The Role of Liquid Biopsy in Gastroenteropancreatic Neuroendocrine Neoplasms

Simple Summary Neuroendocrine neoplasms, primarily found in the gastroenteropancreatic tract, are classified as neuroendocrine tumours and neuroendocrine carcinomas, depending on the grade. Liquid biopsy offers a less invasive alternative to tissue biopsy in detecting circulating tumour components in body fluids. This systematic review evaluates liquid biopsy applications in neuroendocrine neoplasms, approaching its various types in different settings, such as diagnosis and characterisation; prognostic and predictive value; monitoring treatment response and prediction of recurrence; and finally, current applications and future perspectives. Overall, liquid biopsy holds potential for managing neuroendocrine neoplasms, and its use should be standardised.Abstract Neuroendocrine neoplasms incidence has been increasing, arising the need for precise and early diagnostic tools. Liquid biopsy (LB) offers a less invasive alternative to tissue biopsy, providing real-time molecular information from circulating tumour components in body fluids. The aim of this review is to analyse the current evidence concerning LB in NENs and its role in clinical practice. We conducted a systematic review in July 2024 focusing on LB applications in NENs, including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), micro RNA (miRNA), messenger RNA (mRNA) and extracellular vesicles. Sixty-five relevant articles were analysed. The LB showed potential in diagnosing and monitoring NENs. While CTCs face limitations due to low shedding, ctDNA provides valuable information on high-grade neoplasms. MiRNA and mRNA (e.g., the NETest) offer high sensitivity and specificity for diagnosis and prognosis, outperforming traditional markers like chromogranin A. The LB has significant potential for NEN diagnosis and monitoring but lacks widespread clinical integration due to limited prospective studies and guidelines, requiring further validation. Advances in sequencing technologies may enhance the clinical utility of LB in NENs. Future research should focus on refining LB methods, standardising protocols and exploring applications in high-grade NENs.