Germline MEN1 testing patterns in patients with neuroendocrine tumors: A 12-year retrospective analysis within...

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant tumor predisposition syndrome in which neuroendocrine tumors (NET) represent a major driver of morbidity and mortality. Timely recognition of MEN1 after NET diagnosis enables syndrome-specific surveillance and cascade testing, yet real-world evidence on MEN1 testing implementation in oncology pathways remains limited. The aim of this study was to evaluate MEN1 testing practices and assess concordance with guideline-based indications and nomogram-predicted risk. A retrospective cohort study was performed within NETwerk, a Belgian ENETS CoE, with patients <70 years diagnosed between 2012 and 2024 with pancreatic, pulmonary, gastric, or thymic well-differentiated NET. MEN1 testing data were extracted from medical records. In patients without a prior MEN1 diagnosis at NET presentation, guideline-based indications for MEN1 testing were assessed and compared with observed testing. Additionally, nomogram-predicted MEN1 risk was estimated, using a ≥5% threshold for descriptive risk stratification, and overlap between guideline- and nomogram-based indications was described. In 267 patients without prior MEN1 diagnosis, MEN1 testing was performed in 42 (15.7%), mainly in patients ≤50 years. Including 21 patients with MEN1 diagnosis before NET development, overall MEN1 prevalence was 10.4%. In patients without a prior MEN1 diagnosis at NET presentation, guideline-based indications showed moderate agreement with observed testing (κ = 0.50, p <.001) without directional bias toward over- or undertesting, with undertesting most evident in MEN1-suspicious tumor presentations (gastrinoma, early-onset panNET, thymic NET). Among patients tested despite lacking guideline indications (n = 20), none had MEN1. Application of the nomogram yielded an exact risk score for 77 patients and a risk score range for the remaining 190 patients due to incomplete phenotyping. In the patients with complete phenotyping, median predicted MEN1 risk was 3.3% (IQR 2.4-4.3). Testing rate increased with higher predicted risk: 85.7% (12/14) for ≥5% underwent testing vs. 23.8% (15/63) for <5%. Guideline- and nomogram-based stratification overlapped in most patients. In conclusion, this retrospective cohort study shows that MEN1 testing after NET diagnosis showed moderate alignment with guideline-based indications and was constrained by incomplete risk capture and phenotyping. Embedding a standardized MEN1 risk checklist and minimal endocrine phenotyping into NET MDT workflows, supported by quantitative risk estimation in selected cases, may improve guideline-concordant MEN1 detection and downstream benefits for patients and their relatives.