Cancer Genetics and Epigenetics, 2025, Vol.13, No.6, 287-299 http://medscipublisher.com/index.php/cge 291 imaging examinations or blood marker tests (Mo et al., 2023). It is worth mentioning that through ctDNA detection of MRD, the recurrence risk of patients can be determined 3 to 7 days after surgery. Thus, doctors can promptly formulate personalized adjuvant chemotherapy plans and monitoring plans for patients (Chidharla et al., 2023; Mo et al., 2023; Hashimoto et al., 2025). Early detection of a small amount of residual lesions in the body after surgery helps doctors assess the condition and arrange subsequent treatment. If the ctDNA test is positive, it indicates a relatively high risk of recurrence, and usually requires enhanced treatment or a shortened follow-up interval. A negative ctDNA indicates a lower risk of recurrence. Chemotherapy intensity or course can be appropriately reduced to minimize unnecessary toxic and side effects (Negro et al., 2025). This approach makes the treatment more targeted and reduces obvious overtreatment. Further combining the ctDNA test results with clinicopathological indicators to establish a recurrence prediction model can more accurately assess the recurrence risk and provide a reference for formulating an appropriate postoperative management plan (Gao et al., 2023). 4.2 Positive ctDNA indicates a significantly increased risk of recurrence If the ctDNA test result is positive after surgery or adjuvant therapy, it means that the patient's risk of recurrence will increase significantly. Comprehensive analysis and large-scale cohort studies have shown that the recurrence risk of ctDNA positive patients is 7 to 17 times higher than that of CTDNA negative patients. In some studies, the recurrence rate of such patients even exceeds 70% - 80%. Even after excluding known clinicopathological risk factors, this high risk still exists, which indicates that ctDNA is the most crucial and independent indicator for judging recurrence-free survival (Chidharla et al., 2023; Mo et al., 2023). It is particularly important to note that for patients whose ctDNA remains positive after adjuvant therapy, the prognosis is especially poor, with a recurrence risk ratio exceeding 10 times. Such patients need to change or enhance their treatment plans. ctDNA testing has a high degree of accuracy, especially when the result is positive, it can better indicate the risk of disease progression and recurrence. Studies have shown that the recurrence rate of ctDNA-positive patients significantly increases at key postoperative time points, while most ctDNA-negative patients have relatively stable conditions over a long period of time. This helps doctors identify high-risk populations as early as possible and adjust treatment and follow-up arrangements (Mo et al., 2023; Abidoye et al., 2025). Therefore, the inclusion of ctDNA testing in postoperative follow-up is regarded as an important advancement in the diagnosis and treatment of colorectal cancer and can be used as a non-invasive, repeatable and relatively comprehensive recurrence risk assessment marker (Figure 1) (Chidharla et al., 2023; Hashimoto et al., 2025; Negro et al., 2025). Figure 1 Forest plot showing the pooled hazard ratio based on the ctDNA method based on post-adjuvant ctDNA positive versus ctDNA-negative status (Adopted from Chidharla et al., 2023) Image caption: The hazard ratio for each adverse event is represented by a square, and the horizontal lines crossing the squares represent the 95% confidence interval (CI) (Adopted from Chidharla et al., 2023) 4.3 Dynamic ctDNA monitoring can detect recurrence several months earlier than imaging Continuous and dynamic monitoring of ctDNA after surgery or adjuvant therapy can detect molecular-level recurrence several months earlier than the appearance of clinical symptoms or imaging abnormalities. Multiple prospective studies have shown that ctDNA testing can detect signs of recurrence 3 to 10 months earlier than conventional tests such as CT and carcinoembryonic antigen (CEA) testing (Negro et al., 2025). This early
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