Clinical Value of a 51-Neuroendocrine Tumor-Specific Gene Signature (NETest 2.0) for Management of Pancreatic and Small Bowel Neuroendocrine Tumors: A Prospective Study in a Consecutive Cohort of 82 Patients Considered for Surgery.

OBJECTIVES: To prospectively evaluate the clinical utility of NETest2.0, a 51-neuroendocrine tumor (NET)-specific gene whole blood assay (NETest2.0) for monitoring surgical patients with gastroenteropancreatic NETs (GEPNET). BACKGROUND: GEPNETs are challenging regarding postoperative surveillance and monitoring for recurrence or progression. METHODS: Blood samples were collected at baseline and during follow-up, and NETest2.0 was measured (scored 0-100; cutoff normal: <50) in 82 consecutive patients with GEPNET. Scores were correlated with follow-up and disease status, including no evidence of disease, stable disease, recurrent disease, and progressive disease. RESULTS: Pancreatic NET (n = 29): median age, 57 (26-81) years, M:F (17:12), G1: 19, G2: 8, G3: 2, stages I to III (n = 18), and stage IV (n = 11). Median follow-up, 122 (4-163) months; 7 (24%) died. NETest2.0 correlated with outcomes and was significantly higher in those who died (P = 0.0215). Small bowel NET (n = 53): median age, 66 (36-86) years, M:F (22:31), G1: 45, G2: 8, G3: 0, stages I to III (n = 25), and stage IV (n = 28). Median follow-up, 83 (12-157) months; thirteen (25%) died. NETest2.0 correlated with outcomes and was significantly higher in those who died (P = 0.0011). Scores ≥50 were significantly associated with recurrent disease (P = 0.0013). Scores ≥65 were associated with progression and poorer overall survival. CONCLUSIONS: NETest2.0 accurately identified disease status and correlated with clinical outcomes. Patients were stratified into molecular remission, stable disease, and high-risk progression states. Low scores (<50) identified surgical patients unlikely to recur; scores ≥65 identified individuals at increased risk for progression.