NETest is superior to chromogranin A in neuroendocrine neoplasia: a prospective ENETS CoE analysis.

Introduction The absence of a reliable, universal biomarker is a significant limitation in neuroendocrine neoplasia (NEN) management. We prospectively evaluated two CgA assays, (NEOLISA, EuroDiagnostica) and (CgA ELISA, Demeditec Diagnostics (DD)) and compared the results to the NETest. Methods NEN cohort (n = 258): pancreatic, n = 67; small intestine, n = 40; appendiceal, n = 10; rectal, n = 45; duodenal, n = 9; gastric, n = 44; lung, n = 43. Image-positive disease (IPD) (n = 123), image & histology- negative (IND) (n = 106), and image-negative and histology positive (n = 29). CgA metrics: NEOLISA, ULN: 108 ng/mL, DD: ULN: 99 ng/mL. Data mean ± s.e.m. NETest: qRT-PCR – multianalyte analyses, ULN: 20. All samples de-identified and assessed blinded. Statistics: Mann–Whitney U-test, Pearson correlation and McNemar-test. Results CgA positive in 53/258 (NEOLISA), 32 (DD) and NETest-positive in 157/258. In image- positive disease (IPD, n = 123), NEOLISA-positive: 33% and DD: 19%. NETest-positive: 122/123 (99%; McNemar’s Chi2= 79–97, P < 0.0001). NEOLISA was more accurate than DD (P = 0.0003). In image- negative disease (IND), CgA was NEOLISA-positive (11%), DD (8%), P = NS, and NETest (33%). CgA assays could not distinguish progressive (PD) from stable disease (SD) or localized from metastatic disease (MD). NETest was significantly higher in PD (47 ± 5) than SD (29 ± 1, P = 0.0009). NETest levels in MD (35 ± 2) were elevated vs localized disease (24 ± 1.3, P = 0.008). Conclusions NETest, a multigenomic mRNA biomarker, was ~99% accurate in the identification of NEN disease. The CgA assays detected NEN disease in 19–33%. Multigenomic blood analysis using NETest is more accurate than CgA and should be considered the biomarker standard of care.