What is the initial workup and treatment for hepatocellular carcinoma (HCC)?

Workup and Treatment of Hepatocellular Carcinoma

The initial workup of hepatocellular carcinoma requires comprehensive staging with dynamic CT or MRI, liver function assessment, and performance status evaluation, followed by treatment based on the Barcelona Clinic Liver Cancer (BCLC) staging system, which stratifies patients into treatment pathways including surgical resection, liver transplantation, ablation, transarterial therapies, or systemic therapy. 1

Initial Diagnostic Workup

Clinical Assessment

• History and examination
  • Risk factors: HBV/HCV infection, alcohol intake, IV drug use
  • Signs of chronic liver disease: jaundice, ascites, encephalopathy, splenomegaly
  • Performance status and nutritional state evaluation

Laboratory Evaluation

• Liver function assessment
  • Prothrombin time, albumin, bilirubin (Child-Pugh classification)
  • Platelets (for portal hypertension assessment)
• Etiology workup
  • HBV/HCV serology, iron studies, autoimmune markers
• Tumor markers
  • Alpha-fetoprotein (AFP) - levels >400 ng/ml can be diagnostic in cirrhotic patients with hypervascular lesions >2cm 1

Imaging Studies

• Dynamic (multiphasic) CT or MRI for diagnosis and staging:
  • Number and size of nodules
  • Vascular invasion assessment
  • Extrahepatic spread evaluation 2
• Additional imaging for advanced disease:
  • Chest CT
  • Bone scan (if clinically indicated) 2

Portal Hypertension Assessment

• Upper endoscopy to evaluate for varices/hypertensive gastropathy
• Optional: transjugular measurement of hepatic-venous pressure gradient 2

Pathological Diagnosis

• Biopsy may be required when imaging is inconclusive
• Stromal invasion is the defining histological feature of HCC 2

Treatment Algorithm Based on BCLC Staging

Very Early Stage (BCLC 0)

• Single tumor <2 cm, Child-Pugh A, no portal hypertension
• First-line treatment: Radiofrequency ablation (RFA) or surgical resection 1
• 5-year survival rates: 50-75% with surgical resection 1

Early Stage (BCLC A)

• Single tumor or up to 3 nodules ≤3 cm, Child-Pugh A-B
• Treatment options:
  1. Surgical resection - for single lesions with preserved liver function and no significant portal hypertension
  2. Liver transplantation - for tumors within Milan criteria (single lesion <5 cm or up to 3 nodules ≤3 cm) in patients with decompensated cirrhosis
  3. Thermal ablation - for patients not suitable for surgery 1

Intermediate Stage (BCLC B)

• Multinodular tumors, Child-Pugh A-B, no vascular invasion
• Standard treatment: Transarterial chemoembolization (TACE)
• Best candidates: solitary tumors <7 cm or <4 tumors, Child-Pugh A or B7 without ascites 1
• Options include conventional TACE, TACE with drug-eluting beads, or transarterial embolization (TAE) 1

Advanced Stage (BCLC C)

• Vascular invasion, extrahepatic spread, or cancer-related symptoms
• First-line systemic therapy:
  • Atezolizumab plus bevacizumab (preferred)
  • Alternatives: Lenvatinib or sorafenib 1, 3
• Lenvatinib is FDA-approved for first-line treatment of unresectable HCC 3

End-Stage (BCLC D)

• Severe liver dysfunction, poor performance status
• Approach: Best supportive care 1

Special Considerations

Follow-up and Response Assessment

• Dynamic CT or MRI every 3 months for first 2 years after curative treatments
• Every 6 months thereafter
• Response assessment using modified RECIST criteria 1

Common Pitfalls to Avoid

1. Delaying diagnosis - Regular surveillance with ultrasound every 6 months is recommended for high-risk patients (cirrhosis, chronic HBV) 2
2. Inappropriate treatment selection - Treatment must consider tumor characteristics, liver function, and performance status 1
3. Overlooking multidisciplinary approach - Management requires coordination between hepatologists, radiologists, surgeons, and oncologists 1
4. Inadequate staging - Comprehensive staging is essential before initiating treatment 1
5. Neglecting liver function monitoring - Regular assessment during treatment is crucial to prevent hepatotoxicity 1

By following this structured approach to diagnosis and treatment based on BCLC staging, clinicians can optimize outcomes for patients with hepatocellular carcinoma, focusing on reducing mortality and improving quality of life.