Treatment Options for Hepatocellular Carcinoma
For patients with hepatocellular carcinoma, treatment selection depends on tumor stage, liver function (Child-Pugh class), and presence of portal hypertension, with surgical resection being first-line for solitary tumors with preserved liver function, liver transplantation for decompensated cirrhosis meeting Milan criteria, and atezolizumab plus bevacizumab for advanced disease. 1, 2
Treatment Algorithm by Clinical Scenario
Early Stage HCC (BCLC 0-A) with Preserved Liver Function
Surgical resection is the definitive first-line treatment for patients with solitary tumors, Child-Pugh A cirrhosis, no clinically significant portal hypertension (hepatic venous pressure gradient ≤10 mmHg or platelet count ≥100,000), and adequate future liver remnant (≥20-40% of total liver volume). 3, 1, 2 This achieves 5-year survival rates of 50-68% with perioperative mortality of 2-3% in cirrhotic patients. 2
For non-cirrhotic patients (5% of Western cases, 40% in Asia), surgical resection is the clear first choice, as major resections can be performed with low complication rates and 5-year survival of 30-50%. 3
Anatomical resections are recommended over non-anatomical approaches, though this recommendation is based on retrospective data and should be balanced against preserving adequate hepatic function. 3
Early Stage HCC with Decompensated Cirrhosis
Liver transplantation is first-line treatment for patients meeting Milan criteria (single tumor <5 cm or ≤3 nodules ≤3 cm each) who have impaired liver function or decompensated cirrhosis. 3, 2 This achieves 1-, 3-, and 5-year survival rates of 85%, 75%, and 70%, respectively, with perioperative mortality of approximately 3%. 2
Transplantation is superior to other treatments because it removes both the tumor and the underlying diseased liver. 3
Child-Pugh C patients should receive only supportive care, not transplantation or resection. 3
Very Early HCC (BCLC 0) or Resection-Ineligible Patients
Radiofrequency ablation (RFA) or microwave ablation (MWA) is recommended for tumors ≤3 cm, particularly single nodules <2 cm, or patients unsuitable for resection due to comorbidities or borderline liver function. 3, 2
RFA provides superior local control compared to percutaneous ethanol injection (PEI), especially for tumors >2 cm. 2
For tumors <2 cm, either RFA or PEI can be used, though RFA is generally preferred. 3
Intermediate Stage HCC (BCLC B)
Transarterial chemoembolization (TACE) is the standard of care for multifocal HCC with preserved liver function (Child-Pugh A or favorable B), no vascular invasion, and no extrahepatic spread. 3, 1 Two randomized controlled trials have established TACE as superior to no treatment for unresectable HCC. 3
TACE is contraindicated when bilirubin >2 mg/dL unless segmental injections can be performed. 4
Portal vein thrombosis or large esophageal varices are contraindications to TACE. 3
Advanced Stage HCC (BCLC C)
Atezolizumab plus bevacizumab is the preferred first-line systemic therapy for advanced HCC with preserved liver function (Child-Pugh A) and adequate performance status. 1 This immune checkpoint inhibitor-based regimen has become the standard of care for advanced disease.
Sorafenib remains an alternative first-line option, having extended survival by 2.8 months in phase III trials (median OS 10.7 vs 7.9 months). 3, 1, 5 The recommended dose is 400 mg orally twice daily without food. 5
Regorafenib is indicated for second-line treatment in patients who progressed on sorafenib, provided they tolerated sorafenib at ≥400 mg daily for a median of 7.8 months. 6 In the RESORCE trial, regorafenib improved median OS to 10.6 months versus 7.8 months with placebo (HR 0.63, p<0.0001). 6
Lenvatinib is another first-line alternative when immunotherapy is contraindicated or unavailable. 4
Critical Patient Selection Criteria
Liver Function Assessment
Child-Pugh classification determines treatment eligibility:
Child-Pugh A: Eligible for all treatments including resection, transplantation, ablation, TACE, and systemic therapy. 3
Child-Pugh B (favorable): Consider transplantation, TACE, or systemic therapy; avoid resection. 3
Child-Pugh C: Supportive care only. 3
Portal Hypertension Assessment
Clinically significant portal hypertension is defined as hepatic venous pressure gradient >10 mmHg or platelet count <100,000, and represents a contraindication to resection due to increased perioperative mortality. 3
Performance Status
ECOG performance status 0-1 is required for systemic therapy candidacy. 1 Patients with ECOG ≥2 should receive best supportive care.
Post-Treatment Surveillance
After curative resection or ablation, perform AFP measurement and dynamic liver imaging (CT or MRI) every 3-6 months for at least 2 years, as curative therapy can still be offered at relapse. 3, 1, 2 Recurrence occurs in 50-70% of patients after resection. 2
Response assessment should use modified RECIST criteria on dynamic CT or MRI. 1
Monitor for hepatic decompensation, particularly in patients with underlying cirrhosis. 3
Critical Pitfalls to Avoid
Never perform TACE when bilirubin >2 mg/dL unless segmental injection is possible, as this significantly increases hepatotoxicity and mortality risk. 4
Do not offer resection to Child-Pugh C patients due to prohibitive risk of postoperative liver failure. 2
Avoid systemic chemotherapy with traditional cytotoxic agents (anthracyclines, cisplatin, 5-FU), as these achieve only 10% response rates with no survival benefit and unacceptable toxicity in cirrhotic patients. 3
The STORM trial definitively showed that adjuvant sorafenib after resection or ablation does not prevent recurrence (33.4 vs 33.8 months) or reduce mortality, with 30% of patients discontinuing due to adverse effects within 3 months. 3
Overall survival, not disease-free survival, is the preferred endpoint for comparing treatments, as DFS can be misleading in HCC patients who face competing risks of death from cirrhosis versus tumor progression. 3
Multidisciplinary Team Approach
All HCC patients should be evaluated by a multidisciplinary team including hepatologists, surgeons, interventional radiologists, medical oncologists, pathologists, and diagnostic radiologists. 3, 7, 8, 9 This approach is essential given the complexity of balancing tumor stage, liver function, and treatment options.