Tumor Marker CA 19-9 for Assessing Pancreatic Cancer Response

Each year, over 45,000 people in the United States are diagnosed with pancreatic cancer, representing approximately 3% of all newly diagnosed cancers.¹ Pancreatic cancer is also the fourth leading cause of cancer death.¹ The diagnosis and treatment of pancreatic cancer can be challenging to both patients and health care professionals. To confirm a diagnosis and assess treatment response, one of the most commonly used tumor markers to is serum CA 19-9. Although it is frequently used, it should only be ordered when clinically indicated.

When ordering a serum CA 19-9 level, it is important to keep in mind its sensitivity and specificity. According to an extensive review of the literature, the sensitivity of CA 19-9 was between 79% and 81%, and its specificity was 82% to 90% in patients who are symptomatic on presentation.² Patients with newly diagnosed pancreatic cancer may present with weight loss, painless jaundice, and epigastric abdominal pain that radiates to the back, among other symptoms. CA 19-9 has a low positive predictive value (between 0.5% and 0.9%), therefore, it has limited utility as a screening test.² Furthermore, a patient must have the Lewis blood group antigen—present in approximately 90% to 95% of the population—in order to express CA 19-9, therefore, it would not be useful in the remaining 5% to 10% of the population.²

Once formally diagnosed with pancreatic cancer, the absolute value of CA 19-9 prior to surgical intervention can provide information on the patient’s prognosis. Levels greater than 100 IU/mL are typically not resectable and may be indicative of metastatic disease; on the other hand, levels lower than 100 IU/mL are usually consistent with resectability.² Patients with pancreatic cancer who have normal levels (< 37 IU/mL) have a longer median survival (32-36 months) when compared with patients with CA-19-9 levels above 37 IU/mL (12-15 months).²

After chemotherapy and/or surgery, it is important to trend the CA 19-9 levels in order to monitor response to therapy. Prolonged survival is associated with CA 19-9 levels that decrease by 20% to 50% from their baseline level within 6 to 8 weeks of treatment.²

There are additional clinical scenarios that may complicate the interpretation of an elevated CA 19-9, including obstructive jaundice, cirrhosis, cholangitis, and other gastrointestinal (GI) cancers.² GI cancers that can also have elevated CA 19-9 levels include cholangiocarcinoma, as well as gallbladder, hepatocellular, gastric, and colorectal cancer.

Based on the aforementioned issues with using CA 19-9 in certain clinical situations, there is accumulating data on additional laboratory tests that may aid in the diagnosis and treatment of pancreatic cancer. Samples from a patient’s stool, salivary glands, and pancreatic enzymes have provided some data that may prove useful in the future.³ Although some of the preliminary data is promising, the collection of such samples may provide a challenge and barrier to their routine use, as opposed to a simpler blood test, such as CA 19-9.

Biomarkers represent an increasingly popular area of research, particularly in the area of oncology. In addition to monitoring CA 19-9 levels, other biomarkers such as macrophage inhibitory cytokine-1 (MIC-1), carcinoembryonic antigen cellular adhesion molecule-1 (CEACAM-1), mucins, matrix metalloproteinase (MMP), tissue polypeptide-specific antigen (TPS), and regenerating gene family member 4 (REG-4) may one day prove to be clinically relevant and useful.³ Before these tests become routine orders, more research is needed in order to further define how these biomarkers can help guide the management of the patient’s cancer.

When performing a work-up for pancreatic cancer, clinical judgment should be used when deciding on blood tests and imaging. CA 19-9 is an important tumor marker that can help guide the diagnosis and treatment of pancreatic cancer; however, it is always important to consider how a specific test will be used to change medical management for a patient prior to ordering it.

References

1. Siegel R, Naishadham D, Jemal A. Cancer Statistics, 2013. CA Cancer J Clin. 2013;63(1):11-30.
2. Ballehaninna UK, Chamberlain RS. Biomarkers for pancreatic cancer: promising new markers and options beyond CA 19-9. Tumour Biol. 2013;34(6):3279-3292.92.
3. Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal. J Gastrointest Oncol. 2012;3(2):105-119.