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 and histology negative (IND) (n=106), and image negative and histology positive (n=29). CgA metrics: NEOLISA, ULN: 108ng/mL, DD: ULN: 99ng/mL. Data: mean ±SEM. 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 versus 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.