Prospective study of chromogranin A as a predictor of progression in patients with pancreatic, small intestinal and unknown primary neuroendocrine tumors.

Background Retrospective studies are conflicting but most report that an increase in plasma chromogranin A (CgA) predicts tumor progression in neuroendocrine tumor (NET) patients. Prospectively we investigated if changes in plasma CgA was associated with tumor burden changes in NET patients with disseminated disease. Methods We included 239 patients from five NET centers between 2010-2013. CgA was measured within six weeks of a CT or an MRI in a patient undergoing at least two scan examinations performed with 1-24 months interval. In a post-hoc analysis, CgA measured 3-6 month prior to the CT/MRI was analyzed. Changes in tumor size were evaluated by RECIST1.1. A 25% change in CgA was chosen to discriminate between increased, decreased or unchanged levels. Results In 671 events (2 CT/MRI scans and 2 corresponding CgA measurements) we found a weak positive correlation between the RECIST 1.1 responses and change in plasma CgA from baseline (Spearman’s rank correlation coefficient: 0.15; p<0.05). Of 304 events in the post-hoc analysis, 58 showed progression, 228 stable disease, and 18 regression with a median change in CgA +19%(IQR:57-(-20)), -12%(+23-(-38)) and -73%(-55-(-83)), respectively. The correlation coefficients for all sites were 0.17(p=0.003); and 0.16(p=0.07), 0.18(p=0.04); and 0.20(p=0.21) for small intestinal (n=137), pancreatic (n=123) and unknown primary NET (n=40), respectively. In the 58 events showing tumor progression, sensitivity and specificity of an increased CgA concentration were 36% and 82% with positive and negative predictive values of 32% and 85%. Conclusions In this prospective study of GEP-NET patients we observed only a weak association between change in plasma CgA and change in tumor burden. CgA as a single biomarker was thus inadequate to predict tumor progression.