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

Treatment Options for Hepatocellular Carcinoma

For early-stage HCC, surgical resection is the first-line treatment for patients with solitary tumors, Child-Pugh class A liver function, and no clinically significant portal hypertension, achieving 5-year survival rates of 50-68%. 1, 2

Treatment Selection Algorithm Based on Clinical Presentation

For Non-Cirrhotic Liver

• Surgical resection by partial hepatectomy is the definitive standard treatment regardless of tumor size, provided R0-resection can be achieved without causing postoperative liver failure, with perioperative mortality of 2-3%. 3, 1, 2

For Cirrhotic Liver with Preserved Function (Child-Pugh Class A)

Unifocal HCC <2 cm:

• Thermal ablation (radiofrequency ablation or microwave ablation) is recommended as first-line treatment alongside resection as equally valid options, with the choice depending on tumor location and extent of portal hypertension. 1, 2
• RFA provides superior local control compared to percutaneous ethanol injection, especially for tumors >2 cm. 1

Unifocal HCC 2-5 cm:

• Surgical resection is the preferred treatment when all of the following criteria are met: single lesion, 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
• If resection is not feasible due to tumor location or inadequate future liver remnant, RFA or MWA should be performed for tumors ≤3 cm. 1
• Portal vein embolization can be utilized to induce hypertrophy of the remnant liver when future liver remnant is inadequate. 3

Multifocal HCC within Milan criteria (≤3 nodules ≤3 cm):

• Liver transplantation is the recommended first-line treatment, achieving 1-, 3-, and 5-year survival rates of 85%, 75%, and 70% respectively. 3, 1, 2
• Surgical resection is recommended for peripheral tumors, hepatic transplantation for central tumors, and percutaneous techniques for microtumors. 3

For Cirrhotic Liver with Moderate Dysfunction (Child-Pugh Class B)

Unifocal HCC <5 cm:

• Hepatic transplantation is the preferred option, particularly for patients with decompensated cirrhosis and tumors within Milan criteria. 3
• For small lesions, percutaneous techniques are recommended. 3
• Chemo-embolization or radioactive lipiodol can be considered as alternatives. 3

Multifocal HCC (≤3 lesions <5 cm):

• Surgical resection, transplantation, and percutaneous procedures can be considered. 3
• For other presentations, chemo-embolization or radioactive lipiodol injections are options. 3

For Cirrhotic Liver with Severe Dysfunction (Child-Pugh Class C)

• Do not offer resection to Child-Pugh class C patients, as perioperative mortality risk is prohibitive (30-50%). 3, 2
• Hepatic transplantation is the only potentially curative option for highly selected patients with tumor burden within Milan criteria. 3, 4
• Hormone therapy or best supportive care are palliative options. 3

Advanced and Metastatic HCC

Unresectable or Metastatic HCC without prior systemic therapy:

• Atezolizumab 840 mg IV every 2 weeks (or 1200 mg every 3 weeks or 1680 mg every 4 weeks) in combination with bevacizumab 15 mg/kg every 3 weeks is the first-line treatment, administered until disease progression or unacceptable toxicity. 5
• Atezolizumab should be administered prior to bevacizumab when given on the same day. 5

Advanced HCC (BCLC Stage C with vascular invasion/extrahepatic spread):

• Sorafenib 400 mg orally twice daily without food is indicated for unresectable HCC, demonstrating survival benefit of 10.7 vs 7.9 months in the SHARP trial. 4, 6
• Sorafenib should be taken at least 1 hour before or 2 hours after a meal until the patient is no longer clinically benefiting or until unacceptable toxicity. 6

Intermediate Stage HCC (BCLC Stage B - multinodular, no vascular invasion):

• Transarterial chemoembolization (TACE) is the standard of care, with survival benefit of 16 to 22 months. 4

Metastatic HCC:

• There is no standard treatment. 3
• Chemotherapy, high-dose interferon, hormone therapy, surgical excision (if feasible), or symptomatic treatment can be considered. 3

Critical Contraindications and Pitfalls

• Do not proceed with transplantation in patients with macrovascular invasion or extrahepatic disease, as outcomes are universally poor. 2
• Clinically significant portal hypertension is a contraindication to resection, with surrogate markers including esophageal varices, ascites, and portal hypertensive gastropathy. 3, 2
• The minimum safe future liver remnant ranges from 20% for normal liver, 30% for chronic liver disease, and 40% for cirrhotic liver. 3, 4

Adjuvant and Bridging Therapies

• Atezolizumab plus bevacizumab improves recurrence-free survival after resection, though longer-term follow-up data are still needed. 2
• Patients listed for transplant should receive locoregional therapy (TACE or RFA) while waiting if technically feasible, reducing waiting list dropout from disease progression. 2
• Antiviral therapy is important for patients with HBV or HCV-related HCC to reduce risk of postoperative decompensation and prevent late recurrence from second primary tumors. 4

Follow-Up Protocol

• Patients undergoing curative resection should be followed every 3-6 months with AFP determination and liver imaging for at least 2 years, as curative therapy can still be offered at relapse. 1
• Response assessment should be based on dynamic CT or MRI using modified RECIST criteria. 1
• The absence of contrast uptake within the tumor reflects tumor necrosis, while persistence of contrast uptake indicates treatment failure. 3