Serum CA 19-9 as a Biomarker for Pancreatic Cancer—A Comprehensive Review

Pancreatic cancer is an aggressive tumor with a dismal prognosis, biomarkers that can detect tumor in its early stages when it may be amenable to curative resection may improve prognosis. At present, serum CA 19-9 is the only validated tumor marker in widespread clinical use, but precise knowledge of its role in pancreatic cancer diagnosis, staging, determining resectability, response to chemotherapy and prognosis remains limited. A comprehensive search was performed using PubMed with keywords “pancreatic cancer” “tumor markers” “CA 19-9” “diagnosis” “screening” “prognosis” “resectability” and “recurrence”. All English language articles pertaining to the role of CA 19-9 in pancreatic cancer were critically analyzed to determine its utility as a biomarker for pancreatic cancer. Serum CA 19-9 is the most extensively studied and clinically useful biomarker for pancreatic cancer. Unfortunately, CA 19-9 serum level evaluation in pancreatic cancer patients is limited by poor sensitivity, false negative results in Lewis negative phenotype (5–10%) and increased false positivity in the presence of obstructive jaundice (10–60%). Serum CA 19-9 level has no role in screening asymptomatic populations, and has a sensitivity and specificity of 79–81% and 82–90% respectively for the diagnosis of pancreatic cancer in symptomatic patients. Pre-operative CA 19-9 serum level provide useful prognostic information as patients with normal CA 19-9 serum levels (<37 U/ml) have a prolonged median survival (32–36 months) compared to patients with elevated CA 19-9 serum levels (>37 U/ml) (12–15 months). A CA 19-9 serum level of <100 U/ml implies likely resectable disease whereas levels >100 U/ml may suggest unresectablity or metastatic disease. Normalization or a decrease in post-operative CA 19-9 serum levels by ≥20–50% from baseline following surgical resection or chemotherapy is associated with prolonged survival compared to failure of CA 19-9 serum levels to normalize or an increase. Carbohydrate antigen (CA 19-9) is the most extensively studied and validated serum biomarker for the diagnosis of pancreatic cancer in symptomatic patients. The CA 19-9 serum level can provide important information with regards to prognosis, overall survival, and response to chemotherapy as well as predict post-operative recurrence. Non-specific expression in several benign and malignant diseases, false negative results in Lewis negative genotype and an increased false positive results in the presence of obstructive jaundice severely limit the universal applicability of serum CA 19-9 levels in pancreatic cancer management.