What is the role of hepatic artery embolization (HAE) in the management of liver cancer?

Hepatic Artery Embolization in Liver Cancer Management

Hepatic artery embolization (HAE) is a standard first-line treatment for intermediate-stage hepatocellular carcinoma (HCC) in patients with preserved liver function who are not candidates for curative therapies such as resection, transplantation, or ablation. 1, 2

Types of Hepatic Artery Embolization

• Bland Embolization (TAE): Uses embolic particles alone to block arterial blood flow to tumors, causing ischemia and tumor necrosis 1, 2
• Transarterial Chemoembolization (TACE): Combines chemotherapy with embolic agents, available in two forms:
  • Conventional TACE (cTACE): Uses a mixture of chemotherapy drugs with lipiodol followed by embolic particles 2
  • Drug-eluting bead TACE (DEB-TACE): Uses microspheres loaded with chemotherapeutic agents that simultaneously deliver the drug and cause embolization 2, 3
• Transarterial Radioembolization (TARE): Uses microspheres loaded with radioactive compounds (typically yttrium-90) 1

Patient Selection Criteria

Ideal Candidates for HAE/TACE:

• Patients with intermediate-stage HCC (BCLC stage B) 1
• Preserved liver function (Child-Pugh A or B7 without ascites) 1, 2
• Good performance status (ECOG <2) 1
• Limited tumor burden (solitary nodule <7 cm or fewer than four tumors) 1
• Patients with unresectable/inoperable disease not amenable to ablation therapy 1
• Absence of extrahepatic disease 1

TARE Candidates:

• Patients with large solitary tumors 1
• Patients with tumors associated with local macrovascular invasion when systemic therapy tolerance is a concern 1
• Can be safely used in portal vein thrombosis, unlike TACE 1

Contraindications

Absolute Contraindications:

• Decompensated liver disease (Child-Pugh C or decompensated Child-Pugh B) 1
• Advanced liver dysfunction 2
• Severely reduced portal vein flow 1
• Obstructive jaundice 2
• Poor performance status (ECOG ≥2) 1

Relative Contraindications:

• Macroscopic vascular invasion (for TACE/TAE) 1
• Extrahepatic spread (case-specific) 1
• Extensive tumor with massive replacement of both entire lobes 1
• Untreatable arteriovenous fistula 1
• Bilio-enteric anastomosis or biliary stents 1
• Creatinine clearance <30 ml/min 1

Effectiveness and Outcomes

• HAE has shown survival benefits compared to supportive care alone, with 1-year survival rates of 53% and 3-year survival rates of 15% 4
• Smaller tumors (<2 cm) have significantly better outcomes, with 100% 3-year survival rates compared to 0% for tumors >5 cm 4
• TACE extends median survival for intermediate HCC from approximately 16 months to about 20 months 2
• No significant difference in response rates has been demonstrated between chemoembolization and bland embolization in randomized trials (5.9% vs. 6.0%) 5
• TARE has shown longer time to disease progression compared to TACE, but with minimal or no impact on overall survival 1

Treatment Protocol

• Pre-procedure evaluation requires careful assessment of arterial anatomy to prevent non-target embolization 1
• For tumors >5 cm, arterial embolic approaches are recommended 1
• For tumors 3-5 cm, combination therapy with ablation and arterial embolization can be considered 1
• TACE can be performed either at regular intervals or on-demand based on tumor response 1
• On-demand TACE (performed based on tumor response and patient tolerance) may reduce liver damage and complications 1
• Post-procedure imaging (CT or MRI) is essential to evaluate tumor response using modified RECIST criteria 2

Special Considerations

• TACE can be used for downstaging before liver transplantation in patients outside the Milan criteria 1
• For patients with portal vein thrombosis, TARE is safer than TACE, which could increase the risk of liver failure 1
• Recent studies show TACE may still provide survival benefit over conservative therapy when portal vein thrombus is present, though the benefit is less pronounced with advanced vascular invasion 1
• The combination of TACE with systemic agents such as sorafenib is not recommended in standard clinical practice 1
• TACE failure or refractoriness (requiring discontinuation) is indicated by persistent viable lesions after consecutive treatments, new intrahepatic lesions, continuous elevation of tumor markers, or appearance of vascular invasion or extrahepatic spread 1

Common Complications

• Post-embolization syndrome (fever, abdominal pain) is the most common side effect 1, 6
• Major complications include portal vein thrombosis, hepatic abscess, and liver failure 6
• Treatment-related mortality rate is approximately 4.1% 6
• Risk of liver failure is higher when treating patients with macroscopic portal vein invasion 1

Hepatic artery embolization remains a cornerstone in the management of unresectable HCC, with treatment selection requiring careful consideration of tumor characteristics, liver function, and patient performance status to maximize benefits while minimizing complications.