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Second generation anti-androgens and androgen deprivation therapy with radiation therapy in the definitive management of high-risk prostate cancer

Prostate Cancer and Prostatic Diseases volume 26, pages 30–40 (2023)Cite this article

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Abstract

Background

Evolving data suggest that men with high-risk localized prostate cancer may benefit from more potent androgen receptor inhibition in the context of curative intent radiotherapy. Recently updated American Society for Clinical Oncology (ASCO) evidence-based guidelines and the National Comprehensive Cancer Network (NCCN) Guidelines have updated recommendations for the consideration of adding second generation anti-androgens to androgen deprivation therapy (ADT) in men receiving radiation therapy (RT) for noncastrate locally advanced high and very high risk nonmetastatic or node positive prostate cancer.

Methods and results

We conducted a comprehensive review of existing published and abstract presented evidence behind RT with ADT for the definitive management of high-risk prostate cancer, particularly focused on the current phase II and III trial evidence for the addition of second generation anti-androgens to ADT in definitive RT treatment of high-risk prostate cancer and specifically focused on the recent STAMPEDE trial results with abiraterone acetate. We review the biological mechanisms in which second generation anti-androgens may help mitigate ADT resistance and provide radiosensitization through inhibition of DNA repair. Finally, we discuss ongoing clinical trials of potent androgen receptor (AR) inhibitors with ADT in this non-metastatic high-risk radiotherapy setting that may inform on future treatment guidelines.

Conclusions

Recent data suggest an overall survival benefit as well as increased probabilities of disease free and metastasis free survival in men with high and very high-risk localized, node positive, and oligometastatic hormone sensitive prostate cancer with abiraterone acetate and prednisone and support the use of potent AR inhibitors in this setting after informed decision making.

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Fig. 1: Mechanisms of action of second generation androgen receptor (AR) inhibitors.
Fig. 2: DNA is the principal target for the biologic effects of radiation therapy.
Fig. 3: Activation of androgen receptors (AR) can lead to increased DNA repair and radioresistance in prostate cancer.

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Data availability

The authors confirm that the data supporting the findings of this study are available within the article.

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Funding

AJA declares the following relationships: paid consultant with Pfizer, Astellas, Janssen, Bayer, Astrazeneca, Epic Sciences, Exelixis, Myovant, NCCN, BMS, Forma and Merck and receives research funding (to his institution) from Amgen, Forma, Celgene, Pfizer, Astellas, Janssen, Bayer, Dendreon, Novartis, Genentech/Roche, Merck, BMS, Astrazeneca, Constellation, Beigene. Steering committee for Astellas/Pfizer, Astrazeneca, BMS, Merck, Myovant. Dr. Armstrong was supported by NCI 5R01CA233585-04.

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Authors and Affiliations

  1. Department of Radiation Medicine, MedStar Georgetown University Hospital, Washington, DC, USA

    Edina C. Wang

  2. Department of Radiation Oncology, Duke University, Durham, NC, USA

    W. Robert Lee

  3. Division of Medical Oncology, Department of Medicine, Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA

    Andrew J. Armstrong

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Wang, E.C., Lee, W.R. & Armstrong, A.J. Second generation anti-androgens and androgen deprivation therapy with radiation therapy in the definitive management of high-risk prostate cancer. Prostate Cancer Prostatic Dis 26, 30–40 (2023). https://doi.org/10.1038/s41391-022-00598-3

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