surgery, Anschutz Medical Campus, University of Colorado, 12801  \nE. 17Th Avenue, Aurora, CO 80045, USA  \n2 Division of Medical Oncology, Department of Medicine, Anschutz Medical Campus, University of Colorado, 12801  \nE. 17Th Avenue, Aurora, CO 80045, USA  \ntumors and personalize treatment defines the march toward precision oncology.  \nIn the past five years, circulating tumor DNA (ctDNA), a liquid biopsy of the peripheral blood, has emerged as a powerful bio-informant for CRC [3] . Due to the clinical and biological diversity of CRC, which warrant a combination of treatment modalities, dynamic biomarker assessment through ctDNA has proven particularly valuable. Studies suggest that contemporary ctDNA assays, primarily powered by next-generation genomic sequencing, may outperform traditional biochemical markers like carcinoembryonic antigen (CEA) and conventional imaging in detecting residual and recurrent disease [4] . ctDNA may also be useful in screening for early detection, guiding adjuvant therapy decisions, and identifying optimal candidates for targeted treatments for advanced CRC. For rectal cancer, the advent of total neoadjuvant therapy (TNT), neoadjuvant immunotherapy for microsatellite instability-high (MSI-H) tumors, and non-operative management presents  \nan additional opportunity for ctDNA assessment of tumor activity, potentially impacting clin","cbCaigo1FGKHhF1c","https://ap.wps.com/l/cbCaigo1FGKHhF1c","pdf",1586605,11,"English","# Review Overview\n## Purpose of Review\n## Recent Findings\n## Summary\n# Introduction\n## Biomarker-based monitoring in CRC\n## Rise of ctDNA in the past five years\n# Technical Considerations: Liquid Biopsy, ctDNA, and cfDNA\n## Liquid biopsy principles\n## ctDNA assay basis and fragment characteristics","[{\"question\":\"What is the main goal of ctDNA assessment in colorectal cancer, according to the review?\",\"answer\":\"The review aims to summarize how ctDNA liquid biopsy supports management across the CRC spectrum by clarifying assay technicalities, evaluating clinical evidence, and outlining future prospects.\"},{\"question\":\"Why is positive ctDNA status important for colorectal cancer outcomes?\",\"answer\":\"Positive ctDNA status is described as a strong prognostic factor for recurrence and is recognized in cancer treatment guidelines.\"},{\"question\":\"What are the key limitations regarding the evidence for ctDNA use?\",\"answer\":\"The review notes a paucity of randomized controlled trial data supporting ctDNA use, even as prospective trial evidence continues to accumulate.\"}]","From Early Detection To Advanced Therapies: How Circulating Tumor DNA Is Transforming the Care of Colorectal Cancer - Review | PDF",1790193329,28]