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

Treatment Options for Hepatocellular Carcinoma (HCC)

Treatment of hepatocellular carcinoma must be guided by tumor stage using the Barcelona Clinical Liver Cancer (BCLC) classification, with specific interventions for each stage to optimize survival outcomes. 1

Staging and Assessment

Before initiating treatment, proper staging is essential:

• Imaging: CT scan of abdomen and chest X-ray 1
• Laboratory: Serum AFP, liver function tests
• Assessment of liver function: Child-Pugh classification
• Performance status evaluation

The BCLC staging system divides patients into five prognostic categories, each with distinct treatment indications 1:

• Very early (BCLC 0): Single tumor <2cm
• Early (BCLC A): Single tumor <5cm or up to three nodules ≤3cm each
• Intermediate (BCLC B): Large/multinodular tumors
• Advanced (BCLC C): Vascular invasion and/or extrahepatic spread
• End-stage (BCLC D): Poor performance status with any tumor burden

Treatment Algorithm by Stage

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

1. Surgical Resection (Partial Hepatectomy)

   • First choice for patients without cirrhosis 1
   • For cirrhotic patients: consider if Child-Pugh A with normal bilirubin and no portal hypertension
   • 5-year survival rates: 50-75% 1

2. Liver Transplantation

   • Optimal for patients meeting Milan criteria (single tumor ≤5cm or up to three nodules ≤3cm) 1
   • Addresses both the tumor and underlying liver disease
   • Should be considered first for unresectable tumors 1

3. Local Ablation Techniques

   • Radiofrequency ablation (RFA): For tumors <5cm and/or fewer than four in number 1
   • Percutaneous ethanol injection: For patients with fewer than three or four tumor nodules, maximum 5cm 1
   • Alternative when surgery is not feasible

Intermediate Stage (BCLC B)

1. Transarterial Chemoembolization (TACE)
   • Standard of care for multinodular HCC with adequate liver function 1
   • Provides survival benefit of 16-22 months 1
   • Best for patients with adequate hepatic functional reserve

Advanced Stage (BCLC C)

1. Systemic Therapy

   • Sorafenib: First-line treatment for advanced HCC 1

     • Extends survival by approximately 2.8 months 1
     • Response rate of 8% and disease control in 41% of patients 1

   • Lenvatinib: FDA-approved first-line treatment for unresectable HCC 2

     • Alternative to sorafenib

2. Clinical Trials

   • Consider enrollment for patients with good performance status

End-Stage (BCLC D)

1. Best Supportive Care
   • Focus on symptom management
   • Child-Pugh C patients should receive only supportive care 1

Special Considerations

Bridging Therapies

• Local ablation or TACE can be used as bridging therapy for patients awaiting liver transplantation 3

Treatment Beyond Guidelines

• Up to one-third of patients may not fit recommendations due to advanced age, comorbidities, or tumor location 1
• Multimodal treatment approaches may be necessary for patients who don't achieve complete response with a single therapy 1

Recurrence Management

• HCC recurrence is a major obstacle to successful treatment 3
• Regular follow-up with AFP determination and liver imaging every 3-6 months for at least 2 years after curative resection 1

Common Pitfalls and Caveats

1. Delayed Diagnosis

   • HCC is often asymptomatic in early stages, leading to late diagnosis 4
   • Regular surveillance with ultrasound and AFP in high-risk patients is crucial

2. Treatment Selection Errors

   • Failure to properly assess liver function can lead to inappropriate treatment selection
   • Child-Pugh score and MELD score are essential for transplant candidates 1

3. Resistance to Therapy

   • HCC is markedly resistant to conventional chemo- and radiotherapy 4
   • Systemic therapies often provide only modest survival benefits and patients may develop resistance within 6 months 5

4. Overlooking Underlying Liver Disease

   • Treatment must address both the tumor and the underlying liver disease
   • Consider antiviral therapy for patients with hepatitis B or C 1

The complexity of HCC requires a stage-based approach to therapy that considers tumor burden, liver function, and patient performance status. While guidelines provide a framework, treatment decisions must sometimes extend beyond these recommendations to achieve optimal outcomes for individual patients.