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 an NPV of 96%. [2, 3] 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 1).

Table 1. Cutoff Levels of CA 19-9 for the Diagnosis of Pancreatic Cancer [3]

(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 [4]
• Cholangitis [5]
• Inflammatory Bowel Disease [6]
• Acute or chronic pancreatitis [7]
• Liver cirrhosis [8, 9]
• Cystic fibrosis [10]
• Thyroid disease

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

• Bile duct cancers [11]
• Colorectal cancers [12]
• Gastric Cancer [13, 14]
• Ovarian Cancer [15]
• Hepatocellular cancers [16]
• Esophageal Cancer [17]
• Pancreatic Cancer [18, 19, 20, 21]

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 workup findings.

In a prospective study of patients with locally advanced pancreatic cancer (LAPC), researchers investigated the value of CA 19-9 as a prognostic and predictive marker. They found that a significant drop in CA 19-9 levels after initial chemotherapy was a strong indicator of both improved overall survival and the ability to undergo a successful R0 resection (complete tumor removal). Patients whose CA 19-9 levels did not decrease had no chance of a successful resection. The study concluded that monitoring CA 19-9 response is a valuable tool to select patients with LAPC who may benefit from surgery. [22] High CA 19-9 levels (i.e., > 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. [23] High marker levels may also be used to predict patient outcomes. [24, 25] 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 a 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 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 higher CA 19-9 levels, compared with 4.9% of those with the lower ones. [26]

In patients with IPMNs, a serum CA 19-9 level > 37 U/mL serves as a predictor of invasive transformation and the presence of concurrent pancreatic cancer. Studies have indicated that patients with IPMNs and elevated CA 19-9 levels have a significantly higher incidence of invasive disease and worse survival rates. The ability to discriminate between pancreatic ductal adenocarcinoma and IPMNs can be improved by combining CA 19-9 with other markers such as CA-125. [27]

A decline or normalization of CA 19-9 following surgery is associated with longer survival. Conversely, a postoperative rise is a strong indicator of recurrence. Notably, a dynamic increase in CA 19-9 levels can predict recurrence with high accuracy, often preceding detection by imaging. For instance, a 2.45-fold increase in the postoperative CA 19-9 levels has been shown to predict recurrence with approximately 83-90% specificity and 90% sensitivity. [28]