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Emerging Diagnostics and Therapies in Neuroendocrine Neoplasms: A Critical Review

J. Hernandez-Felix,M. Meneses-Medina,R. Riechelmann,J. Strosberg,Rocio Garcia-Carbonero,J. Rivero

Published 2025 in Cancers

ABSTRACT

Simple Summary Neuroendocrine neoplasms are uncommon cancers that arise from hormone-producing cells and can appear in many organs, making them difficult to diagnose and treat. Over the past few years, major advances have emerged in specialized imaging, blood-based molecular diagnostics, and targeted therapies such as cabozantinib and belzutifan. Novel radioactive agents, cell-based treatments, and immunotherapeutic approaches are progressing swiftly from research settings into clinical trial phases. Given the wide array of sources reporting these advancements, healthcare professionals and researchers may find it challenging to stay informed about the latest evidence. We review the most important developments up to mid-2025, discuss how each innovation enhances diagnostic and treatment capabilities, and outline ongoing studies that hold promise for further advancing patient care. Abstract Neuroendocrine neoplasms (NENs) are biologically diverse tumors. This article is a critical review of recent evidence focusing on systemic therapies (through mid-2025). We summarize what is most practice-relevant and where gaps remain. In diagnosis, somatostatin-receptor PET/CT has largely replaced older scintigraphy, and adding FDG PET can flag more aggressive disease. Blood-based tests and selected tissue markers (e.g., MGMT, DAXX/ATRX/ALT) show promise but require cautious interpretation in routine care. In treatment, radioligand therapy (PRRT) is used earlier in appropriate receptor-positive disease; cabozantinib improves progression-free survival after prior therapy; and belzutifan offers a biomarker-guided option for malignant pheochromocytoma/paraganglioma. Immunotherapy remains limited to defined subsets, including high-grade neoplasms. We appraise strengths and limitations of key trials, note issues of access and toxicity, and highlight active areas in development (SSTR antagonists, alpha emitters, and dose-guided PRRT). Our goal is to provide a concise, evidence-based map of the field to support informed clinical judgment and future research priorities.

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