Preoperative prediction of microvascular invasion: new insights into personalized therapy for early-stage hepatocellular carcinoma

Abstract

Owing to advances in diagnosis and treatment methods over past decades, a growing number of early-stage hepatocellular carcinoma (HCC) diagnoses has enabled a greater of proportion of patients to receive curative treatment. However, a high risk of early recurrence and poor prognosis remain major challenges in HCC therapy. Microvascular invasion (MVI) has been demonstrated to be an essential independent predictor of early recurrence after curative therapy. Currently, biopsy is not generally recommended before treatment to evaluate MVI in HCC according clinical guidelines due to sampling error and the high risk of tumor cell seeding following biopsy. Therefore, the postoperative histopathological examination is recognized as the gold standard of MVI diagnosis, but this lagging indicator greatly impedes clinicians in selecting the optimal effective treatment for prognosis. As imaging can now noninvasively and completely assess the whole tumor and host situation, it is playing an increasingly important role in the preoperative assessment of MVI. Therefore, imaging criteria for MVI diagnosis would be highly desirable for optimizing individualized therapeutic decision-making and achieving a better prognosis. In this review, we summarize the emerging image characteristics of different imaging modalities for predicting MVI. We also discuss whether advances in imaging technique have generated evidence that could be practice-changing and whether advanced imaging techniques will revolutionize therapeutic decision-making of early-stage HCC.

Keywords: Microvascular invasion (MVI); clinical decision-making; early-stage hepatocellular carcinoma (early-stage HCC); imaging; preoperative diagnosis.

Figure 1

Multistep biological process of MVI and MVI-derived pathological changes via a variety of diagnostic methods. ① Carcinoma cells in HCC initially interact with the local microenvironment. ② A tiny fraction of cancer stem cells recruit a variety of stromal cells and inflammatory cells to create a reactive microenvironment and acquire the ability of the invasive phenotype via the upregulation of certain oncogenes, the inactivation of suppressor genes, and the imbalance of immune genes. ③ These cells respond to contextual signals that induce them to express invasiveness and metastatic dissemination. Subsequently, local invasive cells invade into the surrounding matrix and blood vessels. ④ MVI-related pathological changes and the manifestation of different preoperative imaging methods. ⑤ Postoperative histopathological examination remains the gold standard for clinical MVI diagnosis: (A) Chinese pathological diagnosis guidelines suggest that all kinds of liver cancer should be sampled based on the 7-point baseline sample collection protocol (a-g). MVI is a nest of malignant cells in microvessels only visible under a microscope. (B) Pathological grading of MVI according to Chinese pathological diagnosis guidelines. HCC, hepatocellular carcinomas; MVI, microvascular invasion; MR, magnetic resonance imaging; CT, computed tomography; PET, positron emission tomography; US, ultrasound.

Figure 2

Flowchart of the proposed update to the BCLC treatment option. This figure is based on the BCLC 2022 update classification and has been modified by adding the MVI status, which advises patients with BCLC 0 and A tumors and MVI to consider LT as first-line treatment. *, liver function defined by Child-Pugh score and class. HCC, hepatocellular carcinoma; AFP, alpha-fetoprotein; ALBI, albumin-bilirubin; MELD, model for end-stage liver disease; PS, performance status; MVI, microvascular invasion; LT, liver transplant; BCLC, Barcelona Clinic Liver Cancer.

Figure 3

Current surgical therapies and prognosis of early-stage HCC with MVI status, which according to the available scientific evidence, the tumor is a size ≥2 cm. MVI, microvascular invasion; LT, liver transplant; TACE, transcatheter arterial chemoembolization; 5y-DFS, 5-year disease-free survival; OS, overall survival.