Endoscopic Ultrasound for the Management of Pancreatic Neuroendocrine Tumors: Diagnosis, Treatment, and Future Perspectives

Pancreatic neuroendocrine tumors (PanNETs) are increasingly diagnosed, reflecting greater clinical awareness, improved imaging, and revised classification. This review summarizes evidence on epidemiology, diagnostic workup, and endoscopic ultrasound (EUS)-guided management of PanNETs, encompassing diagnostic evaluation, tissue acquisition, and therapeutic interventions. EUS provides the highest diagnostic yield for lesions < 20 mm and enables detailed morphologic and vascular assessment through contrast-enhanced and harmonic EUS, quantitative elastography, and, in selected cases, needle-based confocal laser endomicroscopy. Fine-needle biopsy is superior to fine-needle aspiration for specimen adequacy, immunohistochemistry, and Ki-67 assessment, but preoperative grading may still be underestimated, with direct impact on decisions between surveillance, surgery, and systemic therapy. Therapeutically, EUS-guided radiofrequency ablation achieves high short-term to midterm clinical and radiologic control in insulinomas ≤ 2 cm and in selected small nonfunctioning PanNETs, at the cost of adverse event rates around 15%-20%. Ethanol and microwave ablation are feasible but supported by less mature data, and all EUS-guided ablation strategies should currently be regarded as investigational, pending long-term comparative studies versus surgery and active surveillance. In borderline or locally advanced disease, neoadjuvant [¹⁷⁷Lu]-Lu-DOTATATE appears to facilitate resection, but its optimal role remains to be defined. Emerging artificial intelligence and radiomics models using EUS images may refine risk stratification and support a precision endoscopy paradigm in PanNETs.