Reappraisal of Neuroendocrine Tumor Classification of the Prostate Gland: Translating Molecular Insights into Clinical Practice.

Neuroendocrine tumors (NETs) of the prostate gland represent a distinct entity within the spectrum of prostate cancer, characterized by neuroendocrine differentiation on morphology and unique clinical behavior. Despite their clinical significance, there remains a lack of consensus regarding their diagnosis, classification, immunohistochemical evaluation, and management. A comprehensive understanding of the molecular and clinical heterogeneity of prostate NETs is essential for developing tailored treatment strategies and improving patient outcomes. Over the years, there has been a continuous effort to refine the terminology and classification of neuroendocrine tumors of the prostate. The current WHO 2022 classification scheme for genitourinary neuroendocrine neoplasms provides a standardized framework. However, given the substantial clinical and molecular heterogeneity of prostate NETs, there is an emerging need for an organ-specific classification system that better captures the biological and clinical diversity of these tumors. In this review, we propose a novel classification system for neuroendocrine neoplasms (NENs) of the prostate that integrates both histomorphology and clinical context. With the growing role of liquid biopsy and molecular biomarkers, there is a shift towards more precise, real-time detection of disease progression and treatment resistance. This review highlights the importance of a more nuanced, biologically and clinically informed approach to the diagnosis and management of prostate NETs. A dedicated classification system, combined with advancements in precision genomics and targeted therapies, holds significant promise for improving outcomes in patients with these rare and challenging tumors.