Prognostic significance of Chromogranin A in small pancreatic neuroendocrine tumors

Background: The incidence of nonfunctional pancreatic neuroendocrine tumors ≤2cm is rising. The biologic behavior of these tumors is variable; thus, their management remains controversial. Chromogranin A upregulation is a useful diagnostic biomarker of neuroendocrine tumors; however, the prognostic significance of Chromogranin A is unclear. The objective of this study was to determine whether Chromogranin A levels have prognostic value in pancreatic neuroendocrine tumor patients and may help guide management.

Methods: We evaluated the National Cancer Database over a 10-year period (2004-2013). Patients with pancreatic neuroendocrine tumors measuring ≤2cm, without distant metastases, were identified and categorized as Chromogranin A high (>420ng/mL) or Chromogranin A low (≤420ng/mL), and those lacking data on Chromogranin A levels were excluded from the study. Univariate and multivariate analyses were performed using Cox proportional hazards model. Cut-point determination was performed using the Contal and O'Quigley method.

Results: Of the 445 eligible patients, 352 (79%) were Chromogranin A low and 93 (21%) were Chromogranin A high. Median Chromogranin A level was 71ng/mL (interquartile range, 24-294ng/mL). Chromogranin levels were associated with clinical nodal status and grade. Furthermore, on multivariate analysis, Chromogranin A levels (Chromogranin A high versus Chromogranin A low) independently predicted overall survival after controlling for tumor size, grade, clinical nodal status, and academic status of the facility (hazard ratio: 7.90, 95%CI: 2.34-26.69, P = .001). The greatest benefit of surgical resection was noted in patients in the Chromogranin A high subgroup (log-rank P <.001).

Conclusion: Serum Chromogranin A levels can be incorporated in surgical decision-making for patients with small pancreatic neuroendocrine tumors. Patients in the Chromogranin A low group can be considered for observation, whereas patients in the Chromogranin A high group should be strongly considered for resection.