What is the role of systemic chemotherapy in the management of a ruptured hepatocellular carcinoma (HCC)?

Management of Ruptured Hepatocellular Carcinoma: Role of Systemic Chemotherapy

Systemic chemotherapy is not recommended for the management of ruptured hepatocellular carcinoma (HCC) as it shows low objective response rates (<10%) without proven survival benefit and is poorly tolerated in these patients. 1

Initial Management of Ruptured HCC

• Transarterial embolization (TAE) is the treatment of choice for initial management of ruptured HCC, especially in hemodynamically unstable patients 2, 3
• TAE effectively arrests tumor bleeding with successful hemostasis reported in all patients in some series, allowing for subsequent definitive management 4
• After stabilization with TAE, careful evaluation including assessment of functional liver reserve, coagulopathy, tumor size and location should be performed before considering tumor resection 2

Treatment Algorithm After Initial Stabilization

For Patients with Preserved Liver Function (Child-Pugh A):

• First option: Staged hepatectomy after TAE for definitive treatment in suitable candidates 3, 5
• Second option: Sorafenib for patients with advanced HCC (BCLC stage C) who are not candidates for surgery but have well-preserved liver function 1, 6
  • Sorafenib has demonstrated survival benefit in advanced HCC (HR: 0.69, p=0.00058) with median survival of 10.7 months vs 7.9 months for placebo 6

For Patients with Intermediate Liver Function (Child-Pugh B):

• Transarterial chemoembolization (TACE) may be considered for patients with multinodular asymptomatic tumors without macroscopic vascular invasion or extrahepatic spread 1
• TACE with doxorubicin-eluting beads is recommended to minimize systemic side effects of chemotherapy 1

For Patients with Poor Liver Function (Child-Pugh C):

• Only symptomatic treatment is advocated as these patients have poor prognosis 1

Evidence Against Systemic Chemotherapy

• Traditional systemic chemotherapy containing anthracyclines, cisplatin, and 5-FU shows limited efficacy with only about 10% response rate and no proven survival benefit 1
• EASL-EORTC clinical practice guidelines explicitly state: "Systemic chemotherapy, tamoxifen, immunotherapy, anti-androgen, and herbal drugs are not recommended for the clinical management of HCC patients" 1
• Chemotherapy is poorly tolerated due to underlying cirrhosis, coexisting cytopenias and unpredictable pharmacokinetics 1

Current Systemic Therapy Options for Advanced HCC

• Sorafenib is the standard systemic therapy for patients with advanced HCC and well-preserved liver function (BCLC stage C) 1, 7
• Atezolizumab plus bevacizumab is now preferred as first-line treatment for advanced HCC with preserved liver function 7
• For second-line therapy after sorafenib failure, options include regorafenib, cabozantinib, or ramucirumab (if AFP ≥400 ng/mL) 7

Monitoring and Follow-up

• Response assessment should be based on dynamic CT or MRI studies using modified RECIST criteria 1
• Patients should be evaluated clinically for signs of liver decompensation and by imaging for tumor progression every 2 months to guide therapy decisions 1

Important Caveats

• Survival outcomes vary significantly based on liver function, with median survival after TAE for ruptured HCC reported as 126 days in one study 4
• Patients with elevated bilirubin levels (>50 μmol/L) have particularly poor outcomes 4
• The combination of TACE with sorafenib cannot be recommended outside clinical trials 1
• In case of progression or intolerance to sorafenib, best supportive care is preferred or patients should be included in clinical trials 1