What is the initial approach to treating hepatocellular carcinoma (HCC)?

Initial Approach to Treating Hepatocellular Carcinoma

All HCC patients must be evaluated by a multidisciplinary team including hepatologists, surgeons, interventional radiologists, and oncologists to determine the optimal treatment strategy based on tumor stage, liver function (Child-Pugh class), and performance status. 1, 2

Immediate Assessment Requirements

Before any treatment decision, obtain:

• Staging imaging: Triphasic CT or dynamic contrast-enhanced MRI of the abdomen to assess tumor burden, vascular invasion, and extrahepatic spread 1, 2, 3
• Liver function assessment: Child-Pugh classification and MELD score (mandatory for transplant candidates) 1, 4
• Performance status: ECOG score to determine systemic therapy candidacy 2, 4
• Chest CT: Required for transplant candidates and to detect metastases 1
• AFP level: Hypervascular mass >2 cm with AFP >400 ng/mL in cirrhotic patients is diagnostic without biopsy 2

Treatment Algorithm by Disease Stage

Very Early/Early Stage (BCLC 0-A)

First-line curative options in order of preference:

1. Surgical resection - For patients with:

   • Single tumor, any size (typically <5 cm practical limit) 1
   • Child-Pugh A cirrhosis with normal bilirubin 1, 4
   • No clinically significant portal hypertension (hepatic venous pressure gradient ≤10 mmHg or platelets ≥100,000) 4
   • Non-cirrhotic liver (best outcomes: 54% 3-year survival) 1
   • Expected perioperative mortality: 2-3% 4

2. Liver transplantation - For patients with:

   • Milan criteria: single tumor ≤5 cm OR ≤3 nodules each ≤3 cm, no vascular invasion 1, 4
   • Expanded UCSF criteria: single tumor ≤6.5 cm OR 2-3 tumors none >4.5 cm with total diameter ≤8 cm 1
   • Child-Pugh A or B cirrhosis precluding resection 1
   • 3-year survival up to 88% 1
   • Critical: If waiting time >6 months, perform bridging therapy with ablation or resection 1

3. Percutaneous ablation (RFA/MWA) - For patients with:

   • Tumors ≤3 cm 2, 4
   • Not surgical candidates due to comorbidities or liver dysfunction 1
   • Child-Pugh A-B 1

Intermediate Stage (BCLC B)

Transarterial chemoembolization (TACE) is the standard of care for:

• Multinodular tumors without vascular invasion 1, 2, 4
• No extrahepatic spread 1, 4
• Child-Pugh A (preferred) or selected B patients 1
• Preserved portal flow 1
• Improves 2-year survival by 20-60% 4

Contraindications to TACE:

• ECOG performance status ≥2 1
• Severe hepatic decompensation 1
• Portal vein thrombosis 1

Advanced Stage (BCLC C)

First-line systemic therapy options:

1. Atezolizumab plus bevacizumab (preferred regimen):

   • Superior survival outcomes compared to sorafenib 2, 4
   • Mandatory: Perform endoscopy before starting bevacizumab to assess for varices and bleeding risk 1
   • Treat small varices with nonselective beta-blockers immediately 1
   • Band ligation for larger varices 1

2. Lenvatinib (alternative first-line):

   • FDA-approved for first-line unresectable HCC 5
   • Dosing: 12 mg daily if ≥60 kg OR 8 mg daily if <60 kg 5
   • Requires Child-Pugh A liver function 5

3. Sorafenib (alternative first-line):

   • Extended survival by 2.8 months in phase III trials 2
   • Option when immunotherapy contraindicated or unavailable 1, 2

Terminal Stage (BCLC D)

Best supportive care only for:

• Child-Pugh C patients with tumors exceeding transplant criteria 1
• ECOG performance status ≥3 4

Critical Treatment Selection Factors

Liver function determines treatment eligibility:

• Child-Pugh A: All treatment options available 1, 4
• Child-Pugh B: Selected patients for transplantation, TACE, or carefully chosen systemic therapy 1, 4
• Child-Pugh C: Transplantation only if within Milan criteria; otherwise supportive care only 1, 4

Vascular invasion mandates systemic therapy rather than locoregional treatment, as it indicates aggressive biology and significantly worsens prognosis 2

Post-Treatment Surveillance

After curative therapy (resection/ablation/transplantation):

• AFP and liver imaging every 3-6 months for 2 years 2
• Use modified RECIST criteria on dynamic CT/MRI for response assessment 2, 4
• Recurrence is common; re-evaluate for repeat curative therapy if localized 1

Common Pitfalls to Avoid

• Never delay multidisciplinary evaluation - Treatment decisions require input from multiple specialties given the complexity of balancing tumor burden and liver dysfunction 1
• Do not perform biopsy on potentially resectable lesions - Risk of tumor seeding along biopsy tract 1
• Do not start bevacizumab without endoscopy - Variceal bleeding risk is more immediately life-threatening than HCC progression 1
• Do not offer TACE to patients with portal vein thrombosis - Contraindicated due to risk of hepatic decompensation 1
• Do not use systemic therapy in Child-Pugh C patients outside transplant candidates - Unacceptable toxicity without survival benefit 1, 4