What are the next steps for a patient with elevated Carbohydrate Antigen 19-9 (CA 19-9) levels?

Next Steps for a Patient with Elevated CA 19-9 Levels

For patients with elevated CA 19-9 levels, comprehensive imaging studies including MRI with MRCP and thoraco-abdomino-pelvic CT should be performed to investigate for potential pancreaticobiliary malignancies, followed by tissue biopsy if lesions are identified. 1

Understanding CA 19-9 Limitations

• CA 19-9 is a nonspecific tumor marker that can be elevated in:

  • Pancreatic cancer (most common association)
  • Other gastrointestinal malignancies (colorectal, hepatocellular, biliary tract)
  • Ovarian cancer
  • Benign conditions (biliary obstruction, inflammatory conditions of hepatobiliary system)
  • Thyroid disease and other benign conditions 1

• Important considerations:

  • Approximately 5-10% of the population is Lewis blood group antigen-negative and cannot produce CA 19-9, making the test invalid in these individuals 1
  • CA 19-9 lacks adequate specificity and sensitivity for cancer screening 1
  • Small pancreatic tumors may not cause CA 19-9 elevation 1

Diagnostic Workup

1. Imaging studies:

   • MRI with MRCP (magnetic resonance cholangiopancreatography) - reference examination for local extension of pancreatic/distal cholangiocarcinoma and hepatic metastases 1
   • Thoraco-abdomino-pelvic CT scan - reference examination for lymph node and metastatic extension 1
   • Consider FDG-PET for identification of nodal metastases, distant metastases, and disease recurrence (not recommended for primary diagnosis) 1

2. Tissue sampling if lesions identified:

   • Core biopsy for diagnostic pathology and molecular profiling 1
   • For distal/perihilar cholangiocarcinoma without extraductal metastasis, PTC or ERCP-guided biopsies 1
   • EUS-guided FNA or FNB for enlarged regional nodes or if ERCP-guided biopsies are negative/inconclusive 1

3. Laboratory testing:

   • Liver function tests to assess biliary obstruction 1
   • Consider testing for other tumor markers based on clinical suspicion

Management Considerations

• Markedly elevated CA 19-9 levels are associated with poorer prognosis in biliary tract cancers 1
• CA 19-9 can be useful for monitoring treatment response 1
• For patients with resectable pancreatic lesions, preoperative CA 19-9 levels may help predict outcomes, but should not be used alone to determine operability 1
• In post-operative patients, rising CA 19-9 levels may predict recurrent disease, but confirmation with imaging studies and/or biopsy is necessary 1

Important Clinical Pearls

• Even extremely high CA 19-9 levels (in the thousands) can occasionally be seen in benign conditions such as xanthogranulomatous cholecystitis 2
• In patients with elevated CA 19-9 but no obvious cause, follow-up is warranted as causative conditions (including cancers and benign tumors) may be detected during the follow-up period 3
• Consider non-malignant causes of CA 19-9 elevation, including delayed radiation-induced inflammation in patients with history of radiation therapy 4