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

Workup and Treatment for Hepatocellular Carcinoma

The initial workup for hepatocellular carcinoma (HCC) should include dynamic CT or MRI for diagnosis and staging, followed by treatment based on the Barcelona Clinic Liver Cancer (BCLC) staging system, with surgical resection, liver transplantation, or ablation for early stages, locoregional therapies for intermediate stages, and systemic therapy with atezolizumab plus bevacizumab or lenvatinib for advanced disease. 1

Diagnostic Workup

Clinical Assessment

• Evaluate risk factors: IV drug use, alcohol intake, metabolic syndrome (obesity, diabetes, hypertension) 2
• Assess symptoms and signs of chronic liver disease: jaundice, ascites, encephalopathy, bleeding, splenomegaly 2
• Determine performance status to distinguish cancer-related symptoms from cirrhosis-related symptoms 2

Laboratory Tests

• Etiology of liver disease: HBV (HBsAg, anti-HBc), HCV (anti-HCV), iron status, autoimmune markers 2
• Liver function: prothrombin time, albumin, bilirubin 2
• Complete blood count including platelets 2
• Tumor marker: serum alpha-fetoprotein (AFP) 2
  • AFP >400 ng/ml can be diagnostic in patients with cirrhosis and a focal hypervascular liver lesion >2 cm 1

Imaging Studies

• Liver dynamic (multiple phase) MRI or CT for diagnosis and evaluation of tumor extent 2, 1
  • Number and size of nodules
  • Vascular invasion
  • Extrahepatic spread
• Chest CT to rule out extrahepatic spread 2
• Consider bone scan in advanced disease 2, 1

Portal Hypertension Assessment

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

Tumor Biopsy

• Indicated for nodules with non-diagnostic imaging findings 2
• Required to diagnose HCC in non-cirrhotic liver 2
• Stromal invasion is the defining histological feature of HCC 2

Staging

The Barcelona Clinic Liver Cancer (BCLC) staging system is recommended for treatment allocation 2, 1:

Stage	Description	Recommended Treatment
Very early (BCLC 0)	Single tumor <2 cm, Child-Pugh A, no portal hypertension	Resection, ablation
Early (BCLC A)	Single or ≤3 nodules ≤3 cm, Child-Pugh A-B, PS 0	Resection, transplantation, ablation
Intermediate (BCLC B)	Multinodular, Child-Pugh A-B, PS 0	TACE
Advanced (BCLC C)	Portal invasion, nodal involvement, metastases, PS 1-2	Systemic therapy
Terminal (BCLC D)	Child-Pugh C, PS >2	Symptomatic treatment

Treatment Approaches

Early Stage HCC (BCLC 0-A)

1. Surgical Resection

   • First choice for single tumors in patients without advanced fibrosis 1
   • Effective and safe (mortality <5%) in early BCLC stages with single lesion, good performance status, and no clinically important portal hypertension 2
   • 5-year recurrence rate: 50-70% 2

2. Liver Transplantation

   • Recommended for patients with solitary lesion <5 cm or up to 3 nodules ≤3 cm (Milan criteria) not suitable for resection 1
   • Consider for Child-Pugh C patients with tumor extent within Milan criteria 2

3. Ablation Techniques

   • Radiofrequency ablation (RFA) is first-line treatment for solitary tumors <2 cm in compensated cirrhosis 1
   • Percutaneous ethanol injection (PEI) is an alternative, but RFA provides better local control 1

Intermediate Stage HCC (BCLC B)

Transarterial Chemoembolization (TACE)

• Standard of care for patients with limited tumor burden, preserved liver function, and good performance status 1

Advanced Stage HCC (BCLC C)

1. First-line Systemic Therapy

   • Atezolizumab plus bevacizumab is the current first-line treatment for advanced HCC 1
   • Lenvatinib is FDA-approved for first-line treatment of unresectable HCC 1, 3
     • Dosing based on weight: 12 mg for patients ≥60 kg or 8 mg for patients <60 kg 3
   • Sorafenib is an alternative first-line option for advanced HCC with well-preserved liver function 1

2. Second-line Therapy

   • Regorafenib for patients previously treated with sorafenib 4

Terminal Stage HCC (BCLC D)

• Symptomatic treatment and best supportive care 2

Follow-up and Monitoring

• Dynamic CT or MRI every 3 months for the first 2 years after curative treatments, and every 6 months thereafter 1
• Response assessment using modified RECIST criteria 1
• Regular monitoring of liver function during treatment 1

Common Pitfalls and Caveats

1. Surveillance Importance

   • Surveillance with ultrasound every 6 months is crucial for high-risk patients (cirrhosis, chronic HBV) 1
   • Adding AFP to US can lead to a 6% gain in early detection rate, but increases false positives 2

2. Treatment Selection Challenges

   • Up to one-third of patients may not fit standard guidelines due to advanced age, comorbidities, or tumor location 1
   • Multidisciplinary approach involving hepatologists, radiologists, surgeons, and oncologists is essential 1

3. Post-Treatment Recurrence

   • High recurrence rate (50-70% at 5 years) following surgery necessitates close monitoring 2
   • Microvascular invasion is a predictor of recurrence and survival 2

4. Risk Reduction

   • Patients with HCV infection and advanced fibrosis remain at increased risk for HCC even after achieving sustained virological response following antiviral treatment 2
   • Continued surveillance is necessary in these patients 2