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Radiation With or Without Androgen Deprivation Therapy for Localized Prostate Cancer

Radiation With or Without Androgen Deprivation Therapy for Localized Prostate Cancer To the Editor In an update of their randomized clinical trial, Dr D’Amico and colleagues1 reported that combined radiation therapy (RT) and androgen deprivation therapy (ADT) was no longer associated with an overall survival benefit among 206 men with unfavorable localized prostate cancer after a median of 16.6 years. These observations are inconsistent with 2 prior reports of this trial and with the results of multiple randomized trials (involving >8000 men) that have consistently demonstrated a survival benefit with the addition of ADT for men receiving RT with intermediate, high-risk, and locally advanced prostate cancer.2 In addition, D’Amico and colleagues performed an unplanned exploratory analysis of patients with moderate or severe comorbidity and reported that these men had a statistically significantly increased risk of overall and cardiac mortality associated with RT and ADT. Although the authors acknowledged study limitations including low event rates (only 3 prostate cancer deaths and 6 cardiac-related deaths among the 25 men with moderate or severe comorbidity that received RT alone), alternative contributing factors including underpowered end points or a late wave in other causes of death may account for the observations. In contrast to the study by D’Amico and colleagues, a large randomized clinical trial of men with localized prostate cancer demonstrated that the addition of ADT to RT improved overall and disease-specific survival with no significantly increased risk of cardiovascular mortality.3 This study analyzed more than 1900 patients and included more than 400 men deemed at greater risk for cardiovascular mortality based on age and history of cardiovascular disease or diabetes. These data are consistent with a meta-analysis that included more than 4000 men treated with RT with or without ADT and more than 500 cardiac-related deaths that demonstrated no increased risk of cardiovascular mortality associated with ADT.4 Based on the best available and most consistent level 1 evidence, RT and ADT remain the standard of care for patients with intermediate and high-risk prostate cancer. In addition, most available data show that treatment including ADT does not increase cardiovascular mortality risk, including in patients with cardiac risk factors.3,5 Nevertheless, toxicity of therapy and competing causes of mortality should be considered within the context of appropriate prostate cancer management options during informed decision-making discussions with patients. Section Editor: Jody W. Zylke, MD, Deputy Editor. Back to top Article Information Corresponding Author: Jason A. Efstathiou, MD, DPhil, Department of Radiation Oncology, 100 Blossom St, Cox 3, Massachusetts General Hospital, Boston, MA 02114 (jefstathiou@partners.org). Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. References 1. D’Amico AV, Chen M-H, Renshaw A, Loffredo M, Kantoff PW. Long-term follow-up of a randomized trial of radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA. 2015;314(12):1291-1293.PubMedGoogle ScholarCrossref 2. Pagliarulo V, Bracarda S, Eisenberger MA, et al. Contemporary role of androgen deprivation therapy for prostate cancer. Eur Urol. 2012;61(1):11-25.PubMedGoogle ScholarCrossref 3. Voog JC, Paulus R, Shipley WU, et al. Cardiovascular mortality following short-term androgen deprivation in clinically localized prostate cancer: an analysis of RTOG 94-08. Eur Urol. 2016;69(2):204-210. PubMedGoogle ScholarCrossref 4. Nguyen PL, Je Y, Schutz FA, et al. Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. JAMA. 2011;306(21):2359-2366.PubMedGoogle ScholarCrossref 5. Efstathiou JA, Bae K, Shipley WU, et al. Cardiovascular mortality after androgen deprivation therapy for locally advanced prostate cancer: RTOG 85-31. J Clin Oncol. 2009;27(1):92-99.PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Radiation With or Without Androgen Deprivation Therapy for Localized Prostate Cancer

JAMA , Volume 315 (10) – Mar 8, 2016

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Publisher
American Medical Association
Copyright
Copyright © 2016 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.2015.17567
Publisher site
See Article on Publisher Site

Abstract

To the Editor In an update of their randomized clinical trial, Dr D’Amico and colleagues1 reported that combined radiation therapy (RT) and androgen deprivation therapy (ADT) was no longer associated with an overall survival benefit among 206 men with unfavorable localized prostate cancer after a median of 16.6 years. These observations are inconsistent with 2 prior reports of this trial and with the results of multiple randomized trials (involving >8000 men) that have consistently demonstrated a survival benefit with the addition of ADT for men receiving RT with intermediate, high-risk, and locally advanced prostate cancer.2 In addition, D’Amico and colleagues performed an unplanned exploratory analysis of patients with moderate or severe comorbidity and reported that these men had a statistically significantly increased risk of overall and cardiac mortality associated with RT and ADT. Although the authors acknowledged study limitations including low event rates (only 3 prostate cancer deaths and 6 cardiac-related deaths among the 25 men with moderate or severe comorbidity that received RT alone), alternative contributing factors including underpowered end points or a late wave in other causes of death may account for the observations. In contrast to the study by D’Amico and colleagues, a large randomized clinical trial of men with localized prostate cancer demonstrated that the addition of ADT to RT improved overall and disease-specific survival with no significantly increased risk of cardiovascular mortality.3 This study analyzed more than 1900 patients and included more than 400 men deemed at greater risk for cardiovascular mortality based on age and history of cardiovascular disease or diabetes. These data are consistent with a meta-analysis that included more than 4000 men treated with RT with or without ADT and more than 500 cardiac-related deaths that demonstrated no increased risk of cardiovascular mortality associated with ADT.4 Based on the best available and most consistent level 1 evidence, RT and ADT remain the standard of care for patients with intermediate and high-risk prostate cancer. In addition, most available data show that treatment including ADT does not increase cardiovascular mortality risk, including in patients with cardiac risk factors.3,5 Nevertheless, toxicity of therapy and competing causes of mortality should be considered within the context of appropriate prostate cancer management options during informed decision-making discussions with patients. Section Editor: Jody W. Zylke, MD, Deputy Editor. Back to top Article Information Corresponding Author: Jason A. Efstathiou, MD, DPhil, Department of Radiation Oncology, 100 Blossom St, Cox 3, Massachusetts General Hospital, Boston, MA 02114 (jefstathiou@partners.org). Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. References 1. D’Amico AV, Chen M-H, Renshaw A, Loffredo M, Kantoff PW. Long-term follow-up of a randomized trial of radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA. 2015;314(12):1291-1293.PubMedGoogle ScholarCrossref 2. Pagliarulo V, Bracarda S, Eisenberger MA, et al. Contemporary role of androgen deprivation therapy for prostate cancer. Eur Urol. 2012;61(1):11-25.PubMedGoogle ScholarCrossref 3. Voog JC, Paulus R, Shipley WU, et al. Cardiovascular mortality following short-term androgen deprivation in clinically localized prostate cancer: an analysis of RTOG 94-08. Eur Urol. 2016;69(2):204-210. PubMedGoogle ScholarCrossref 4. Nguyen PL, Je Y, Schutz FA, et al. Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. JAMA. 2011;306(21):2359-2366.PubMedGoogle ScholarCrossref 5. Efstathiou JA, Bae K, Shipley WU, et al. Cardiovascular mortality after androgen deprivation therapy for locally advanced prostate cancer: RTOG 85-31. J Clin Oncol. 2009;27(1):92-99.PubMedGoogle ScholarCrossref

Journal

JAMAAmerican Medical Association

Published: Mar 8, 2016

References