Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial

Liselotte M. S. Boevé, Maarten C. C. M. Hulshof, André N. Vis, Aeilko H. Zwinderman, Jos W. R. Twisk, Wim P. J. Witjes, Karl P. J. Delaere, R. Jeroen A. van Moorselaar, Paul C. M. S. Verhagen, George van Andel

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: The cornerstone of standard treatment for patients with primary bone metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT). Retrospective studies suggest a survival benefit for treatment of the primary prostatic tumour in mPCa, but to date, no randomised-controlled-trials (RCTs) have been published addressing this issue. Objective: To determine whether overall survival is prolonged by adding local treatment of the primary prostatic tumour with external beam radiation therapy (EBRT) to ADT. Design, setting, and participants: The HORRAD trial is a multicentre RCT recruiting 432 patients with prostate-specific antigen (PSA) >20 ng/ml and primary bone mPCa on bone scan between 2004 and 2014. Intervention: Patients were randomised to either ADT with EBRT (radiotherapy group) or ADT alone (control group). Outcome measurements and statistical analysis: Primary endpoint was overall survival. Secondary endpoint was time to PSA progression. Crude and adjusted analyses were applied to evaluate treatment effect. Results and limitations: Median PSA level was 142 ng/ml and 67% of patients had more than five osseous metastases. Median follow up was 47 mo. Median overall survival was 45 mo (95% confidence interval [CI], 40.4–49.6) in the radiotherapy group and 43 mo (95% CI: 32.6–53.4) in the control group (p = 0.4). No significant difference was found in overall survival (hazard ratio [HR]: 0.90; 95% CI: 0.70–1.14; p = 0.4). Median time to PSA progression in the radiotherapy group was 15 mo (95% CI: 11.8–18.2), compared with 12 mo (95% CI: 10.6–13.4) in the control group. The crude HR (0.78; 95% CI: 0.63–0.97) was statistically significant (p = 0.02). Conclusions: The current RCT comparing ADT to ADT with EBRT to the prostate in patients with primary bone mPCa did not show a significant difference in overall survival, although the CI cannot exclude a substantial survival benefit. Further research is needed to confirm our findings. Patient summary: This study investigated the effect of adding radiation therapy to the prostate to hormonal therapy in prostate cancer patients with metastasis to the bone at diagnosis. In our patient group, additional radiotherapy did not improve overall survival. Further research is needed to confirm our findings. Twitter summary: Adding radiotherapy to the prostate in patients with bone metastatic prostate cancer does not improve overall survival. In the current randomised controlled trial, there is no improvement in overall survival when comparing androgen deprivation therapy alone to androgen deprivation therapy with concurrent radiotherapy to the prostate in patients with primary bone metastatic prostate cancer.
Original languageEnglish
Pages (from-to)410-418
Number of pages9
JournalEuropean Urology
Volume75
Issue number3
Early online date2018
DOIs
Publication statusPublished - 1 Mar 2018

Cite this

@article{0f5c3d634c9f40069615d8a076e0afd1,
title = "Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial",
abstract = "Background: The cornerstone of standard treatment for patients with primary bone metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT). Retrospective studies suggest a survival benefit for treatment of the primary prostatic tumour in mPCa, but to date, no randomised-controlled-trials (RCTs) have been published addressing this issue. Objective: To determine whether overall survival is prolonged by adding local treatment of the primary prostatic tumour with external beam radiation therapy (EBRT) to ADT. Design, setting, and participants: The HORRAD trial is a multicentre RCT recruiting 432 patients with prostate-specific antigen (PSA) >20 ng/ml and primary bone mPCa on bone scan between 2004 and 2014. Intervention: Patients were randomised to either ADT with EBRT (radiotherapy group) or ADT alone (control group). Outcome measurements and statistical analysis: Primary endpoint was overall survival. Secondary endpoint was time to PSA progression. Crude and adjusted analyses were applied to evaluate treatment effect. Results and limitations: Median PSA level was 142 ng/ml and 67{\%} of patients had more than five osseous metastases. Median follow up was 47 mo. Median overall survival was 45 mo (95{\%} confidence interval [CI], 40.4–49.6) in the radiotherapy group and 43 mo (95{\%} CI: 32.6–53.4) in the control group (p = 0.4). No significant difference was found in overall survival (hazard ratio [HR]: 0.90; 95{\%} CI: 0.70–1.14; p = 0.4). Median time to PSA progression in the radiotherapy group was 15 mo (95{\%} CI: 11.8–18.2), compared with 12 mo (95{\%} CI: 10.6–13.4) in the control group. The crude HR (0.78; 95{\%} CI: 0.63–0.97) was statistically significant (p = 0.02). Conclusions: The current RCT comparing ADT to ADT with EBRT to the prostate in patients with primary bone mPCa did not show a significant difference in overall survival, although the CI cannot exclude a substantial survival benefit. Further research is needed to confirm our findings. Patient summary: This study investigated the effect of adding radiation therapy to the prostate to hormonal therapy in prostate cancer patients with metastasis to the bone at diagnosis. In our patient group, additional radiotherapy did not improve overall survival. Further research is needed to confirm our findings. Twitter summary: Adding radiotherapy to the prostate in patients with bone metastatic prostate cancer does not improve overall survival. In the current randomised controlled trial, there is no improvement in overall survival when comparing androgen deprivation therapy alone to androgen deprivation therapy with concurrent radiotherapy to the prostate in patients with primary bone metastatic prostate cancer.",
keywords = "Androgen deprivation therapy, Local radiotherapy, Metastatic prostate cancer",
author = "Boev{\'e}, {Liselotte M. S.} and Hulshof, {Maarten C. C. M.} and Vis, {Andr{\'e} N.} and Zwinderman, {Aeilko H.} and Twisk, {Jos W. R.} and Witjes, {Wim P. J.} and Delaere, {Karl P. J.} and Moorselaar, {R. Jeroen A. van} and Verhagen, {Paul C. M. S.} and {van Andel}, George",
note = "Copyright {\circledC} 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.",
year = "2018",
month = "3",
day = "1",
doi = "10.1016/j.eururo.2018.09.008",
language = "English",
volume = "75",
pages = "410--418",
journal = "European Urology",
issn = "0302-2838",
publisher = "Elsevier",
number = "3",

}

Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial : Data from the HORRAD Trial. / Boevé, Liselotte M. S.; Hulshof, Maarten C. C. M.; Vis, André N.; Zwinderman, Aeilko H.; Twisk, Jos W. R.; Witjes, Wim P. J.; Delaere, Karl P. J.; Moorselaar, R. Jeroen A. van; Verhagen, Paul C. M. S.; van Andel, George.

In: European Urology, Vol. 75, No. 3, 01.03.2018, p. 410-418.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial

T2 - Data from the HORRAD Trial

AU - Boevé, Liselotte M. S.

AU - Hulshof, Maarten C. C. M.

AU - Vis, André N.

AU - Zwinderman, Aeilko H.

AU - Twisk, Jos W. R.

AU - Witjes, Wim P. J.

AU - Delaere, Karl P. J.

AU - Moorselaar, R. Jeroen A. van

AU - Verhagen, Paul C. M. S.

AU - van Andel, George

N1 - Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Background: The cornerstone of standard treatment for patients with primary bone metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT). Retrospective studies suggest a survival benefit for treatment of the primary prostatic tumour in mPCa, but to date, no randomised-controlled-trials (RCTs) have been published addressing this issue. Objective: To determine whether overall survival is prolonged by adding local treatment of the primary prostatic tumour with external beam radiation therapy (EBRT) to ADT. Design, setting, and participants: The HORRAD trial is a multicentre RCT recruiting 432 patients with prostate-specific antigen (PSA) >20 ng/ml and primary bone mPCa on bone scan between 2004 and 2014. Intervention: Patients were randomised to either ADT with EBRT (radiotherapy group) or ADT alone (control group). Outcome measurements and statistical analysis: Primary endpoint was overall survival. Secondary endpoint was time to PSA progression. Crude and adjusted analyses were applied to evaluate treatment effect. Results and limitations: Median PSA level was 142 ng/ml and 67% of patients had more than five osseous metastases. Median follow up was 47 mo. Median overall survival was 45 mo (95% confidence interval [CI], 40.4–49.6) in the radiotherapy group and 43 mo (95% CI: 32.6–53.4) in the control group (p = 0.4). No significant difference was found in overall survival (hazard ratio [HR]: 0.90; 95% CI: 0.70–1.14; p = 0.4). Median time to PSA progression in the radiotherapy group was 15 mo (95% CI: 11.8–18.2), compared with 12 mo (95% CI: 10.6–13.4) in the control group. The crude HR (0.78; 95% CI: 0.63–0.97) was statistically significant (p = 0.02). Conclusions: The current RCT comparing ADT to ADT with EBRT to the prostate in patients with primary bone mPCa did not show a significant difference in overall survival, although the CI cannot exclude a substantial survival benefit. Further research is needed to confirm our findings. Patient summary: This study investigated the effect of adding radiation therapy to the prostate to hormonal therapy in prostate cancer patients with metastasis to the bone at diagnosis. In our patient group, additional radiotherapy did not improve overall survival. Further research is needed to confirm our findings. Twitter summary: Adding radiotherapy to the prostate in patients with bone metastatic prostate cancer does not improve overall survival. In the current randomised controlled trial, there is no improvement in overall survival when comparing androgen deprivation therapy alone to androgen deprivation therapy with concurrent radiotherapy to the prostate in patients with primary bone metastatic prostate cancer.

AB - Background: The cornerstone of standard treatment for patients with primary bone metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT). Retrospective studies suggest a survival benefit for treatment of the primary prostatic tumour in mPCa, but to date, no randomised-controlled-trials (RCTs) have been published addressing this issue. Objective: To determine whether overall survival is prolonged by adding local treatment of the primary prostatic tumour with external beam radiation therapy (EBRT) to ADT. Design, setting, and participants: The HORRAD trial is a multicentre RCT recruiting 432 patients with prostate-specific antigen (PSA) >20 ng/ml and primary bone mPCa on bone scan between 2004 and 2014. Intervention: Patients were randomised to either ADT with EBRT (radiotherapy group) or ADT alone (control group). Outcome measurements and statistical analysis: Primary endpoint was overall survival. Secondary endpoint was time to PSA progression. Crude and adjusted analyses were applied to evaluate treatment effect. Results and limitations: Median PSA level was 142 ng/ml and 67% of patients had more than five osseous metastases. Median follow up was 47 mo. Median overall survival was 45 mo (95% confidence interval [CI], 40.4–49.6) in the radiotherapy group and 43 mo (95% CI: 32.6–53.4) in the control group (p = 0.4). No significant difference was found in overall survival (hazard ratio [HR]: 0.90; 95% CI: 0.70–1.14; p = 0.4). Median time to PSA progression in the radiotherapy group was 15 mo (95% CI: 11.8–18.2), compared with 12 mo (95% CI: 10.6–13.4) in the control group. The crude HR (0.78; 95% CI: 0.63–0.97) was statistically significant (p = 0.02). Conclusions: The current RCT comparing ADT to ADT with EBRT to the prostate in patients with primary bone mPCa did not show a significant difference in overall survival, although the CI cannot exclude a substantial survival benefit. Further research is needed to confirm our findings. Patient summary: This study investigated the effect of adding radiation therapy to the prostate to hormonal therapy in prostate cancer patients with metastasis to the bone at diagnosis. In our patient group, additional radiotherapy did not improve overall survival. Further research is needed to confirm our findings. Twitter summary: Adding radiotherapy to the prostate in patients with bone metastatic prostate cancer does not improve overall survival. In the current randomised controlled trial, there is no improvement in overall survival when comparing androgen deprivation therapy alone to androgen deprivation therapy with concurrent radiotherapy to the prostate in patients with primary bone metastatic prostate cancer.

KW - Androgen deprivation therapy

KW - Local radiotherapy

KW - Metastatic prostate cancer

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UR - https://www.ncbi.nlm.nih.gov/pubmed/30266309

U2 - 10.1016/j.eururo.2018.09.008

DO - 10.1016/j.eururo.2018.09.008

M3 - Article

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SP - 410

EP - 418

JO - European Urology

JF - European Urology

SN - 0302-2838

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