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Published on: March 10, 2023
Surgery for Hepatocellular Carcinoma With Macroscopic Vascular Invasion in the Era of Modern Molecular Therapy
Kensuke Yamamura1, Toru Beppu2, Tatsunori Miyata3
1Department of Gastroenterology, Yamaga City Medical Center, Yamaga, Japan.
Abstract:
It has been reported that patients with macroscopic vascular invasion accompanying hepatocellular carcinoma have a poor prognosis. Modern molecular therapy with multitargeted tyrosine kinase inhibitors and immune checkpoint inhibitors has shown promising results in patients with metastatic hepatocellular carcinoma; however, molecular therapy is limited to patients with Child-Pugh class A disease. This review summarizes the present status of surgical therapies, including conversion hepatectomy, for patients with MVI in the developing era of novel molecular therapy. Phase III studies showed patients with macroscopic vascular invasion had significant survival benefits from sorafenib [hazard ratio (HR)=0.68] and regorafenib (HR=0.67) versus placebo, and nivolumab (HR=0.74) versus sorafenib. Lenvatinib and atezolizumab plus bevacizumab showed marginal effects. It is currently widely assumed that molecular therapy alone will not cure the disease but that additional conversion hepatectomy will be required. A response other than progressive disease is essential but a pathological complete response is not always required. A significant randomized controlled trial has already started in China to assess the necessity for conversion hepatectomy after effective atezolizumab plus bevacizumab treatment, and the results are still awaited. According to Japanese national data, upfront hepatectomy can be recommended for patients with initially resectable disease and macroscopic vascular invasion other than for those with tumors in the main portal vein and the inferior vena cava. In addition, adequate adjuvant therapies with hepatic arterial chemotherapy and transarterial chemoembolization may be beneficial but an effective adjuvant molecular therapy is currently unavailable. In conclusion, novel molecular therapies with higher response rates customized to the oncologic characteristics of each hepatocellular carcinoma with macroscopic vascular invasion are needed to increase the likelihood of conversion surgery and improve long-term outcomes.
Insights
For hepatocellular carcinoma with vascular invasion, molecular therapies show survival benefits but often require conversion hepatectomy. New therapies are needed to improve surgical success and long-term outcomes.
Area of Science:
- Hepatobiliary surgery
- Medical oncology
- Translational research
Background:
- Macroscopic vascular invasion (MVI) in hepatocellular carcinoma (HCC) indicates a poor prognosis.
- Current molecular therapies (tyrosine kinase inhibitors, immune checkpoint inhibitors) show promise for metastatic HCC but are limited to Child-Pugh class A patients.
- Surgical options, including conversion hepatectomy, are crucial for managing HCC with MVI.
Purpose of the Study:
- To review the current status of surgical therapies for HCC with MVI in the context of emerging molecular treatments.
- To evaluate the efficacy of existing molecular therapies and their role in facilitating conversion hepatectomy.
- To identify future directions for improving outcomes in HCC with MVI.
Main Methods:
- Review of Phase III clinical trial data for molecular therapies (sorafenib, regorafenib, nivolumab, lenvatinib, atezolizumab plus bevacizumab) in HCC with MVI.
- Analysis of national data regarding upfront hepatectomy and adjuvant therapies in Japan.
- Discussion of ongoing randomized controlled trials assessing conversion hepatectomy necessity.
Main Results:
- Sorafenib, regorafenib, and nivolumab demonstrated significant survival benefits in HCC with MVI.
- Lenvatinib and atezolizumab plus bevacizumab showed marginal effects.
- Upfront hepatectomy is recommended for resectable HCC with MVI, excluding main portal vein or inferior vena cava involvement.
- Adjuvant therapies like hepatic arterial chemotherapy and transarterial chemoembolization may be beneficial, but effective adjuvant molecular therapy is lacking.
Conclusions:
- Molecular therapy alone is unlikely to cure HCC with MVI; conversion hepatectomy is often necessary.
- Achieving a response other than progressive disease is crucial for successful conversion surgery.
- Development of novel molecular therapies with higher response rates tailored to HCC with MVI is essential to increase conversion surgery rates and improve long-term survival.