What are the initial steps in the workup of liver cancer?

Initial Workup of Liver Cancer

The initial workup of suspected liver cancer should include a comprehensive diagnostic evaluation consisting of history and clinical examination, laboratory analysis, imaging studies, and assessment of portal hypertension as outlined in the ESMO-ESDO clinical practice guidelines 1.

Clinical Assessment

• History and clinical examination:
  • Risk factors for chronic liver disease: IV drug use, alcohol intake 1
  • Symptoms and signs of chronic liver disease: jaundice, ascites, encephalopathy, splenomegaly 1
  • Performance status and nutritional state 1

Laboratory Analysis

• Etiology of liver disease:

  • Hepatitis B and C viral markers (HBsAg, HBV DNA, HCV antibodies) 1
  • Iron status (for hemochromatosis) 1
  • Autoimmune markers 1

• Liver function assessment:

  • Prothrombin time, albumin, bilirubin 1
  • Platelets 1

• Tumor marker:

  • Serum alpha-fetoprotein (AFP) - though elevated in only 50-75% of cases 1

Imaging Studies

• Initial imaging:

  • Dynamic (multiple phase) MRI or CT studies for diagnosis and evaluation of tumor extent 1
  • These should assess: number and size of nodules, vascular invasion, extrahepatic spread 1

• Diagnostic algorithm based on nodule size in cirrhotic patients:

  • Nodules <1 cm: Follow with ultrasound at 3-6 month intervals 1
  • Nodules 1-2 cm: Investigate with at least two dynamic studies (triphasic CT, contrast ultrasound, or MRI) 1
  • Nodules >2 cm with typical HCC features on dynamic imaging or any nodule with AFP >400 ng/ml: Consider as proven HCC without need for biopsy 1

• Additional imaging for staging:

  • Chest CT to evaluate for metastases 1
  • Bone scan in advanced disease or transplant candidates 1

Assessment of Portal Hypertension

• Upper endoscopy:

  • To identify varices and/or hypertensive gastropathy 1

• Optional:

  • Transjugular measurement of hepatic-venous pressure gradient 1

Pathological Diagnosis

• When to perform biopsy:
  • Biopsy is rarely required if imaging is characteristic in cirrhotic patients 1
  • Biopsy should be avoided in potentially operable lesions due to 1-3% risk of tumor seeding 1
  • Required for diagnosis in non-cirrhotic patients or when imaging is inconclusive 1

Staging and Risk Assessment

• Staging systems:
  • TNM/AJCC staging criteria should be used 1
  • Barcelona Clinic Liver Cancer (BCLC) staging is recommended for patients with underlying cirrhosis 1
  • Child-Pugh score to assess liver function 1, 2

Important Considerations and Pitfalls

1. Surveillance context:

   • Most cases of liver cancer are diagnosed through surveillance in high-risk patients (cirrhosis, chronic HBV/HCV) 1
   • Surveillance should be performed using ultrasound every 6 months in high-risk patients 1, 2

2. Non-invasive diagnosis criteria:

   • Non-invasive diagnosis is only possible in cirrhotic patients 1
   • Requires identification of typical vascular hallmark (hypervascular in arterial phase with washout in portal venous or delayed phases) 1

3. Biopsy considerations:

   • Avoid biopsy in patients who are not candidates for therapy due to serious comorbidity 1
   • Avoid in decompensated cirrhosis patients on transplant waiting list 1
   • Avoid in candidates for resection with acceptable surgical risk 1

4. Etiology awareness:

   • While HBV and HCV are the most common causes globally, alcoholic and non-alcoholic fatty liver disease are increasingly important etiologies 1, 3, 4
   • Understanding etiology helps guide subsequent management 1

By following this systematic approach to the initial workup of liver cancer, clinicians can establish diagnosis, determine disease extent, assess liver function, and gather the necessary information to guide treatment decisions that will impact patient morbidity, mortality, and quality of life.