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Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations

BACKGROUND: Androgen deprivation therapy (ADT) is foundational in the management of advanced prostate cancer (PCa) and has benefitted from a recent explosion in scientific advances. These include approval of new therapies that suppress testosterone (T) levels or inactivate its function, improvements...

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Autores principales: Crawford, E. David, Heidenreich, Axel, Lawrentschuk, Nathan, Tombal, Bertrand, Pompeo, Antonio C. L., Mendoza-Valdes, Arturo, Miller, Kurt, Debruyne, Frans M. J., Klotz, Laurence
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370592/
https://www.ncbi.nlm.nih.gov/pubmed/30131604
http://dx.doi.org/10.1038/s41391-018-0079-0
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author Crawford, E. David
Heidenreich, Axel
Lawrentschuk, Nathan
Tombal, Bertrand
Pompeo, Antonio C. L.
Mendoza-Valdes, Arturo
Miller, Kurt
Debruyne, Frans M. J.
Klotz, Laurence
author_facet Crawford, E. David
Heidenreich, Axel
Lawrentschuk, Nathan
Tombal, Bertrand
Pompeo, Antonio C. L.
Mendoza-Valdes, Arturo
Miller, Kurt
Debruyne, Frans M. J.
Klotz, Laurence
author_sort Crawford, E. David
collection PubMed
description BACKGROUND: Androgen deprivation therapy (ADT) is foundational in the management of advanced prostate cancer (PCa) and has benefitted from a recent explosion in scientific advances. These include approval of new therapies that suppress testosterone (T) levels or inactivate its function, improvements in diagnostic and assay technologies, identification of lower therapeutic targets for T, discovery of the relevance of germline genetic mutations and identification of the benefits of sequential and combination therapies. METHODS: This review discusses the clinical profiles of the most up-to-date options for ADT, best practices for managing patients with advanced PCa and future directions in therapy. RESULTS AND CONCLUSIONS: Modern assay technologies reveal that bilateral orchiectomy results in a serum T level of approximately 15 ng/dL as compared to the historical definition of castration of T < 50 ng/dL. Evidence shows that lowering T levels to <20 ng/dL improves patient survival and delays disease progression. Routine monitoring of T in addition to prostate-specific antigen throughout treatment is important to ensure continuing efficacy of T suppression. New drugs that inhibit androgen signaling in combination with traditional ADT suppress T activity to near zero and have significantly improved patient survival. When personalizing ADT regimens physicians should consider a number of factors including initiation and duration of ADT, monitoring of T levels and PSA, the possibility of switching monotherapies if a patient does not achieve adequate T suppression, and consideration of intermittent vs. continuous ADT according to patients’ lifestyles, comorbidities, risk factors and tolerance to treatment.
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spelling pubmed-63705922019-02-13 Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations Crawford, E. David Heidenreich, Axel Lawrentschuk, Nathan Tombal, Bertrand Pompeo, Antonio C. L. Mendoza-Valdes, Arturo Miller, Kurt Debruyne, Frans M. J. Klotz, Laurence Prostate Cancer Prostatic Dis Review Article BACKGROUND: Androgen deprivation therapy (ADT) is foundational in the management of advanced prostate cancer (PCa) and has benefitted from a recent explosion in scientific advances. These include approval of new therapies that suppress testosterone (T) levels or inactivate its function, improvements in diagnostic and assay technologies, identification of lower therapeutic targets for T, discovery of the relevance of germline genetic mutations and identification of the benefits of sequential and combination therapies. METHODS: This review discusses the clinical profiles of the most up-to-date options for ADT, best practices for managing patients with advanced PCa and future directions in therapy. RESULTS AND CONCLUSIONS: Modern assay technologies reveal that bilateral orchiectomy results in a serum T level of approximately 15 ng/dL as compared to the historical definition of castration of T < 50 ng/dL. Evidence shows that lowering T levels to <20 ng/dL improves patient survival and delays disease progression. Routine monitoring of T in addition to prostate-specific antigen throughout treatment is important to ensure continuing efficacy of T suppression. New drugs that inhibit androgen signaling in combination with traditional ADT suppress T activity to near zero and have significantly improved patient survival. When personalizing ADT regimens physicians should consider a number of factors including initiation and duration of ADT, monitoring of T levels and PSA, the possibility of switching monotherapies if a patient does not achieve adequate T suppression, and consideration of intermittent vs. continuous ADT according to patients’ lifestyles, comorbidities, risk factors and tolerance to treatment. Nature Publishing Group UK 2018-08-21 2019 /pmc/articles/PMC6370592/ /pubmed/30131604 http://dx.doi.org/10.1038/s41391-018-0079-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Review Article
Crawford, E. David
Heidenreich, Axel
Lawrentschuk, Nathan
Tombal, Bertrand
Pompeo, Antonio C. L.
Mendoza-Valdes, Arturo
Miller, Kurt
Debruyne, Frans M. J.
Klotz, Laurence
Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations
title Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations
title_full Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations
title_fullStr Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations
title_full_unstemmed Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations
title_short Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations
title_sort androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370592/
https://www.ncbi.nlm.nih.gov/pubmed/30131604
http://dx.doi.org/10.1038/s41391-018-0079-0
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