What are the diagnostic markers and treatment options for liver cancer?

Diagnostic Markers and Treatment Options for Liver Cancer

Alpha-fetoprotein (AFP) is the primary serum tumor marker for hepatocellular carcinoma (HCC), but it should not be used as the sole determinant for treatment decisions and must be combined with imaging studies for proper diagnosis and monitoring. 1

Diagnostic Markers for Liver Cancer

Serum Tumor Markers

• Alpha-fetoprotein (AFP): Primary tumor marker for HCC

  • Levels >400 ng/ml can be diagnostic in patients with cirrhosis and a focal hypervascular liver lesion (>2 cm) 1
  • Should not be used alone for treatment decisions 1
  • Most useful when disease is not easily measurable 1

• Additional markers used in some regions:

  • Des-gamma-carboxy prothrombin (DCP/PIVKA-II) 1, 2
  • AFP-L3 (LCA-reactive α-fetoprotein isoform) 2
  • In Japan, simultaneous measurement of AFP, DCP, and AFP-L3 is common 1

Imaging Diagnosis

1. First-line imaging studies 1:

   • Dynamic contrast-enhanced CT
   • Dynamic contrast-enhanced MRI with extracellular contrast agents
   • MRI with hepatocyte-specific contrast agents (e.g., Gd-EOB-DTPA)

2. Diagnostic criteria for HCC 1:

   • Arterial phase hyperenhancement (APHE)
   • Washout appearance in portal venous, delayed, or hepatobiliary phases
   • These criteria should be applied only to lesions without marked T2 hyperintensity or targetoid appearances

3. Second-line imaging 1:

   • Contrast-enhanced ultrasound (CEUS)
   • Diagnostic criteria: APHE with mild and late (≥60 seconds) washout

4. Biopsy:

   • Rarely required for diagnosis 1
   • Risk of tumor seeding in needle tract (1-3%) 1
   • Should be avoided for potentially operable lesions 1

Staging Systems

• TNM staging system 1
• Barcelona Clinic Liver Cancer (BCLC) staging system 3
• Child-Pugh classification for liver function assessment 3

Treatment Options

1. Localized Resectable Tumors

• Surgical resection (partial hepatectomy):

  • First choice for patients without cirrhosis 1, 3
  • For cirrhotic patients with well-preserved liver function (Child-Pugh A), normal bilirubin, and no portal hypertension 3
  • 5-year survival rates: 50-75% 3

• Liver transplantation:

  • Optimal for patients meeting Milan criteria (single tumor ≤5 cm or up to 3 nodules ≤3 cm) 3
  • For patients with Child-Pugh B/C cirrhosis or portal hypertension 3
  • 5-year survival >75% 3

2. Localized Unresectable Tumors

• Local ablation techniques:

  • Radiofrequency ablation (RFA): For tumors <5 cm and/or fewer than four in number 1, 3
  • Percutaneous ethanol injection (PEI): For patients with fewer than 3-4 tumor nodules, maximum 5 cm in size 1
  • RFA provides better local control than PEI, especially for tumors >2 cm 3

• Transarterial chemoembolization (TACE):

  • Standard for asymptomatic patients with multinodular tumors, Child-Pugh A/B cirrhosis, no vascular invasion or extrahepatic spread 1, 3
  • Expected survival benefit: 16-22 months 3
  • Drug-eluting beads may reduce systemic side effects 3

• Radioembolization:

  • Uses micron-sized embolic particles loaded with radioisotope (usually yttrium-90) 4
  • Targets tumor cells with high-dose radiation while sparing healthy hepatocytes 4

3. Advanced Disease

• Systemic therapy:

  • Sorafenib: First-line treatment for advanced HCC 3, 5
    • Extends survival by approximately 2.8 months 1, 3
    • Response rate: 8%, disease control: 41% 1
  • Lenvatinib: Alternative first-line treatment for unresectable HCC 5
  • Regorafenib: For patients who have progressed on sorafenib 3

• Best supportive care:

  • For patients with heavily impaired liver function or poor performance status 1

Follow-up and Monitoring

• After radical treatments 1:

  • Clinical evaluation of liver decompensation
  • Early detection of recurrence by dynamic CT or MRI every 3 months for first 2 years
  • Surveillance every 6 months thereafter

• For advanced HCC treated with TACE or systemic agents 1:

  • Clinical evaluation for liver decompensation
  • Dynamic CT or MRI for tumor progression every 2 months

Common Pitfalls and Caveats

1. Serum tumor markers alone are insufficient for diagnosis or treatment decisions 1
2. Single-phase CT or MRI should not be used as diagnostic tools 1
3. Biopsy of potentially operable lesions should be avoided when possible due to risk of tumor seeding 1
4. Response assessment should be based on dynamic CT or MRI studies using modified RECIST criteria, not conventional RECIST 1
5. Cirrhosis due to vascular disorders (e.g., Budd-Chiari syndrome) or Fontan-associated liver disease may have benign hyperplastic nodules that mimic HCC on imaging 1