Circulating biomarkers in the diagnosis and management of neuroendocrine neoplasms

Neuroendocrine neoplasms (NENs) comprise a broad family of tumours arising from the diffuse neuroendocrine system and endocrine glands, and vary widely in clinical behaviour ranging from indolent to highly aggressive. Established monoanalyte biomarkers including chromogranin A and NEN-derived hormones have clinical utility but some major limitations including non-specificity for tumour origin, variable sensitivity between NEN subtypes, inconsistent correlation with prognostic factors including metastasis, and can be falsely elevated in common non-NEN pathologies. The expansion of investigative NEN biomarkers through advancing omics technologies and computational methods holds potential to improve diagnosis, prognostication and aid therapy selection or trial allocation. This review will outline established and evolving NEN circulating biomarkers, and their roles in clinical practice.