What are the treatment options for a patient with primary liver cancer (hepatocellular carcinoma) and a history of liver disease?

Treatment of Primary Liver Cancer (Hepatocellular Carcinoma)

Treatment selection for HCC depends on tumor stage using the BCLC staging system, which integrates tumor burden, liver function (Child-Pugh class), portal hypertension status, and performance status to guide therapy. 1

Initial Assessment and Staging

All patients with suspected HCC must undergo:

• Triphasic CT or MRI of the abdomen to characterize lesions and assess vascular invasion 2
• Child-Pugh classification to determine hepatic reserve 1
• Portal hypertension assessment via hepatic venous pressure gradient (HVPG) if resection is considered; HVPG >10 mmHg contraindicates major resection 3
• Performance status evaluation using WHO or ECOG criteria 1
• AFP measurement and chest imaging to exclude extrahepatic spread 1

Every patient must be evaluated by a multidisciplinary team including hepatologists, surgeons, interventional radiologists, and oncologists before treatment decisions are made. 1

Treatment Algorithm by Stage

Very Early/Early Stage HCC (Single tumor or up to 3 nodules ≤3 cm, Child-Pugh A-B, no vascular invasion)

For patients with decompensated cirrhosis (Child-Pugh B) or early multifocal disease within Milan criteria (single lesion ≤5 cm or up to 3 lesions ≤3 cm), liver transplantation is the optimal treatment, achieving 3-year survival up to 88%. 1, 4

For patients with solitary tumors and well-compensated cirrhosis (Child-Pugh A, normal bilirubin, HVPG ≤10 mmHg or platelet count ≥100,000), surgical resection is first-line treatment with 5-year survival of 60-80%. 1, 3

• Anatomical resections are preferred over non-anatomical resections 1
• Expected perioperative mortality should be 2-3% in cirrhotic patients 1, 3
• Absolute contraindications to resection: Child-Pugh C cirrhosis, Child-Pugh B with major resection planned, clinically significant portal hypertension with HVPG >10 mmHg 3

For tumors <2 cm in compensated cirrhosis, radiofrequency ablation and resection are equally effective options. 3

For tumors 2-5 cm, percutaneous ablation (radiofrequency or microwave) achieves 5-year survival of 50-75% in well-selected candidates. 1

Intermediate Stage HCC (Large/multifocal tumors, Child-Pugh A-B, no symptoms, no vascular invasion/extrahepatic spread)

Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage HCC, with 3-year survival reaching 50%. 1

• TACE should be repeated if initial response is inadequate 1
• Patients not responding after two TACE cycles should be switched to sorafenib 1

Advanced Stage HCC (Symptomatic disease, vascular invasion, or extrahepatic spread)

For unresectable HCC with preserved liver function (Child-Pugh A), lenvatinib is FDA-approved first-line systemic therapy. 5

• Lenvatinib dosing: 12 mg daily for patients ≥60 kg or 8 mg daily for patients <60 kg 5
• Median survival with first-line systemic therapy is approximately 12 months (50% survival at 1 year) 1

Sorafenib remains an alternative first-line option for advanced HCC but is inappropriate for potentially resectable or transplantable disease. 4

End-Stage HCC (Child-Pugh C, WHO performance status ≥2, extensive tumor burden)

Only supportive/palliative care should be offered, as median survival is less than 3 months and active treatments provide no benefit. 1

Special Considerations for Transplant Candidates

If transplant waiting time exceeds 6 months, bridging TACE should be performed to prevent tumor progression and dropout from the transplant list. 4

While awaiting transplant, patients require:

• Serial imaging every 3 months 4
• AFP monitoring 4
• MELD score calculation 1, 4
• Antiviral therapy for hepatitis B to prevent graft reinfection 4

Expanded UCSF criteria (single tumor ≤6.5 cm, 2-3 tumors with none >4.5 cm, or total tumor diameter ≤8 cm without vascular invasion) may be considered for transplantation in select centers. 1

Critical Pitfalls to Avoid

• Never perform major hepatic resection in patients with Child-Pugh B or C cirrhosis – mortality is unacceptably high 3
• Do not offer resection to patients with clinically significant portal hypertension (HVPG >10 mmHg) – risk of hepatic decompensation is prohibitive 1, 3
• Avoid systemic therapy in patients with potentially curative disease – resection, transplant, or ablation provide superior outcomes 4
• Do not delay multidisciplinary evaluation – treatment windows may close rapidly with tumor progression 1