What are the treatment options for hepatocellular carcinoma (HCC)?

Treatment Options for Hepatocellular Carcinoma (HCC)

For patients with hepatocellular carcinoma, treatment should be based on the Barcelona Clinic Liver Cancer (BCLC) staging system, with surgical resection, liver transplantation, ablation, transarterial therapies, or systemic therapy selected according to tumor characteristics, liver function, and patient performance status. 1

Staging and Assessment

The management of HCC requires proper staging using:

• Barcelona Clinic Liver Cancer (BCLC) staging system - most widely recommended framework for treatment allocation 1
• Child-Pugh classification - to assess liver function
• Performance status evaluation
• Assessment for portal hypertension

Treatment Algorithm by Disease Stage

Early Stage HCC (BCLC 0-A)

• Very early (BCLC 0): Single tumor <2 cm, Child-Pugh A, no portal hypertension

  • First choice: Surgical resection
  • 5-year survival rates: 50-75% 1

• Early (BCLC A): Single tumor or up to 3 nodules ≤3 cm, Child-Pugh A-B

  • For Child-Pugh A without portal hypertension: Surgical resection 2
  • For Child-Pugh B/C or with portal hypertension: Liver transplantation (if within Milan criteria) 2, 1
  • Alternative for non-surgical candidates: Radiofrequency ablation (RFA) or percutaneous techniques 2, 1
  • 5-year survival with transplantation: >75% 1

Intermediate Stage HCC (BCLC B)

• Multinodular tumors, Child-Pugh A/B, no vascular invasion or extrahepatic spread
  • Standard treatment: Transarterial chemoembolization (TACE) 2, 1
  • Expected survival benefit: 16-22 months 1

Advanced Stage HCC (BCLC C)

• Vascular invasion, extrahepatic spread, or cancer-related symptoms
  • First-line systemic therapy:
    • Lenvatinib (12 mg for patients ≥60 kg or 8 mg for patients <60 kg) 3
    • Atezolizumab plus bevacizumab 1, 4
  • Second-line therapy: Regorafenib after sorafenib failure 5

End-Stage HCC (BCLC D)

• Severe liver dysfunction, poor performance status
  • Recommended approach: Best supportive care 5
  • Median survival: approximately 6 months 5

Specific Treatment Considerations

Surgical Resection

• Indications: Unilobar tumors without vascular invasion or metastases in patients with preserved liver function (Child-Pugh A) 2
• Contraindications: Significant portal hypertension, inadequate future liver remnant, Child-Pugh C 2
• Preoperative considerations:
  • Portal vein embolization (PVE) may be used to induce hypertrophy of the remnant liver 2
  • Anatomic resection is preferred for oncological outcomes 2
• Recurrence risk: 50-70% at 5 years 2

Liver Transplantation

• Indications: Tumors within Milan criteria (single tumor ≤5 cm or up to 3 nodules ≤3 cm) in patients with decompensated cirrhosis 2, 1
• Outcomes: 1-, 3-, and 5-year survival rates of 85%, 75%, and 70%, respectively 2
• Advantage: Addresses both the tumor and underlying liver disease 1

Ablative Therapies

• Radiofrequency ablation (RFA):
  • Suitable for tumors <5 cm and/or fewer than four in number 1
  • Response rate: 70-80% 1
  • Better local control than percutaneous ethanol injection (PEI) for tumors >2 cm 1

Transarterial Therapies

• Transarterial chemoembolization (TACE):
  • Standard for multinodular tumors without vascular invasion or extrahepatic spread 1
  • Not recommended as primary treatment for early-stage HCC 2

Systemic Therapy

• Lenvatinib:

  • FDA-approved for first-line treatment of unresectable HCC 3
  • Dosage: 12 mg for patients ≥60 kg or 8 mg for patients <60 kg, taken orally once daily 3
  • Continue until disease progression or unacceptable toxicity 3

• Immunotherapy:

  • Emerging option for advanced HCC 4, 6
  • Immune checkpoint inhibitor (ICI)-based therapy is increasingly preferred for advanced disease 6

Surveillance After Treatment

• After curative treatments: Dynamic CT or MRI every 3 months for the first 2 years, then every 6 months thereafter 1
• For advanced HCC: Clinical evaluation and imaging every 2 months 1

Pitfalls and Caveats

• HCC is often diagnosed at advanced stages when curative options are no longer viable 7
• Patients with similar disease phenotypes may have different molecular etiologies affecting treatment response 7
• Conventional chemotherapy and radiotherapy have limited efficacy in HCC 4
• Systemic therapies provide only modest survival benefits (approximately 3 months) and often lead to resistance 7
• Multidisciplinary care is essential for optimal treatment decisions and improved survival 5, 6