Hepatocellular Carcinoma: Concerning Findings and Treatment
Concerning Diagnostic Findings
The most concerning findings for HCC include a hypervascular liver mass >2 cm on imaging (ultrasound, MRI, or CT) combined with AFP >400 ng/ml in a patient with cirrhosis, which is diagnostic without requiring biopsy. 1
Key Clinical Red Flags
- Vascular invasion (T2 or T3 disease) indicates aggressive tumor biology and significantly worsens prognosis, requiring systemic therapy rather than locoregional treatment 1, 2
- Multiple tumors >5 cm or tumor involving major portal/hepatic vein branches (T3) represents intermediate to advanced disease 1
- Direct invasion of adjacent organs (T4) or nodal involvement (N1) or distant metastasis (M1) indicates advanced disease with no curative options 1
- Child-Pugh grade C cirrhosis is a critical finding that precludes all curative treatments and limits patients to supportive care only 1, 3
- Clinically significant portal hypertension (esophageal varices, ascites, portal hypertensive gastropathy) is an absolute contraindication to surgical resection 3
Essential Staging Workup
- Chest X-ray or CT and abdominal CT/MRI to detect extrahepatic spread 1, 2
- AFP measurement (>400 ng/ml is diagnostic in cirrhotic patients with appropriate imaging findings) 1
- Child-Pugh classification and MELD score to assess hepatic functional reserve 1, 2
- Assessment for portal hypertension severity 3
Critical pitfall: Do not perform preoperative biopsy in potentially resectable tumors with AFP >400 ng/ml, as this delays surgery and risks tumor seeding along the biopsy tract 1
Treatment Algorithm by Stage
Very Early and Early Stage (BCLC 0-A: Single tumor, no vascular invasion, Child-Pugh A-B)
Surgical resection is the definitive first-line treatment for patients without cirrhosis or with compensated cirrhosis (Child-Pugh A, no portal hypertension, adequate future liver remnant ≥20-40%). 1, 3, 4
- For non-cirrhotic liver: Proceed directly to surgical resection regardless of tumor size if R0 resection achievable, with 5-year survival of 50-68% 3, 4
- For cirrhotic liver with Child-Pugh A: Resection is safe (perioperative mortality <5%) if no clinically significant portal hypertension and adequate remnant volume 3, 4
- For tumors ≤2-3 cm: Radiofrequency ablation (RFA) or microwave ablation (MWA) is equally effective as resection and should be considered first-line, particularly if portal hypertension present 1, 4
- For decompensated cirrhosis within Milan criteria (single tumor <5 cm or ≤3 nodules ≤3 cm): Liver transplantation is first-line treatment, with living donor transplantation achieving 85% 1-year and 70% 5-year survival 3, 4
Critical pitfall: Never offer resection to Child-Pugh C patients—mortality risk is prohibitive 3
Intermediate Stage (BCLC B: Multifocal HCC, no vascular invasion, Child-Pugh A-B)
Transarterial chemoembolization (TACE) is the standard of care for multifocal HCC with preserved liver function and no vascular invasion or extrahepatic spread. 1, 2
- TACE is appropriate only for patients with adequate hepatic functional reserve (Child-Pugh A or favorable B) 1
- Alternative locoregional options include percutaneous ethanol injection for <4 nodules ≤5 cm or RFA for tumors <5 cm and ≤4 in number 1
- For patients listed for transplant, neoadjuvant locoregional therapy reduces waiting list dropout from disease progression 2, 3
Advanced Stage (BCLC C: Vascular invasion and/or extrahepatic spread)
For unresectable HCC, lenvatinib is FDA-approved first-line systemic therapy, dosed at 12 mg daily for patients ≥60 kg or 8 mg daily for patients <60 kg. 5
- Atezolizumab plus bevacizumab is the preferred first-line immune checkpoint inhibitor-based regimen for advanced HCC 2
- Sorafenib extended survival by 2.8 months in phase III trials and remains an alternative first-line option 1
- Systemic chemotherapy (anthracyclines, cisplatin, 5-FU) has only 10% response rate with no survival benefit and should be reserved for clinical trials 1
Critical pitfall: Do not proceed with transplantation in patients with macrovascular invasion or extrahepatic disease—outcomes are universally poor 3
End-Stage (BCLC D: Child-Pugh C or poor performance status)
Best supportive care only—no active cancer treatment should be offered to Child-Pugh C patients with HCC exceeding transplant criteria. 1, 2
Special Treatment Considerations
Adjuvant Therapy After Resection
- Atezolizumab plus bevacizumab improves recurrence-free survival after resection, though longer-term data are still needed 2, 3
- Antiviral therapy for HBV or HCV reduces postoperative decompensation risk and prevents late recurrence 2
Surgical Approach
- Laparoscopic resection should be recommended when tumor location and surgeon expertise permit, offering reduced morbidity with equivalent oncological outcomes 3
Follow-Up Protocol
- After curative resection: AFP and liver imaging every 3-6 months for 2 years, as curative therapy can still be offered at relapse 1, 4
- Response assessment using modified RECIST criteria on dynamic CT or MRI 4
Key Prognostic Factors
- BCLC stage: 5-year survival 50-75% for early stage vs. <10% for advanced stage 2
- Tumor burden and vascular invasion: Most critical determinants of outcome 2
- Liver function (Child-Pugh class): Determines treatment eligibility and survival 1, 2
- Performance status: Essential for systemic therapy candidacy 2