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Review
. 2024 Apr;84(5):426-440.
doi: 10.1002/pros.24664. Epub 2024 Jan 3.

Diagnosis and management of neuroendocrine prostate cancer

Ivan de Kouchkovsky  1   2 , Emily Chan  1   3 , Charles Schloss  4 , Christian Poehlein  4 , Rahul Aggarwal  1   2
Affiliations
Review

Diagnosis and management of neuroendocrine prostate cancer

Ivan de Kouchkovsky et al. Prostate. 2024 Apr.

Abstract

Background: Although most patients with prostate cancer (PC) respond to initial androgen deprivation therapy (ADT), castration-resistant disease invariably develops. Progression to treatment-emergent neuroendocrine PC (t-NEPC) represents a unique mechanism of resistance to androgen receptor (AR)-targeted therapy in which lineage plasticity and neuroendocrine differentiation induce a phenotypic switch from an AR-driven adenocarcinoma to an AR-independent NEPC. t-NEPC is characterized by an aggressive clinical course, increased resistance to AR-targeted therapies, and a poor overall prognosis.

Methods: This review provides an overview of our current knowledge of NEPC, with a focus on the unmet needs, diagnosis, and clinical management of t-NEPC.

Results: Evidence extrapolated from the literature on small cell lung cancer or data from metastatic castration-resistant PC (mCRPC) cohorts enriched for t-NEPC suggests an increased sensitivity to platinum-based chemotherapy. However, optimal strategies for managing t-NEPC have not been established, and prospective clinical trial data are limited. Intertumoral heterogeneity within a given patient, as well as the lack of robust molecular or clinical biomarkers for early detection, often lead to delays in diagnosis and prolonged treatment with suboptimal strategies (i.e., conventional chemohormonal therapies for mCRPC), which may further contribute to poor outcomes.

Conclusions: Recent advances in genomic and molecular classification of NEPC and the development of novel biomarkers may facilitate an early diagnosis, help to identify promising therapeutic targets, and improve the selection of patients most likely to benefit from NEPC-targeted therapies.

Keywords: disease management; molecular targeted therapy; neuroendocrine tumors; prostate cancer.

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REFERENCES

    1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
    1. Vellky JE, Ricke WA. Development and prevalence of castration-resistant prostate cancer subtypes. Neoplasia. 2020;22(11):566-575. doi:10.1016/j.neo.2020.09.002
    1. Crowley F, Sterpi M, Buckley C, Margetich L, Handa S, Dovey Z. A review of the pathophysiological mechanisms underlying castration-resistant prostate cancer. Res Rep Urol. 2021;13:457-472. doi:10.2147/rru.S264722
    1. Chandrasekar T, Yang JC, Gao AC, Evans CP. Mechanisms of resistance in castration-resistant prostate cancer (CRPC). Transl Androl Urol. 2015;4(3):365-380. doi:10.3978/j.issn.2223-4683.2015.05.02
    1. Nakazawa M, Paller C, Kyprianou N. Mechanisms of therapeutic resistance in prostate cancer. Curr Oncol Rep. 2017;19(2):13. doi:10.1007/s11912-017-0568-7

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