What are the treatment options for a patient diagnosed with liver cancer?

Treatment Options for Liver Cancer (Hepatocellular Carcinoma)

Treatment selection for hepatocellular carcinoma depends on tumor stage using the Barcelona Clinic Liver Cancer (BCLC) staging system, liver function (Child-Pugh class), and performance status, with curative options (resection, transplantation, ablation) reserved for early-stage disease and systemic therapies for advanced disease. 1

Staging-Based Treatment Algorithm

Very Early and Early Stage (BCLC 0 and A)

For patients with preserved liver function (Child-Pugh A) and good performance status:

• Single tumors <2 cm: Both thermal ablation and surgical resection are equally recommended first-line options 2
• Single tumors >2 cm or 2-3 nodules ≤3 cm (Milan criteria): Three curative options exist 1:
  • Surgical resection if Child-Pugh class A, no clinically significant portal hypertension (HVPG ≤10 mmHg), and adequate future liver remnant volume 2
  • Liver transplantation is the preferred option for patients with decompensated cirrhosis or multifocal disease within Milan criteria 2, 3
  • Radiofrequency ablation (RFA) for patients who are not surgical candidates 1

Expected survival with curative treatment: 5+ years 1

Intermediate Stage (BCLC B)

For patients with large/multifocal tumors without vascular invasion or extrahepatic spread:

• Transarterial chemoembolization (TACE) is the first-line treatment, improving median survival from 16 to 22 months 1, 3
• Alternative locoregional therapies include transarterial embolization (TAE), radioembolization (SIRT), and stereotactic radiotherapy 1

Expected survival: >2.5 years 1

Advanced Stage (BCLC C)

For patients with vascular invasion, extrahepatic spread, or cancer-related symptoms with preserved liver function:

First-line systemic therapy options:

• Atezolizumab plus bevacizumab has become the preferred first-line treatment, showing superior overall survival and progression-free survival compared to sorafenib 4
• Lenvatinib is FDA-approved for first-line treatment of unresectable HCC, with weight-based dosing: 12 mg daily for patients ≥60 kg or 8 mg daily for patients <60 kg 5
• Sorafenib (multikinase inhibitor) improves median overall survival by approximately 3 months and remains an option 1, 6, 4

Second-line systemic therapy options:

• Nivolumab and pembrolizumab (immune checkpoint inhibitors) for patients who progress on first-line therapy 4
• Cabozantinib and regorafenib (tyrosine kinase inhibitors) 4

Expected survival: 50% at 1 year 1

Terminal Stage (BCLC D)

For patients with severe liver dysfunction (Child-Pugh C) or poor performance status (ECOG PS ≥2):

• Best supportive care and palliative medicine are recommended, as cancer-specific treatments will not improve survival and may worsen quality of life 1

Expected survival: <3 months 1

Absolute Contraindications to Surgical Resection

Do not perform hepatic resection in patients with: 2

• Child-Pugh class C cirrhosis
• Child-Pugh class B with major resection planned
• Clinically significant portal hypertension (HVPG >10 mmHg) with major resection planned

Critical Management Principles

Multidisciplinary Team Evaluation

Every patient must be evaluated by a multidisciplinary team including hepatologists, medical oncologists, interventional radiologists, radiation oncologists, and surgeons before treatment decisions are made 1

Adjuvant and Neoadjuvant Therapy

• Adjuvant atezolizumab plus bevacizumab improves recurrence-free survival after resection 2
• Neoadjuvant therapy is not recommended outside prospective studies 2

Surveillance for High-Risk Patients

Six-monthly surveillance with abdominal ultrasound plus serum alpha-fetoprotein should be performed in patients with cirrhosis from hepatitis B, hepatitis C, genetic hemochromatosis, or alcohol-related liver disease 3

Common Pitfalls to Avoid

• Do not biopsy potentially operable lesions due to risk of tumor seeding along the needle tract 3
• Do not delay antiviral therapy in patients with hepatitis B or C, as effective treatment reduces HCC risk and improves outcomes 3
• Do not perform major hepatic resection without assessing portal hypertension status, as HVPG >10 mmHg significantly increases perioperative mortality 2
• Do not overlook liver transplantation in patients with poor synthetic function but tumor burden within Milan criteria, as this may be their only curative option 3
• Expected perioperative mortality should be 2-3% in cirrhotic patients; if higher, reconsider the treatment approach 2

Geographic Considerations

In Asian countries, hepatitis B is the predominant cause of HCC (except Japan, Saudi Arabia, Egypt, and Pakistan where hepatitis C predominates), and treatment guidelines may expand indications beyond strict BCLC criteria with combination and alternative therapies 1