What are the current treatment recommendations for liver cancer?

Current Treatment Recommendations for Liver Cancer (Hepatocellular Carcinoma)

Treatment for hepatocellular carcinoma (HCC) should follow the Barcelona Clinic Liver Cancer (BCLC) staging system, which incorporates tumor burden, liver function, and performance status to guide optimal therapy selection for improved survival outcomes. 1, 2

Diagnosis and Staging

• HCC diagnosis in cirrhotic patients can be made non-invasively using characteristic imaging findings; however, biopsy should be considered if radiological criteria are not fulfilled 1
• In non-cirrhotic patients, the diagnosis of HCC should be based on pathology 1
• The BCLC staging system is the most widely validated and recommended system for prognostication and treatment allocation 1, 2
• Pathological confirmation is strongly recommended if systemic therapy is being considered 1

Treatment Options by BCLC Stage

Very Early Stage (BCLC 0) and Early Stage (BCLC A)

• Surgical resection is the preferred treatment for:

  • HCC in non-cirrhotic liver 1
  • Solitary HCC in cirrhotic liver when liver function is maintained and adequate remnant liver volume can be preserved 1
  • Patients with preserved liver function, no significant portal hypertension, and good performance status 2, 3

• Liver transplantation is recommended for:

  • Patients with decompensated cirrhosis and HCC within accepted criteria 1
  • Multifocal HCC within accepted criteria 1
  • Patients who meet Milan criteria (single tumor ≤5 cm or up to three nodules ≤3 cm) 2, 3

• Thermal ablation (radiofrequency or microwave) is recommended for:

  • Selected patients with solitary <2 cm HCC in compensated cirrhosis 1
  • Patients with up to three HCC tumors <3 cm who are not suitable for surgery 1
  • As an alternative first-line treatment to surgery for solitary tumors 2-3 cm 1

Intermediate Stage (BCLC B)

• Intra-arterial treatments are the standard of care:
  • Transarterial chemoembolization (TACE) or transarterial embolization (TAE) for patients with preserved liver function (Child-Pugh A or B7 without ascites) 1, 2
  • Best candidates have limited tumor burden (solitary nodule <7 cm or fewer than four tumors) 1
  • TACE/TAE should not be used in patients with decompensated liver disease, advanced kidney dysfunction, macroscopic vascular invasion, or extrahepatic spread 1

Advanced Stage (BCLC C)

• Systemic therapy is the mainstay of treatment:
  • The combination of atezolizumab and bevacizumab is now considered first-choice standard of care 1
  • Patients require careful assessment for contraindications, particularly the risk of variceal bleeding 1
  • Sorafenib and lenvatinib are alternative first-line therapies for patients with contraindications to atezolizumab/bevacizumab 1
  • For HCC previously treated with sorafenib, nivolumab in combination with ipilimumab is indicated 4

Terminal Stage (BCLC D)

• Best supportive care is recommended 1, 2
• Focus on symptom management and quality of life 2

Special Considerations

• Adjuvant therapy with atezolizumab and bevacizumab after resection or ablation may improve recurrence-free survival, but longer-term follow-up is required 1
• Laparoscopic resection should be considered in suitable patients 1
• Patients listed for transplant should be considered for neoadjuvant locoregional therapy while on the waiting list if technically possible 1
• Stereotactic radiotherapy is an option to ablate tumors in patients not suitable for surgery or conventional ablative techniques 1

Treatment Selection Pitfalls

• Up to one-third of patients do not fit standard recommendations due to advanced age, significant comorbidities, or strategic tumor location 2
• Tumor recurrence is a major complication after resection, with rates as high as 50-60% at 5 years 3
• TACE should not be combined with multikinase inhibitors despite promising early signals 1
• Vascular invasion and extrahepatic metastases are absolute contraindications for liver transplantation 1

Follow-up Recommendations

• After curative treatment, patients should be followed with AFP determination and liver imaging every 3-6 months for at least 2 years 1
• Response assessment should be based on dynamic CT or MRI studies using modified RECIST criteria 3