Treatment of Hepatocellular Carcinoma (HCC)
The optimal treatment for hepatocellular carcinoma is based on the Barcelona Clinic Liver Cancer (BCLC) staging system, with surgical resection, liver transplantation, or ablation for early stages; transarterial chemoembolization for intermediate stages; and systemic therapy with atezolizumab plus bevacizumab as first-line treatment for advanced disease. 1
BCLC Staging and Treatment Algorithm
The BCLC staging system categorizes patients into five groups based on tumor characteristics, liver function, and performance status:
| Stage | Description | Primary Treatment |
|---|---|---|
| Very early (BCLC 0) | Single tumor <2 cm, Child-Pugh A | Ablation/Resection |
| Early (BCLC A) | Single or ≤3 nodules ≤3 cm | Resection/Transplantation/Ablation |
| Intermediate (BCLC B) | Multinodular, no vascular invasion | TACE |
| Advanced (BCLC C) | Vascular invasion or extrahepatic spread | Systemic therapy |
| End-stage (BCLC D) | Severe liver dysfunction | Supportive care |
Curative Treatment Options
1. Surgical Resection
- Indication: First choice for single tumors in patients without advanced fibrosis 1
- Eligibility criteria:
- R0 resection possible without causing postoperative liver failure
- Single lesion
- Good performance status
- No significant portal hypertension
- Outcomes: 5-year survival rate of 50-75% 1
- Limitations: High recurrence risk (50-70% at 5 years) 1
2. Liver Transplantation
- Indication: Patients with tumors within Milan criteria (solitary lesion <5 cm or up to 3 nodules ≤3 cm) 1
- Best candidates: Patients with decompensated cirrhosis and early-stage HCC 1
- Outcomes: 5-year survival rate of 70% 1
- Advantage: Eliminates underlying cirrhosis that puts the liver at risk for subsequent new primary tumors 2
- Limitation: Limited donor organ availability 2
3. Thermal Ablation
- Indication: First-line treatment for solitary tumors <2 cm in compensated cirrhosis 1
- Best candidates: Patients with ≤5 tumors with total diameter ≤5 cm 1
- Techniques: Radiofrequency ablation (RFA) provides better local control than percutaneous ethanol injection (PEI) 1
Locoregional Treatments
Transarterial Chemoembolization (TACE)
- Indication: Standard of care for intermediate-stage HCC (BCLC B) 1
- Best candidates: Patients with solitary tumor <7 cm or <4 tumors, Child A or B7 without ascites 1
- Options: Conventional TACE, TACE with drug-eluting beads, and transarterial embolization (TAE) 1
- Outcomes: Improves survival from 16 to 20 months in well-compensated cirrhosis 2
Systemic Therapy for Advanced HCC
First-line Treatment
Atezolizumab plus bevacizumab
- Current standard first-line treatment for advanced HCC 1
- Requires assessment for contraindications and portal hypertension management
Lenvatinib
Sorafenib
Second-line Treatment
- Regorafenib: Indicated for HCC patients previously treated with sorafenib 4
Special Considerations
Treatment Selection Pitfalls
- Up to one-third of patients with early-stage tumors may be unfit for radical therapy due to advanced age, comorbidities, or strategic tumor location 2, 1
- Patients with moderate portal hypertension and certain BCLC B patients might still benefit from hepatic resection if 50% survival at 5 years is achievable 2
Response Assessment
- Dynamic CT or MRI every 3 months for the first 2 years after curative treatments 1
- Modified RECIST criteria should be used for response assessment 1
- Alpha-fetoprotein (AFP) is helpful but should not be the sole determinant for treatment decisions 1
Multidisciplinary Approach
- Comprehensive staging is essential before initiating treatment, including complete imaging, liver function assessment, performance status evaluation, and assessment for portal hypertension 1
- Regular monitoring of liver function during treatment is crucial to minimize hepatotoxicity 1