What are the treatment options for Hepatocellular Carcinoma (HCC)?

Treatment of Hepatocellular Carcinoma

Treatment selection for HCC depends primarily on tumor stage, liver function (Child-Pugh class), and presence of portal hypertension, with surgical resection, liver transplantation, and local ablation offering curative potential for early-stage disease, while systemic therapies are reserved for advanced stages. 1, 2

Curative Treatment Options for Early-Stage HCC

Surgical Resection

• Resection is the first-line treatment for patients with non-cirrhotic livers regardless of tumor size, achieving 5-year survival rates of 50-68% in experienced centers. 3, 1, 2
• For cirrhotic patients, resection requires Child-Pugh class A liver function, absence of clinically significant portal hypertension (no varices, ascites, or portal hypertensive gastropathy), adequate future liver remnant (≥20-40% of total liver volume), and good performance status. 3, 1, 2
• Child-Pugh class C patients should never undergo resection due to prohibitive mortality risk from liver failure. 3, 1, 2
• Perioperative mortality has decreased to nearly 0% with improved surgical techniques and patient selection, with major complication rates around 3%. 3
• Laparoscopic resection should be offered when tumor location is suitable and surgeon expertise is available, providing reduced morbidity while maintaining oncological outcomes. 1

Liver Transplantation

• Transplantation is first-line treatment for patients meeting Milan criteria (solitary tumor ≤5 cm or 2-3 nodules ≤3 cm) who have decompensated cirrhosis. 3, 1, 2
• Living donor liver transplantation achieves 1-, 3-, and 5-year survival rates of 85%, 75%, and 70%, respectively. 3, 1, 2
• Transplantation eliminates both the tumor and the underlying cirrhotic liver that predisposes to new primary tumors. 3
• Patients listed for transplant should receive locoregional therapy while waiting if technically feasible to reduce dropout from disease progression. 1
• Macrovascular invasion or extrahepatic disease are absolute contraindications to transplantation due to universally poor outcomes. 1

Local Ablation Therapy

• For solitary HCC <2 cm, thermal ablation (radiofrequency or microwave) is recommended as first-line treatment alongside resection as equally valid options. 1, 2
• Radiofrequency ablation (RFA) or microwave ablation (MWA) is indicated for tumors ≤3 cm in patients not suitable for resection. 2
• RFA provides superior local control compared to percutaneous ethanol injection, especially for tumors >2 cm. 2
• The choice between ablation and resection depends on tumor location and extent of portal hypertension. 1

Treatment for Intermediate-Stage HCC

Transarterial Chemoembolization (TACE)

• TACE is the standard of care for multifocal HCC (intermediate stage BCLC B) with preserved liver function and no vascular invasion or extrahepatic spread, extending median survival from 16 to 22 months. 3, 4
• Repeated TACE treatments are advocated for patients with large tumor burden who are not surgical candidates. 3

Systemic Therapy for Advanced HCC

First-Line Systemic Therapy

• Atezolizumab plus bevacizumab is the preferred first-line immune checkpoint inhibitor-based regimen for advanced HCC (BCLC C). 4
• Atezolizumab plus bevacizumab also improves recurrence-free survival after resection, though longer-term follow-up data are still needed. 1
• Lenvatinib is FDA-approved for first-line treatment of unresectable HCC, with dosing of 12 mg for patients ≥60 kg or 8 mg for patients <60 kg orally once daily. 5
• Sorafenib remains an alternative first-line option, having extended survival by 2.8 months in phase III trials. 4

Second-Line Systemic Therapy

• Ramucirumab as a single agent is FDA-approved for HCC patients with AFP ≥400 ng/mL who have been treated with sorafenib. 6

Treatment Selection Algorithm

Step 1: Assess liver function and tumor characteristics

• Determine Child-Pugh class (bilirubin, albumin, prothrombin time, ascites, encephalopathy). 3, 1
• Evaluate for clinically significant portal hypertension (varices, ascites, portal hypertensive gastropathy). 3, 1
• Measure tumor size, number, and assess for vascular invasion or extrahepatic disease. 3

Step 2: Apply treatment based on clinical scenario

• Non-cirrhotic liver with resectable tumor: Proceed with surgical resection. 1, 2
• Child-Pugh A, single tumor, no portal hypertension, adequate future liver remnant: Proceed with surgical resection. 1, 2
• Child-Pugh A-B with decompensated cirrhosis, tumor within Milan criteria: Prioritize liver transplantation. 1, 2
• Solitary tumor <2 cm or tumor ≤3 cm not suitable for resection: Perform RFA or MWA. 1, 2
• Multifocal HCC with preserved liver function, no vascular invasion: Perform TACE. 3, 4
• Advanced HCC with vascular invasion or extrahepatic disease: Initiate atezolizumab plus bevacizumab or lenvatinib. 4, 5

Follow-Up Protocol

• After curative resection, perform AFP determination and liver imaging (dynamic CT or MRI) every 3-6 months for at least 2 years, as curative therapy can still be offered at relapse. 2, 4
• Response assessment should use modified RECIST criteria on dynamic CT or MRI. 2, 4

Critical Pitfalls to Avoid

• Never offer resection to Child-Pugh class C patients due to prohibitive mortality from liver failure. 3, 1, 2
• Do not proceed with transplantation in patients with macrovascular invasion or extrahepatic disease. 1
• Do not rely solely on tumor size for treatment decisions; vascular invasion indicates aggressive biology requiring systemic therapy rather than locoregional treatment. 4
• Recognize that up to one-third of patients do not fit standard guideline recommendations due to advanced age, comorbidities, or strategic tumor location, requiring individualized approaches beyond guidelines. 3