What is the significance of elevated Carbohydrate Antigen 19-9 (CA19-9) tumor markers?

From the Guidelines

Elevated Carbohydrate Antigen 19-9 (CA19-9) tumor markers are significant in monitoring pancreatic cancer and potentially guiding treatment decisions, but their utility is limited by variability in sensitivity and specificity, and they should not be used as a screening test for the general population. For patients with known pancreatic cancer, I recommend checking CA19-9 levels before treatment begins to establish a baseline, then periodically during treatment (typically every 1-3 months) to assess treatment response, as supported by the European Society for Medical Oncology clinical practice guidelines 1. After treatment completion, monitoring should continue every 3-6 months for at least 2 years to detect potential recurrence. The test requires a simple blood draw and no special preparation. However, it's essential to understand that CA19-9 is not recommended as a screening test for the general population due to limited sensitivity and specificity, with about 5-10% of people unable to produce elevated CA19-9 even with cancer present, and levels can be falsely elevated in benign conditions like pancreatitis, liver disease, and gallstones, as noted in the study by the American Hepato-Pancreato-Biliary Association 1.

Some key points to consider when interpreting CA19-9 levels include:

• CA19-9 is the most useful tumor marker in pancreatic cancer, but its levels can be influenced by the presence of the Lewis blood group antigen, with approximately 7-10% of the population lacking this antigen and thus unable to produce CA19-9 1.
• A preoperative serum CA19-9 level ≥500 UI/ml clearly indicates a worse prognosis after surgery, highlighting the importance of considering CA19-9 levels in the context of overall patient management 1.
• The combination of serum tumor markers, such as CA19-9, and imaging studies, like MRI/MRCP, can improve the sensitivity and specificity of diagnosing hepatobiliary malignancies in patients with primary sclerosing cholangitis, as demonstrated in the study by the European Society of Gastrointestinal Endoscopy and European Association for the Study of the Liver 1.
• CA19-9 levels should be interpreted with caution, considering the potential for false positives and false negatives, and in the context of other diagnostic tools, such as imaging and histological examination, as emphasized in the clinical practice guidelines by the European Society for Medical Oncology 1.

In clinical practice, CA19-9 is most valuable when tracking trends over time rather than focusing on a single value, as rising levels may indicate disease progression while falling levels may suggest treatment effectiveness. Therefore, regular monitoring of CA19-9 levels, in conjunction with other diagnostic tools and clinical assessment, is crucial for optimal management of patients with pancreatic cancer.

From the Research

Significance of Elevated CA19-9 Tumor Markers

• Elevated Carbohydrate Antigen 19-9 (CA19-9) tumor markers are significant in the diagnosis and monitoring of pancreatic cancer, as they are the most commonly used and best validated serum tumor marker for this disease 2, 3.
• CA19-9 is normally synthesized by normal human pancreatic and biliary ductal cells, and its levels can be overexpressed in several benign gastrointestinal disorders, but it exhibits a dramatic increase in its plasmatic levels during neoplastic disease 2.
• The sensitivity and specificity of CA19-9 for the diagnosis of pancreatic cancer in symptomatic patients are 79-81% and 82-90%, respectively 3.
• Elevated CA19-9 levels are associated with poor prognosis, and pre-operative CA19-9 serum levels can provide useful prognostic information, with patients having normal CA19-9 serum levels (<37 U/ml) having a prolonged median survival compared to those with elevated CA19-9 serum levels (>37 U/ml) 3, 4.
• A CA19-9 serum level of <100 U/ml implies likely resectable disease, whereas levels >100 U/ml may suggest unresectability or metastatic disease 3.
• Normalization or a decrease in post-operative CA19-9 serum levels by ≥20-50% from baseline following surgical resection or chemotherapy is associated with prolonged survival compared to failure of CA19-9 serum levels to normalize or an increase 3, 5.

Limitations of CA19-9 as a Biomarker

• CA19-9 has several limitations, including false negative results in subjects with Lewis (a-b-) genotype and false positive elevation in patients with benign diseases, which do not make it a good cancer-specific marker and render it impotent as a screening tool 2, 3.
• CA19-9 can be expressed in several benign and malignant diseases, and its levels can be influenced by various factors, such as obstructive jaundice, which can lead to increased false positivity 3, 6.

Clinical Use of CA19-9

• CA19-9 is widely used in clinical practice for the diagnosis, staging, and monitoring of pancreatic cancer, despite its limitations 2, 3, 4.
• The measurement of CA19-9 levels can provide important information regarding prognosis, overall survival, and response to chemotherapy, as well as predict post-operative recurrence 3, 6, 5.
• The normalization of CA19-9 levels following neoadjuvant therapy is a strong prognostic marker for long-term survival in patients with localized pancreatic cancer 5.