CA 19-9: Reference Range, Interpretation, Collection And Panels

The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CA 19-9 for the diagnosis of pancreatic cancer is dependent on the cutoff level (see the table below). A normal level is less than 37 U/mL, which corresponds to a sensitivity of 81% (68%-93%), a specificity of 90% (76%-100%), a PPV of 72%, and a NPV of 96%. [1, 2] However, when CA 19-9 levels are greater than 1000 U/mL, sensitivity is 41%, specificity is 99.8%, PPV is 97%, and NPV is 89%.

Table. Cutoff levels of CA 19-9 for the Diagnosis of Pancreatic Cancer [2]

Table. (Open Table in a new window)

Cutoff (U/mL)	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)
37	81	90	72	96
100	68	98	87	94
300	54	99	92	91
1000	41	99.8	97	89

Elevated levels of CA 19-9 can be seen in healthy individuals. Elevated levels can also be seen in benign conditions, such as the following:

• Biliary tract obstruction [3]

• Cholangitis [4]

• Inflammatory bowel disease [5]

• Acute or chronic pancreatitis [6]

• Liver cirrhosis [7]

• Cystic fibrosis [8]

• Thyroid disease

Elevated levels of CA 19-9 can be seen in the following malignant conditions as well:

• Bile duct cancers [9]

• Colorectal cancers [10]

• Gastric cancers [11, 12]

• Ovarian cancers [13]

• Hepatocellular cancers [14]

• Esophageal cancers [15]

• Pancreatic cancers [16, 17, 18, 19]

Additionally, at least 5% of the population is unable to produce the CA 19-9 antigen. The overall low specificity and sensitivity of this assay precludes its use as a screening tool for pancreatic cancer. An elevated tumor marker level needs to be interpreted within the context of the patient’s history, physical examination, diagnostic imaging, and laboratory work-up findings.

High CA 19-9 levels (ie, greater than 1000 U/mL) correlate with unresectable or more advanced tumors, although this preoperative evaluation of CA 19-9 has not been widely used to establish inoperability. [20] High marker levels may also be used to predict patient outcomes. [21, 22] A decrease or normalization of CA 19-9 levels postoperatively correlates with a longer duration of survival. Conversely, rising marker levels postoperatively have been correlated with shorter duration of survival and increased disease recurrence.

Finally, CA 19-9 levels can be used to monitor tumor response to active treatment with surgery, with or without chemotherapy, radiation therapy, and/or other targeted or biological therapies. A decrease in CA 19-9 levels confirms the effectiveness of the therapeutic regimen, while a stable or rising level may indicate the need to change therapies.

A study by Ciprani et al indicated that in patients with an intraductal papillary mucinous neoplasm (IPMN), the invasive form of the condition is predicted when the serum CA 19-9 level is above 37 U/mL, as is the presence of concurrent pancreatic cancer and worse overall and disease-free survival. Among the study’s patients, who had IPMNs, 45.3% of those with preoperative CA 19-9 levels above 37 U/mL had the invasive disorder, compared with 18.0% of those with normal CA 19-9 levels. Moreover, concurrent pancreatic cancer was present in 17.2% of individuals with the higher CA 19-9 levels, compared with 4.9% of those with the lower ones. [23]