Cancer Genetics and Epigenetics, 2025, Vol.13, No.6, 287-299 http://medscipublisher.com/index.php/cge 287 Feature Review Open Access Postoperative Recurrence Monitoring and ctDNA-Guided Intervention in Colorectal Cancer Patients Liqin Guo, Jiayi Wu Biotechnology Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China Corresponding author: jiayi.wu@cuixi.org Cancer Genetics and Epigenetics, 2025, Vol.13, No.6 doi: 10.5376/cge.2025.13.0029 Received: 25 Sep., 2025 Accepted: 30 Oct., 2025 Published: 11 Dec., 2025 Copyright © 2025 Guo and Wu, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Guo L.Q., and Wu J.Y., 2025, Postoperative recurrence monitoring and ctDNA-guided intervention in colorectal cancer patients, Cancer Genetics and Epigenetics, 13(6): 287-299 (doi: 10.5376/cge.2025.13.0029) Abstract This study mainly discusses the causes and related risk factors of tumor recurrence after colorectal cancer surgery, and points out the deficiencies of the commonly used follow-up methods at present. Circulating tumor DNA (ctDNA) plays a significant role in detecting a small amount of residual cancer cells (MRD) after tumor resection and predicting whether recurrence will occur. Positive ctDNA after surgery is the most crucial recurrence signal, which is less disturbed by other factors and can often detect recurrence tendencies at the molecular level several months earlier than imaging examinations. By constantly monitoring ctDNA changes, it is possible to more accurately and sensitively assess the risk of recurrence, promptly understand the treatment effect, and also identify genetic alterations that lead to drug resistance (such as RAS gene mutations), thereby assisting doctors in formulating more appropriate and individualized treatment plans for patients. This study also arranged postoperative treatment steps based on the ctDNA test results, and there were multiple important clinical trial results as evidence. Although there are still some practical problems in the routine clinical application, ctDNA has great application prospects in improving postoperative monitoring methods and assisting treatment decisions. In the future, more related products with better performance are also expected to emerge. Keywords Circulating tumor DNA (ctDNA); Minimal residual disease (MRD); Postoperative recurrence in colorectal cancer; Dynamic molecular monitoring; ctDNA-Guided personalized therapy 1 Introduction Colorectal cancer is one of the common malignant tumors worldwide, and the number of related deaths is also relatively large. It has become an important public health problem (Abidoye et al., 2025). Although surgery and comprehensive treatment have been constantly advancing, many patients still experience relapses after radical surgery. For patients with severe local conditions or existing metastases (such as liver metastases), the risk of recurrence is particularly obvious, and the recurrence rate within two years can approach 70% (Kalil et al., 2024). Even for patients in stage II or III, approximately 20% to 40% will relapse after surgery, with the majority occurring within three years after the operation. Therefore, more effective monitoring methods are needed to detect problems as early as possible when the condition just changes, so as to adjust the treatment plan in time and improve the long-term survival chance (Abidoye et al., 2025). The commonly used methods for monitoring colorectal cancer recurrence in the past, such as imaging examinations and serum carcinoembryonic antigen detection, have always been the main means of postoperative follow-up. However, these methods have many shortcomings, which affect their effectiveness in the early detection of lesions and risk assessment. Although imaging examinations such as computed tomography can detect obvious lesions, they are not sensitive enough for mild and newly emerged recurrence cases, often delaying diagnosis and missing the best treatment opportunity (Kalil et al., 2024). In addition, sometimes the imaging results are unclear and difficult to judge, and may even require patients to undergo some unnecessary further examinations. Carcinoembryonic antigen (CEA) is widely used as a tumor marker, but its accuracy and reliability are not good enough: many patients with normal CEA indicators will still relapse, and false positive results will cause patients to worry in vain and require additional tests. At present, the optimal examination frequency and duration of imaging and CEA monitoring have not been determined, and the actual help of enhanced monitoring for patient survival is also unclear. Therefore, the recurrence of many patients is discovered only when the disease
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