What is the management for a patient with a large heterogeneous enhancing lesion (15x10 cm) in the right lobe of the liver, mild ascites, tumoral thrombosis of the right and main portal vein, and an alpha-fetoprotein (AFP) level of 35?

Management of Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

This patient with a large 15x10 cm HCC, main portal vein tumor thrombosis, and mild ascites should receive systemic therapy with atezolizumab plus bevacizumab as first-line treatment, provided they meet eligibility criteria (no high-risk varices, Child-Pugh A cirrhosis, ECOG 0-1). 1, 2

Diagnosis Confirmation

The clinical presentation is diagnostic of HCC without requiring biopsy:

• Large heterogeneous enhancing lesion >2 cm with typical imaging features (arterial hyperenhancement with washout) in a cirrhotic liver establishes HCC diagnosis 1
• AFP of 35 ng/mL is mildly elevated but non-diagnostic (diagnostic threshold is >200-400 ng/mL), however imaging characteristics alone are sufficient for lesions >2 cm 1
• Biopsy is not indicated when diagnosis is clear on imaging and patient is proceeding to systemic therapy 1

Disease Staging and Prognosis

This represents Barcelona Clinic Liver Cancer (BCLC) Stage C (advanced stage) disease due to:

• Main portal vein tumor thrombosis (Vp4 classification) 3
• Large tumor size (15 cm) with likely macrovascular invasion 1
• Mild ascites suggesting compromised liver function 1

Portal vein tumor thrombosis involving the main trunk (Vp4) carries particularly poor prognosis with median survival of 5.3 months with sorafenib and 0.7 months with best supportive care 3. However, the relatively low AFP level (<400 ng/mL) is a favorable prognostic factor even in the presence of portal vein thrombosis 4.

First-Line Systemic Therapy

Atezolizumab 1200 mg IV plus bevacizumab 15 mg/kg IV every 3 weeks is the recommended first-line treatment 2:

• This combination demonstrated superior overall survival (median not reached vs 13.2 months) compared to sorafenib with hazard ratio 0.58 (95% CI 0.42-0.79, p=0.0006) 2
• Progression-free survival was 6.8 months vs 4.3 months (HR 0.59, p<0.0001) 2
• Objective response rate was 28% vs 12% with sorafenib 2

Critical Eligibility Requirements Before Starting Atezolizumab/Bevacizumab:

Must exclude or manage the following 2:

• Evaluate for esophageal varices within past 6 months - patients with untreated or incompletely treated varices with bleeding or high risk of bleeding are excluded 2
• Confirm Child-Pugh A cirrhosis - Child-Pugh B or C patients are excluded 2
• Assess ascites severity - moderate to severe ascites is an exclusion criterion 2
• ECOG performance status must be 0 or 1 2
• No history of hepatic encephalopathy 2
• No autoimmune disease or recent immunosuppressive medications 2

Alternative Treatment Considerations

When Atezolizumab/Bevacizumab is Contraindicated:

Sorafenib 400 mg orally twice daily remains an option 1, 2, though with inferior outcomes compared to atezolizumab/bevacizumab.

Role of Locoregional Therapy:

Surgical resection is NOT appropriate for this patient due to:

• Main portal vein thrombosis (Vp4) - resection shows benefit only in segmental PVTT (Vp1) with median survival 32.4 months 3
• Large tumor size (15 cm) exceeding resectability criteria 1
• Presence of ascites suggesting decompensated liver function 1

Transarterial chemoembolization (TACE) is relatively contraindicated due to main portal vein thrombosis, which increases risk of hepatic decompensation and has limited efficacy (median survival 3.6 months for Vp4) 3, 5.

Monitoring and Supportive Care

Tumor assessments should be performed every 6 weeks for the first 54 weeks, then every 9 weeks thereafter 2:

• Use contrast-enhanced CT or MRI per RECIST v1.1 criteria 2
• Monitor AFP levels serially - rising AFP indicates disease progression even with stable imaging 1

Manage portal hypertension complications 1:

• Endoscopic surveillance and prophylaxis for varices if present 1
• Diuretics for ascites management 1
• Monitor for hepatic encephalopathy 2

Critical Pitfalls to Avoid

• Do not delay systemic therapy to pursue locoregional treatments - main portal vein thrombosis is an indication for immediate systemic therapy, not TACE or resection 1, 3
• Do not start bevacizumab without variceal screening - untreated high-risk varices are an absolute contraindication due to bleeding risk 2
• Do not assume all patients with PVTT have the same prognosis - extent of PVTT (Vp1-4 classification) and AFP level significantly impact outcomes 3, 4
• Do not use AFP level alone to exclude HCC - 25-50% of HCCs have normal AFP, and imaging is diagnostic for lesions >2 cm 1

Prognosis Discussion

With atezolizumab/bevacizumab, median overall survival was not reached in the trial (vs 13.2 months with sorafenib), representing a significant improvement over historical outcomes 2. However, main portal vein thrombosis remains an adverse prognostic factor 3, 4. The relatively low AFP level (35 ng/mL) is favorable and associated with improved survival compared to patients with elevated AFP and PVTT 4.