Monitoring with chromogranin A

"With chromogranin A... you may see elevated levels several weeks or a few months before you see changes reflecting tumor growth on the CT scan or the MRI." —Dr Larry Kvols

A useful role in managing patients with NETs

Blood levels of chromogranin A (CgA) are elevated in up to 90% of patients with NETs,1,2 with levels that are independent of hormone secretion.2,3 In patients with existing NETs, CgA levels may be associated with neoplasm location, burden, and degree of differentiation.4

Some types of NETs, however, express lower levels of CgA than others, so test results should be interpreted with caution. Well-differentiated NET cells, for example, frequently express CgA while poorly differentiated neuroendocrine carcinoma cells generally do not.4 CgA also may not be the most reliable indicator of lung NETs and functional pancreatic NETs, such as benign insulinomas.5,6

Conversely, CgA levels seem to be highest in ileal NETs, and GI and pancreatic NETs associated with MEN-1 syndrome.4 Across all types of NETs, CgA levels typically are higher with extensive metastases than with local or regional disease, and are moderately higher in the presence of hepatic metastases.4 As such, CgA levels can also be used to help monitor disease response and progression.7

When monitoring a NET, CgA may be an earlier indicator of disease progression than radiologic studies,7 which may still indicate unchanged tumor volume.8 Elevated CgA levels may also be an early indicator of recurrence in patients with resected NETs.9

In terms of correlation to burden, CgA levels are typically highest in metastatic disease, particularly in patients with multiple liver metastases.2,9

For continued disease management, preliminary biomarkers results should be confirmed with other appropriate techniques, such as imaging (eg CT and MRI).12

CgA testing is available through most hospitals and commercial pathology labs

Several commercially available assays measure CgA levels.11

NOTE: When administering CgA tests, clinicians should keep in mind that tests are not standardized, and results may vary among laboratories and assays.11 Certain therapies can increase CgA levels without the presence of a NET, notably proton pump inhibitors.18,19 Some conditions can also increase CgA levels—chronic atrophic gastritis, renal or hepatic dysfunction, and arterial hypertension, for example.18,19

It is also important to note that CgA is not universally used in the medical community because of these limitations and because some doctors do not believe that test results affect choices in the course of therapy.20

For diagnostic accuracy—as well as continued disease management—preliminary biomarker results should be confirmed with appropriate imaging and/or endoscopic techniques, as well as biopsy.21