Cancer Genetics and Epigenetics, 2025, Vol.13, No.6, 287-299 http://medscipublisher.com/index.php/cge 292 warning can buy critical time for treatment and may even control the condition through radical salvage therapy before the metastatic lesions are detected by imaging and before the patient shows symptoms (Xu et al., 2025;). The accuracy of dynamic ctDNA monitoring is very high. In many studies, its sensitivity and specificity have exceeded 80%~90% (Mo et al., 2023; Slater et al., 2024; Hashimoto et al., 2025). Continuous monitoring of changes in ctDNA can help determine the condition of the tumor and whether the treatment is effective. Whether ctDNA can turn negative or remain positive during or after adjuvant therapy has a strong relationship with the recurrence risk and survival status of patients (Abidoye et al., 2025; Hashimoto et al., 2025). Patients whose ctDNA turns negative during the treatment process will recover better. If the ctDNA level is persistently high or continuously rising, it indicates a relatively high risk of recurrence, and enhanced treatment or adjustment of treatment methods may be required (Mo et al., 2023). In addition, the rate at which ctDNA rises can also reflect the urgency of the disease change - the faster it rises, the faster the disease may deteriorate. Therefore, incorporating dynamic ctDNA monitoring in postoperative follow-up can detect signs of recurrence earlier and more accurately, and arrange more effective and personalized treatment plans for colorectal cancer patients. 5 Postoperative Treatment Strategies Guided by ctDNA 5.1 Adjust the intensity of adjuvant therapy based on the ctDNA results In the postoperative follow-up of colorectal cancer, circulating tumor DNA (ctDNA) testing can help doctors formulate more targeted adjuvant treatment plans. Doctors can determine whether there is a minimal residual tumor based on the ctDNA result. A positive ctDNA indicates a higher risk of recurrence, and most patients need to enhance or extend treatment. A negative ctDNA indicates a lower risk. Adjuvant chemotherapy can be considered to be reduced or even omitted, and the treatment intensity can be controlled more flexibly, thereby reducing toxic and side effects and avoiding overtreatment (Kotani et al., 2023; Negro et al., 2025). In the DYNAMIC trial of stage II colon cancer, after treatment guided by ctDNA results, the proportion of patients receiving adjuvant chemotherapy decreased from 28% of the standard regimen to 15%, but the recurrence-free survival period was not shortened, indicating that reducing the treatment for ctDNA-negative patients is relatively safe. In some dynamic rectal studies of advanced rectal cancer, ctDNA result adjustment regimens also significantly reduced the use of chemotherapy, and the recurrence-free survival rate of patients was similar to that of conventional treatment (Tie et al., 2024). Conversely, for patients with positive ctDNA and a high risk of recurrence, more intensive adjuvant therapy may be required to improve prognosis. The Dynamical-III trial for stage III colon cancer attempts to provide ctDNA-positive patients with stronger treatment regimens, such as switching from a single fluoropyrimidine drug to dual-drug or triple-drug chemotherapy containing oxaliplatin. Although the intensification regimen did not significantly improve the recurrence-free survival rate compared with the standard treatment, this study once again demonstrated the predictive value of ctDNA and also suggested that we still need to find more effective intensification treatment methods. Overall, adjusting the treatment intensity based on ctDNA has great potential in optimizing adjuvant therapy, reducing toxic and side effects, and improving the prognosis of patients with colorectal cancer (Kotani et al., 2023; Tie et al., 2024; Negro et al., 2025). 5.2 Intervention measures for ctdna positive patients After the patient has completed surgery or adjuvant therapy, if ctDNA remains positive continuously, it is generally considered that the risk of recurrence is relatively high, and there may still be small metastases in the body that are difficult to detect by imaging and not easy to clear by conventional chemotherapy (Figure 2) (Kotani et al., 2023; Burley et al., 2024). At this point, chemotherapy can be moderately strengthened on the existing basis, or new drugs can be tried to increase the chance of eliminating residual lesions. The DYNAMIC-III trial evaluated the efficacy of the intensive regimen in patients with ctDNA-positive stage III colon cancer, but it did not significantly improve the recurrence-free survival rate compared with the standard treatment. Therefore, further exploration of more appropriate intensive strategies is still needed (Tie et al., 2025; Zhou et al., 2025). At present, interventions based on ctDNA results have gradually expanded to targeted therapy and immunotherapy, especially for patients with specific genetic alterations.
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