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

Treatment Options for Hepatocellular Carcinoma (HCC)

The optimal treatment for hepatocellular carcinoma requires a multidisciplinary approach with treatment selection based on tumor stage, liver function, and patient performance status, with surgical resection, liver transplantation, and ablative therapies offering the best survival outcomes for early-stage disease. 1, 2

Staging and Assessment

• The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely validated system for HCC as it incorporates tumor burden, liver function, and performance status 2
• Initial assessment should include imaging (CT/MRI of abdomen), serum alpha-fetoprotein levels, and evaluation of liver function using Child-Pugh classification 1, 2
• Chest imaging and abdominal CT scan or MRI are essential to determine tumor extent and presence of extrahepatic disease 2

Treatment Options by Stage

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

• Surgical resection is the first-line treatment for patients with solitary tumors and well-preserved liver function, defined as normal bilirubin with either hepatic venous pressure gradient ≤10 mmHg or platelet count ≥100,000 1
• Anatomical resections are recommended when possible to improve outcomes 1
• Liver transplantation offers the best long-term outcome for patients with HCC in cirrhosis who meet Milan criteria (single tumor ≤5 cm; or 2-3 tumors, none >3 cm) with 3-year survival rates up to 88% 1
• Radiofrequency ablation (RFA) is recommended for selected patients with solitary HCC <5 cm or multiple tumors <3 cm who are not candidates for surgery 1, 3
• Percutaneous ethanol injection (PEI) can be considered for tumors <2 cm when RFA is not technically feasible 1

Intermediate Stage (BCLC B)

• Transarterial chemoembolization (TACE) is the standard of care for patients with multifocal HCC, preserved liver function, and no vascular invasion or extrahepatic spread 2
• TACE has demonstrated survival benefit in randomized controlled trials compared to no treatment 1
• Radioembolization with yttrium-90 microspheres is an alternative locoregional therapy being evaluated for intermediate HCC 1

Advanced Stage (BCLC C)

• Atezolizumab plus bevacizumab is the preferred first-line treatment for advanced HCC with preserved liver function, showing superiority to sorafenib alone 4
• Lenvatinib is FDA-approved as first-line treatment for unresectable HCC (12 mg for patients ≥60 kg or 8 mg for patients <60 kg) 4, 5
• Sorafenib remains a standard option for patients with advanced HCC and well-preserved liver function 4
• Second-line options after progression on first-line therapy include:
  • Regorafenib for patients who have tolerated but progressed on sorafenib 4
  • Cabozantinib for patients with progressive disease on prior systemic therapies 4
  • Ramucirumab for patients with alpha-fetoprotein (AFP) ≥400 ng/mL who have been previously treated with sorafenib 4

End-Stage (BCLC D)

• Best supportive care is recommended for patients with Child-Pugh C cirrhosis and HCC exceeding transplant criteria 2

Special Considerations

• Neoadjuvant locoregional therapy should be considered for patients listed for transplant to reduce waiting list dropout due to disease progression 2
• Traditional systemic chemotherapy containing anthracyclines, cisplatin, and 5-FU has shown limited efficacy with only about 10% response rate and no proven survival benefit 4
• The STORM trial showed that adjuvant sorafenib after resection or RFA did not improve recurrence-free survival or overall survival 1
• Response assessment should be based on dynamic CT or MRI studies using modified RECIST criteria 4

Prognosis

• Prognosis varies significantly based on BCLC stage, with 5-year survival rates between 50-75% for early stage disease 2
• For patients receiving curative treatments (resection, transplantation, ablation), 5-year survival rates of 60-80% can be achieved 1
• Recurrence remains a major challenge after curative treatments, necessitating regular surveillance with AFP determination and liver imaging every 3-6 months 3

Common Pitfalls and Caveats

• Delaying referral to a multidisciplinary team can limit treatment options and worsen outcomes 6, 7
• Overlooking the importance of liver function assessment when selecting treatment can lead to liver decompensation and treatment-related mortality 1, 2
• Failing to consider transplantation for early HCC in cirrhotic patients, even when resection is technically feasible 1
• Not recognizing that the fibrolamellar variant of HCC has different characteristics and management considerations, as it is not associated with cirrhosis or elevated AFP 1