Cancer Genetics and Epigenetics, 2025, Vol.13, No.5, 236-244 http://medscipublisher.com/index.php/cge 237 microenvironment is conducive to formulating more appropriate individualized treatment plans, reducing the recurrence rate, and improving the survival level of liver cancer patients. 2 Clinical Characteristics of Postoperative Recurrence of Liver Cancer 2.1 Recurrence types: the difference between early recurrence and late recurrence Postoperative recurrence of hepatocellular carcinoma (HCC) is generally divided into early stage (within two years after surgery) and advanced stage (after two years after surgery), and the occurrence mechanisms of the two are different. Early recurrence is mostly caused by residual primary tumor or intrahepatic metastasis, while late recurrence is often associated with neoplasms in the context of chronic liver disease or liver cirrhosis (Hsiao et al., 2024). Early recurrence often shows stronger invasions, such as accompanied by vascular invasion or poor cell differentiation, and therefore the prognosis is usually worse than that of late recurrence (Kim et al., 2020; Wang et al., 2020; Lee et al., 2021). The forms of recurrence also vary. Early recurrence is often manifested as multiple lesions in the liver and may also spread to other areas of the liver. Late recurrence is more common in cases where there is only a single liver lesion. The main high-risk factors for early recurrence include: large tumor, microvascular invasion, and elevated alpha-fetoprotein (AFP) levels. Late recurrence is more associated with existing liver diseases, cirrhosis and active viral hepatitis (Yang et al., 2020; Abdelhamed and El-Kassas, 2023). Clearly distinguishing between these two types of recurrence is crucial for formulating subsequent follow-up and treatment plans. 2.2 Clinicopathological factors related to recurrence A number of clinical and pathological factors have been confirmed to be closely related to the postoperative recurrence of HCC. Large tumor size, numerous number, microvascular invasion, low differentiation and advanced stage all significantly increase the risk of recurrence (Lee et al., 2021). Especially microvascular invasion has been regarded as an independent predictor of overall recurrence, invasive recurrence and decreased survival rate (Wang et al., 2023; Fuster-Anglada et al., 2024; You et al., 2025). Other factors such as elevated AFP before surgery, incomplete tumor capsule, presence of satellite foci, and activity of hepatitis B or C virus will also further increase the possibility of recurrence (Kim et al., 2020; Wang et al., 2020; Hsiao et al., 2024). These factors not only affect the recurrence rate, but also determine the recurrence time and form - more aggressive characteristics often lead to earlier recurrence and extrahepatic metastasis (Straka et al., 2022; Abdelhamed and El-Kassas, 2023). 2.3 Clinical challenges of recurrence Postoperative recurrence of liver cancer has brought great difficulty to clinical treatment. The main reason is that recurrence will shorten the overall survival time of patients and limit treatment methods. Patients with early or invasive recurrence (especially extrahepatic or multifocal recurrence) usually have a significantly worse prognosis than those with late or intrahepatic recurrence (Kim et al., 2020). The 5-year survival rate decreased significantly after recurrence, indicating that effective risk stratification and early intervention are highly necessary (Fuster-Anglada et al., 2024; You et al., 2025). Due to the decline in liver function, it is often accompanied by other diseases and has a poor response to conventional treatments, making the treatment of recurrent liver cancer (HCC) more complicated. Different recurrence patterns also increase the difficulty of treatment: some patients are suitable for reoperation or local ablation, while some patients are more suitable for systemic treatment or palliative care to alleviate symptoms (Straka et al., 2022; Giuliani et al., 2024). These circumstances indicate that monitoring and treatment plans must be formulated based on the specific conditions of the patients in order to achieve better therapeutic effects among high-risk patients. 3 The Composition and Evolution of the Tumor Immune Microenvironment 3.1 The basic components of TIME The tumor immune microenvironment (TIME) is a very complex and constantly changing system, including
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