What does an elevated Carbohydrate Antigen 19-9 (CA 19-9) level indicate?

Elevated CA 19-9: Clinical Significance and Interpretation

An elevated CA 19-9 level primarily suggests pancreatic cancer but is not specific as it can be elevated in various other malignant and benign conditions, requiring confirmation with imaging studies and/or biopsy before making definitive conclusions. 1

What is CA 19-9?

• CA 19-9 is a tumor-associated antigen defined by a monoclonal antibody produced from murine spleen cells immunized with human colorectal cancer cell lines 1
• It exists in tissue as an epitope of sialylated Lewis A blood group antigen 1
• Approximately 5-10% of the population is genotypically Lewis ab-negative and cannot produce CA 19-9, making testing ineffective in these individuals 1, 2

Malignant Conditions Associated with Elevated CA 19-9

• Most commonly associated with pancreatic cancer, with highest levels typically seen in pancreatic malignancies 1, 3
• Can be elevated in other gastrointestinal tumors including:
  • Upper GI tract tumors 4
  • Colorectal cancer 4
  • Hepatocellular cancer 4
  • Ovarian cancer 4
  • Biliary tract cancer 2
  • Lung cancer 5

Benign Conditions Associated with Elevated CA 19-9

• Inflammatory conditions of the hepatobiliary system 4, 1
• Benign biliary obstruction 6, 3
• Thyroid disease 4
• Pneumonia and pleural effusion 5
• Renal failure 5
• Systemic lupus erythematosus (SLE) 5

Diagnostic Value

• Not recommended as a screening test for pancreatic cancer in asymptomatic individuals due to inadequate specificity and sensitivity 4, 1
• In symptomatic patients, CA 19-9 has a sensitivity of 79-81% and specificity of 82-90% for pancreatic cancer diagnosis 3, 7
• CA 19-9 levels are significantly lower in benign conditions compared to malignant conditions 8, 5

Prognostic Significance

• Pre-operative CA 19-9 levels provide important prognostic information:
  • Normal levels (<37 U/mL) are associated with prolonged median survival (32-36 months) 3, 7
  • Elevated levels (>37 U/mL) correlate with shorter survival (12-15 months) 3, 7
• CA 19-9 levels >100 U/mL may suggest unresectable or metastatic disease 3, 7
• Levels <100 U/mL imply likely resectable disease 3, 7

Monitoring Treatment Response

• CA 19-9 can be measured at the start of treatment for locally advanced or metastatic disease and every 1-3 months during active treatment 4, 1
• Normalization or decrease in CA 19-9 levels by ≥20-50% after surgery or chemotherapy is associated with prolonged survival 3, 7
• Rising CA 19-9 levels during treatment may indicate progressive disease, requiring confirmation with imaging studies 4, 1

Important Limitations

• False negative results in Lewis negative phenotype (5-10% of population) 3, 7
• Increased false positivity in the presence of obstructive jaundice (10-60%) 3, 7
• CA 19-9 determinations alone cannot provide definitive evidence of disease recurrence without confirmation by imaging studies and/or biopsy 4
• CA 19-9 testing alone is not recommended for determining operability of pancreatic cancer 4, 1

Clinical Approach to Elevated CA 19-9

• Interpret elevated CA 19-9 in the context of clinical presentation 5
• Consider both malignant and benign causes 8, 5
• Confirm abnormal results with appropriate imaging studies (CT, MRI, endoscopic ultrasound) and/or biopsy 4, 1
• Evaluate for biliary obstruction, which can cause false elevations 6, 3
• Consider other tumor markers like CEA for additional diagnostic information 8