Management of Hepatocellular Carcinoma
Treatment Selection Based on BCLC Staging
Management of HCC is determined by the Barcelona Clinic Liver Cancer (BCLC) staging system, which integrates tumor characteristics (size, number, vascular invasion, metastases), liver function (Child-Pugh grade), and performance status (ECOG) to guide treatment allocation. 1
Very Early and Early Stage (BCLC 0 and A)
Surgical resection is the first-line treatment for patients with solitary tumors and well-preserved liver function, defined as normal bilirubin with hepatic venous pressure gradient ≤10 mmHg or platelet count ≥100,000. 1 Anatomical resections are recommended with expected perioperative mortality of 2-3% in cirrhotic patients. 1
Liver transplantation is the first-line option for patients meeting Milan criteria (single tumor <5 cm or ≤3 nodules ≤3 cm) who are not suitable for resection due to impaired liver function. 1, 2 Perioperative mortality is approximately 3% with one-year mortality ≤10%. 1 For waiting lists exceeding 6 months, neo-adjuvant locoregional therapy should be considered. 1
Radiofrequency ablation (RFA) or microwave ablation (MWA) is recommended for tumors ≤3 cm in very early HCC (BCLC 0). 1 For tumors in proximity to gallbladder, stomach, colon, or other viscera, percutaneous ethanol injection or surgical resection should be chosen instead. 1
Intermediate Stage (BCLC B)
Transarterial chemoembolization (TACE) is the treatment of choice for intermediate-stage HCC with multinodular tumors without vascular invasion or extrahepatic spread, particularly in Child-Pugh A patients. 1 TACE provides both tumor-feeding vessel embolization and chemotherapy infusion, improving overall survival by 20-60% at 2 years. 1 TACE can also be used for down-staging patients outside Milan criteria before liver transplantation. 1
Advanced Stage (BCLC C)
For first-line systemic therapy in advanced HCC with preserved liver function, atezolizumab plus bevacizumab is the preferred treatment, showing superiority to sorafenib in survival outcomes. 3
Lenvatinib is FDA-approved as first-line treatment for unresectable HCC, with recommended dosing of 12 mg for patients ≥60 kg or 8 mg for patients <60 kg, taken orally once daily until disease progression or unacceptable toxicity. 3, 4
Sorafenib remains a standard first-line option for patients with advanced HCC and well-preserved liver function, demonstrating survival benefit of approximately 2.8 months. 3
For second-line therapy:
- Regorafenib is recommended for patients who tolerated but progressed on sorafenib, with well-preserved liver function and good performance status. 3
- Cabozantinib can be considered for patients with progressive disease on one or two prior systemic therapies. 3
- Ramucirumab is indicated for HCC patients with AFP ≥400 ng/mL previously treated with sorafenib. 3
- Nivolumab in combination with ipilimumab is approved for patients previously treated with sorafenib, though this indication is under accelerated approval. 5
Terminal Stage (BCLC D)
Best supportive care is recommended for patients with end-stage liver function (Child-Pugh C) and poor performance status (ECOG 3-4), with expected survival of approximately 3 months. 1, 3
Critical Treatment Considerations
Neo-adjuvant or adjuvant therapies have not proven to improve outcomes in patients treated with resection or local ablation. 1 Traditional systemic chemotherapy containing anthracyclines, cisplatin, and 5-FU shows limited efficacy with only 10% response rate and no proven survival benefit. 3
Treatment selection must account for hepatic functional reserve using Child-Pugh classification, performance status, extent of disease, and presence of extrahepatic spread. 3, 2 For Child-Pugh B patients, carefully selected systemic therapy or clinical trials can be considered, while Child-Pugh C patients should receive best supportive care only. 3
Response assessment should be based on dynamic CT or MRI using modified RECIST criteria. 3 Tumor recurrence after curative treatment requires re-assessment by BCLC staging and re-treatment accordingly. 1