Cancer Genetics and Epigenetics, 2025, Vol.13, No.6, 287-299 http://medscipublisher.com/index.php/cge 288 has developed to a stage that is difficult to cure. This further indicates that we need more sensitive and accurate biomarkers to achieve early diagnosis and personalized postoperative management (Abidoye et al., 2025). This study will explore the role of circulating tumor DNA (ctDNA) in the monitoring of postoperative recurrence of rectal cancer and analyze its impact on postoperative management of patients. Multiple studies have shown that a positive ctDNA result after surgery significantly increases the risk of recurrence by approximately 7 to 10 times, and is less affected by other clinical factors. The predictive accuracy of ctDNA positivity for recurrence is also very high. By regularly monitoring changes in ctDNA, signs of recurrence can often be detected several months earlier than through imaging examinations or clinical symptoms, leaving doctors with earlier time for intervention. Although there are still deficiencies in terms of detection sensitivity, cost and integration with clinical data at present, the value of ctDNA in precise postoperative monitoring has been widely accepted. In the future, it is expected to become a commonly used method for monitoring postoperative recurrence of colorectal cancer, promoting more individualized treatment and follow-up strategies. 2 Mechanisms and Risk Factors of Postoperative Recurrence 2.1 Biological basis of tumor micrometastasis and minimal residual disease Patients who undergo radical rectal surgery still have a risk of recurrence, mainly because there may be a very small amount of hard-to-detect cancer cells remaining in their bodies. This condition is called minimal residual disease (MRD), which refers to a small portion of cancer cells that remain alive after surgery or adjuvant therapy and cannot be detected by conventional imaging or blood markers. They may remain in the surgical area, or spread to other sites to form micrometastases, and eventually gradually grow into detectable recurrent tumors (Negro et al., 2025). Some surviving cells have characteristics similar to stem cells and can evade clearance by the immune system, thereby remaining latent for a long time and causing recurrence (Kawashima et al., 2025). By detecting circulating tumor DNA (ctDNA) in the postoperative blood, MRD can be identified more sensitively. It can not only reflect in real time whether there are residual cells in the body, but also predict the recurrence risk more accurately (Kotani et al., 2023; Nakamura et al., 2024). Tumor micrometastasis is closely related to colorectal cancer. Even for patients with early-stage colorectal cancer, cancer cells may have already spread to other parts of the body. These cells may enter a "dormant" state, then become active again and keep growing, causing some patients to experience relapses within months or years after surgery. This process is not only influenced by the genetic or epigenetic characteristics of the tumor itself, but also related to the surrounding environment of the primary lesion and potential metastatic sites (Negro et al., 2025). The detection of MRD using ctDNA has changed our understanding of the recurrence mechanism. It can not only select patients with the highest risk of recurrence, but also detect problems in advance before symptoms occur, providing more time for early intervention. This new understanding has driven people to pay more attention to incorporating molecular monitoring into the management after colorectal cancer surgery. 2.2 The influence of clinicopathological features Clinicopathological features remain one of the fundamental bases for evaluating the risk of postoperative recurrence of colorectal cancer. Studies have shown that the higher the tumor stage, especially when T4 lesions and lymph node metastasis (N+) occur, the recurrence rate significantly increases (Huang et al., 2025; Takagi et al., 2025). Since stage T4 suggests deeper tumor invasion and lymph node metastasis indicates that cancer cells may have spread throughout the body, both are usually regarded as independent risk factors for recurrence (Ryu et al., 2023). Pathological factors such as lymphatic vessel or nerve invasion, poor tumor differentiation, and positive surgical margin are also associated with an increased risk of recurrence and are often included in the recurrence risk assessment model (Hwang et al., 2025). Molecular testing provides a new supplementary approach for assessing the risk of recurrence. Gene mutations such as APC, BRAF, and NRAS are closely related to recurrence time and overall survival. Among them, patients carrying BRAF or NRAS mutations often have poor therapeutic effects and a poor prognosis. APC mutations are more common in the population with early recurrence (Kasai et al., 2025). Among the commonly used molecular subtypes, the recurrence-free survival period of patients with CMS4 type is significantly shorter, suggesting that it
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