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

Hepatocellular Carcinoma Treatment Guidelines

Treatment of hepatocellular carcinoma (HCC) should follow the Barcelona Clinic Liver Cancer (BCLC) staging system, which stratifies patients based on tumor characteristics, liver function, and performance status to determine optimal therapy for each stage. 1, 2

Staging and Assessment

The BCLC staging system categorizes patients into five groups:

• Very early stage (BCLC 0): Single tumor <2 cm, Child-Pugh A, no portal hypertension
• Early stage (BCLC A): Single tumor or up to 3 nodules ≤3 cm, Child-Pugh A-B
• Intermediate stage (BCLC B): Multinodular tumors, Child-Pugh A-B, no vascular invasion
• Advanced stage (BCLC C): Vascular invasion, extrahepatic spread, or cancer-related symptoms
• End-stage (BCLC D): Severe liver dysfunction, poor performance status

Treatment Algorithm by BCLC Stage

Very Early Stage (BCLC 0) and Early Stage (BCLC A)

1. Surgical Resection:

   • First choice for single tumors in patients without advanced fibrosis
   • Indicated when R0 resection is possible without causing postoperative liver failure
   • For cirrhotic patients: indicated with single lesion, good performance status, no significant portal hypertension 1
   • 5-year survival rates: 50-75% 1

2. Liver Transplantation:

   • Recommended for patients with solitary lesion <5 cm or up to 3 nodules ≤3 cm (Milan criteria) not suitable for resection 1
   • Particularly beneficial for patients with decompensated cirrhosis 2

3. Thermal Ablation:

   • First-line treatment for solitary tumors <2 cm in compensated cirrhosis 1
   • Alternative to resection for single nodules <2 cm or early stages not suitable for surgery 1
   • Radiofrequency ablation (RFA) provides better local control than percutaneous ethanol injection (PEI), especially for HCCs >2 cm 1
   • Maximum effectiveness: ≤5 tumors with total diameter ≤5 cm 1

Intermediate Stage (BCLC B)

Transarterial Treatments:

• Transarterial chemoembolization (TACE) is standard of care 1
• Best candidates: limited tumor burden (solitary <7 cm or <4 tumors), preserved liver function (Child A or B7 without ascites), good performance status 1
• TACE with drug-eluting beads recommended to minimize systemic side effects 1
• Conventional TACE, TACE with drug-eluting beads, and TAE are all considered standard options 1
• TACE should not be used in patients with decompensated liver disease, advanced kidney dysfunction, macrovascular invasion, or extrahepatic spread 1

Advanced Stage (BCLC C)

Systemic Therapy:

• First-line treatment: Atezolizumab plus bevacizumab is now the standard of care 1
  • Patients must be assessed for contraindications, including risk of variceal bleeding
  • Portal hypertension patients should have endoscopy within 6 months and adequately treated varices
• Alternative first-line options (for patients with contraindications to atezolizumab/bevacizumab):
  • Lenvatinib for unresectable HCC 3
  • Sorafenib for advanced HCC with well-preserved liver function 1

End-Stage (BCLC D)

• Symptomatic treatment only 1
• Best supportive care for patients with heavily impaired liver function or poor performance status 1

Special Considerations

Bridging Therapies for Transplant Candidates

• For anticipated waiting time >6 months for liver transplantation, consider resection, local ablation, or TACE to minimize tumor progression risk 1

Radioembolization

• Selective internal radiation therapy (SIRT) with Y-90 spheres may be considered for:
  • Patients with prior TACE failure
  • Excellent liver function
  • Macrovascular invasion without extrahepatic disease 1
  • Large solitary tumors 1

External Beam Radiotherapy

• Can be used for pain control in patients with bone metastases 1
• Stereotactic radiotherapy is an option for tumors not suitable for surgery or conventional ablation 1

Monitoring and Follow-up

• After curative treatments: Dynamic CT or MRI every 3 months for first 2 years, then every 6 months 1, 2
• Advanced HCC: Clinical evaluation and imaging every 2 months 1
• Response assessment based on dynamic CT or MRI using modified RECIST criteria 1
• Alpha-fetoprotein may be helpful but should not be the sole determinant for treatment decisions 1, 2

Important Caveats

• Neo-adjuvant or adjuvant therapies are not recommended after resection or local ablation 1
• TACE should not be combined with multikinase inhibitors 1
• Systemic chemotherapy, tamoxifen, immunotherapy, anti-androgen, or somatostatin analogues are not recommended for HCC management outside of approved regimens 1
• Up to one-third of patients may not fit standard guidelines due to advanced age, comorbidities, or tumor location, requiring individualized approaches 1