Hepatocellular Carcinoma Treatment Guidelines
Treatment Selection Based on BCLC Staging System
The Barcelona Clinic Liver Cancer (BCLC) staging system should guide all treatment decisions for HCC patients with underlying cirrhosis, as it integrates tumor extent, liver function, portal pressure, and performance status to determine optimal therapy. 1
Very Early and Early Stage HCC (BCLC 0 and A)
Surgical Resection
- Surgical resection is the first-line treatment for solitary HCC of any size in patients with preserved liver function (Child-Pugh A), no clinically significant portal hypertension, and adequate future liver remnant volume (≥40% for cirrhotic liver). 1, 2
- In non-cirrhotic liver, resection is the primary option for localized resectable tumors, achieving 3-year survival of 54% with R0 resections 1
- Resection provides 5-year survival rates of 50-80% in well-selected candidates 3
Liver Transplantation
- Liver transplantation should be considered for patients meeting Milan criteria (single tumor ≤5 cm or up to 3 tumors each ≤3 cm, no vascular invasion) who are not suitable for resection, offering 3-year survival up to 88%. 1
- Expanded UCSF criteria (single tumor ≤6.5 cm; 2-3 tumors none >4.5 cm; total tumor diameter ≤8 cm) may also be considered 1
- MELD score is mandatory for transplant evaluation 1
Thermal Ablation
- Radiofrequency ablation (RFA) or microwave ablation is first-line treatment for solitary tumors <2 cm (BCLC 0) and an alternative to resection for single nodules 2-3 cm when surgery is not feasible due to tumor location, portal hypertension, or comorbidities. 1
- RFA provides better local control than percutaneous ethanol injection (PEI), especially for tumors >2 cm 1
- Thermal ablation can treat up to 3 tumors each <3 cm 1
- Adjuvant atezolizumab plus bevacizumab may improve recurrence-free survival after ablation, though longer follow-up is required before routine recommendation 1
Intermediate Stage HCC (BCLC B)
Transarterial Therapy
- Transarterial chemoembolization (TACE) or transarterial embolization (TAE) is the standard of care for intermediate-stage HCC in patients with preserved liver function (Child-Pugh A or B7 without ascites), performance status ECOG <2, and limited tumor burden (solitary nodule <7 cm or fewer than 4 tumors). 1
- TACE with drug-eluting beads is recommended to minimize systemic chemotherapy side effects 1
- TACE improves survival from 16 to 22 months in appropriate candidates 1
- TACE is contraindicated in patients with decompensated liver disease, advanced kidney dysfunction, macroscopic vascular invasion, or extrahepatic spread. 1
- TACE should not be combined with multikinase inhibitors outside clinical trials 1
Selective Internal Radiation Therapy (SIRT)
- SIRT may be considered for large solitary tumors or tumors with local macrovascular invasion when systemic therapy tolerance is a concern, though the optimal patient subgroup remains undefined 1
Advanced Stage HCC (BCLC C)
First-Line Systemic Therapy
- Atezolizumab plus bevacizumab is now the first-choice standard of care for advanced HCC with preserved liver function, based on superior efficacy. 1
- Patients require careful assessment for contraindications to either drug, with upper GI endoscopy within 6 months to evaluate and treat varices in those with portal hypertension 1
- For patients with contraindications to intravenous therapy or who decline it, sorafenib and lenvatinib are alternative first-line oral therapies. 1
- Lenvatinib dosing for HCC: 12 mg daily for patients ≥60 kg or 8 mg daily for patients <60 kg, taken orally until disease progression or unacceptable toxicity 4
Second-Line Options
- Nivolumab plus ipilimumab is approved for HCC patients previously treated with sorafenib, though this indication is under accelerated approval 5
Terminal Stage HCC (BCLC D)
- Child-Pugh C patients should receive only supportive care if their tumor exceeds transplant listing criteria. 1
- Best supportive care is the only recommendation for patients with decompensated liver disease and poor performance status 1
Critical Contraindications and Pitfalls
What NOT to Do
- Traditional systemic chemotherapy (anthracyclines, cisplatin, 5-FU) is NOT recommended for HCC management, showing only 10% response rate with no proven survival benefit and poor tolerance due to underlying cirrhosis. 1, 6
- Neo-adjuvant or adjuvant therapies after resection or ablation are not recommended, as they have not proven to improve outcomes 1
- Radiotherapy is not standard treatment for resectable HCC 2
Essential Pre-Treatment Assessment
- Evaluate liver function using Child-Pugh classification and portal hypertension severity 1
- Calculate future liver remnant volume: minimum ≥20% for normal liver, ≥30% for chronic liver disease, ≥40% for cirrhotic liver 3
- Consider portal vein embolization if future liver remnant is inadequate 3
- Confirm absence of macroscopic vascular invasion and extrahepatic metastases before resection 2
Surveillance and Follow-Up
- Surveillance with dynamic CT or MRI every 3-6 months for at least 2 years is essential post-treatment, as recurrence rates reach 50-60% at 5 years. 2, 3
- Response assessment should use modified RECIST criteria on dynamic imaging 3
- For patients at risk, abdominal ultrasound surveillance every 6 months is recommended 1
Multidisciplinary Approach
- Every HCC patient's treatment plan must be discussed and planned by a multidisciplinary team, considering tumor extent, liver function, growth pattern, hepatic functional reserve, and performance status. 1