A Systematic Review and Framework for the Use of Hormone Therapy with Salvage Radiation Therapy for Recurrent Prostate Cancer

Daniel E. Spratt, Robert T. Dess, Zachary S. Zumsteg, Daniel W. Lin, Phuoc T. Tran, Todd M. Morgan, Emmanuel S. Antonarakis, Paul L. Nguyen, Charles J. Ryan, Howard M. Sandler, Matthew R. Cooperberg, Edwin Posadas, Felix Y. Feng

Research output: Research - peer-reviewArticle

Abstract

Context: Salvage radiotherapy (SRT) is a standard of care for men who recur postprostatectomy, and recent randomized trials have assessed the benefit and toxicity of adding hormone therapy (HT) to SRT with differing results. Objective: To perform a systematic review of randomized phase III trials of the use of SRT ± HT and generate a framework for the use of HT with SRT. Evidence acquisition: Systematic literature searches were conducted on February 15, 2017 in three databases (MEDLINE [via PubMed], EMBASE, and ClinicalTrials.gov) for human-only randomized clinical trials from January 30, 1990, through January 30, 2017. Only two randomized trials met all inclusion criteria. Evidence synthesis: Overall survival benefits from HT were found in one trial, which was limited to when follow-up extended to ≥10 yr, pre-SRT prostate-specific antigen (PSA) ≥0.7 ng/ml, or when higher Gleason grade or positive margins were present. Both trials demonstrated a benefit from HT in men with higher pre-SRT PSAs. Three prognostic factors appeared to discriminate improvements in meaningful clinical endpoints (eg, distant metastasis or survival): pre-SRT PSA, Gleason score, and margin status. Two years of bicalutamide monotherapy resulted in higher rates of gynecomastia with a trend for worse survival when given in favorable risk patients, and 6 mo of luteinizing hormone-releasing hormone agonist therapy resulted in higher rates of hot flashes and long-term hypertension. Conclusions: Similar to the selective use of HT with radiotherapy in localized prostate cancer, not all patients appear to derive a meaningful benefit from HT with SRT. Patient, tumor, and treatment factors must be considered when recommending the use of HT with SRT. Knowledge gaps exist in the level 1 data regarding the optimal duration and type of HT, as well as the ability to use predictive biomarkers to personalize the use of HT with SRT. Important clinical trials (RADICALS and NRG GU-006) are aimed to answer these questions. Patient summary: In this report, we performed a systematic review of the literature to determine the benefit and harm of adding hormone therapy to salvage radiotherapy (SRT) for recurrent prostate cancer. We found that the benefit of hormone therapy varied by important prognostic factors, including pre-SRT prostate-specific antigen, Gleason grade, and surgical margin status. Our group then developed a framework on how best to utilize hormone therapy with SRT. The decision to add hormonal therapy to salvage radiation therapy (SRT) should be individualized. Improvements in distant metastasis or survival are most likely in patients with life expectancy of ≥10 yr with a pre-SRT prostate-specific antigen of ≥0.7, Gleason 8-10, and/or positive margins.

LanguageEnglish (US)
JournalEuropean Urology
DOIs
StateAccepted/In press - 2017

Fingerprint

Salvage Therapy
Prostatic Neoplasms
Radiotherapy
Hormones
Therapeutics
Prostate-Specific Antigen
Survival
Neoplasm Metastasis
Hot Flashes
Gynecomastia
Neoplasm Grading
Standard of Care
Life Expectancy
PubMed
Gonadotropin-Releasing Hormone
MEDLINE
Randomized Controlled Trials
Biomarkers
Clinical Trials
Databases

Keywords

  • Hormone therapy
  • Prostate cancer
  • Salvage radiotherapy
  • Systematic review

ASJC Scopus subject areas

  • Urology

Cite this

A Systematic Review and Framework for the Use of Hormone Therapy with Salvage Radiation Therapy for Recurrent Prostate Cancer. / Spratt, Daniel E.; Dess, Robert T.; Zumsteg, Zachary S.; Lin, Daniel W.; Tran, Phuoc T.; Morgan, Todd M.; Antonarakis, Emmanuel S.; Nguyen, Paul L.; Ryan, Charles J.; Sandler, Howard M.; Cooperberg, Matthew R.; Posadas, Edwin; Feng, Felix Y.

In: European Urology, 2017.

Research output: Research - peer-reviewArticle

Spratt, DE, Dess, RT, Zumsteg, ZS, Lin, DW, Tran, PT, Morgan, TM, Antonarakis, ES, Nguyen, PL, Ryan, CJ, Sandler, HM, Cooperberg, MR, Posadas, E & Feng, FY 2017, 'A Systematic Review and Framework for the Use of Hormone Therapy with Salvage Radiation Therapy for Recurrent Prostate Cancer' European Urology. DOI: 10.1016/j.eururo.2017.06.027
Spratt, Daniel E. ; Dess, Robert T. ; Zumsteg, Zachary S. ; Lin, Daniel W. ; Tran, Phuoc T. ; Morgan, Todd M. ; Antonarakis, Emmanuel S. ; Nguyen, Paul L. ; Ryan, Charles J. ; Sandler, Howard M. ; Cooperberg, Matthew R. ; Posadas, Edwin ; Feng, Felix Y./ A Systematic Review and Framework for the Use of Hormone Therapy with Salvage Radiation Therapy for Recurrent Prostate Cancer. In: European Urology. 2017
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abstract = "Context: Salvage radiotherapy (SRT) is a standard of care for men who recur postprostatectomy, and recent randomized trials have assessed the benefit and toxicity of adding hormone therapy (HT) to SRT with differing results. Objective: To perform a systematic review of randomized phase III trials of the use of SRT ± HT and generate a framework for the use of HT with SRT. Evidence acquisition: Systematic literature searches were conducted on February 15, 2017 in three databases (MEDLINE [via PubMed], EMBASE, and ClinicalTrials.gov) for human-only randomized clinical trials from January 30, 1990, through January 30, 2017. Only two randomized trials met all inclusion criteria. Evidence synthesis: Overall survival benefits from HT were found in one trial, which was limited to when follow-up extended to ≥10 yr, pre-SRT prostate-specific antigen (PSA) ≥0.7 ng/ml, or when higher Gleason grade or positive margins were present. Both trials demonstrated a benefit from HT in men with higher pre-SRT PSAs. Three prognostic factors appeared to discriminate improvements in meaningful clinical endpoints (eg, distant metastasis or survival): pre-SRT PSA, Gleason score, and margin status. Two years of bicalutamide monotherapy resulted in higher rates of gynecomastia with a trend for worse survival when given in favorable risk patients, and 6 mo of luteinizing hormone-releasing hormone agonist therapy resulted in higher rates of hot flashes and long-term hypertension. Conclusions: Similar to the selective use of HT with radiotherapy in localized prostate cancer, not all patients appear to derive a meaningful benefit from HT with SRT. Patient, tumor, and treatment factors must be considered when recommending the use of HT with SRT. Knowledge gaps exist in the level 1 data regarding the optimal duration and type of HT, as well as the ability to use predictive biomarkers to personalize the use of HT with SRT. Important clinical trials (RADICALS and NRG GU-006) are aimed to answer these questions. Patient summary: In this report, we performed a systematic review of the literature to determine the benefit and harm of adding hormone therapy to salvage radiotherapy (SRT) for recurrent prostate cancer. We found that the benefit of hormone therapy varied by important prognostic factors, including pre-SRT prostate-specific antigen, Gleason grade, and surgical margin status. Our group then developed a framework on how best to utilize hormone therapy with SRT. The decision to add hormonal therapy to salvage radiation therapy (SRT) should be individualized. Improvements in distant metastasis or survival are most likely in patients with life expectancy of ≥10 yr with a pre-SRT prostate-specific antigen of ≥0.7, Gleason 8-10, and/or positive margins.",
keywords = "Hormone therapy, Prostate cancer, Salvage radiotherapy, Systematic review",
author = "Spratt, {Daniel E.} and Dess, {Robert T.} and Zumsteg, {Zachary S.} and Lin, {Daniel W.} and Tran, {Phuoc T.} and Morgan, {Todd M.} and Antonarakis, {Emmanuel S.} and Nguyen, {Paul L.} and Ryan, {Charles J.} and Sandler, {Howard M.} and Cooperberg, {Matthew R.} and Edwin Posadas and Feng, {Felix Y.}",
year = "2017",
doi = "10.1016/j.eururo.2017.06.027",
journal = "European Urology",
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TY - JOUR

T1 - A Systematic Review and Framework for the Use of Hormone Therapy with Salvage Radiation Therapy for Recurrent Prostate Cancer

AU - Spratt,Daniel E.

AU - Dess,Robert T.

AU - Zumsteg,Zachary S.

AU - Lin,Daniel W.

AU - Tran,Phuoc T.

AU - Morgan,Todd M.

AU - Antonarakis,Emmanuel S.

AU - Nguyen,Paul L.

AU - Ryan,Charles J.

AU - Sandler,Howard M.

AU - Cooperberg,Matthew R.

AU - Posadas,Edwin

AU - Feng,Felix Y.

PY - 2017

Y1 - 2017

N2 - Context: Salvage radiotherapy (SRT) is a standard of care for men who recur postprostatectomy, and recent randomized trials have assessed the benefit and toxicity of adding hormone therapy (HT) to SRT with differing results. Objective: To perform a systematic review of randomized phase III trials of the use of SRT ± HT and generate a framework for the use of HT with SRT. Evidence acquisition: Systematic literature searches were conducted on February 15, 2017 in three databases (MEDLINE [via PubMed], EMBASE, and ClinicalTrials.gov) for human-only randomized clinical trials from January 30, 1990, through January 30, 2017. Only two randomized trials met all inclusion criteria. Evidence synthesis: Overall survival benefits from HT were found in one trial, which was limited to when follow-up extended to ≥10 yr, pre-SRT prostate-specific antigen (PSA) ≥0.7 ng/ml, or when higher Gleason grade or positive margins were present. Both trials demonstrated a benefit from HT in men with higher pre-SRT PSAs. Three prognostic factors appeared to discriminate improvements in meaningful clinical endpoints (eg, distant metastasis or survival): pre-SRT PSA, Gleason score, and margin status. Two years of bicalutamide monotherapy resulted in higher rates of gynecomastia with a trend for worse survival when given in favorable risk patients, and 6 mo of luteinizing hormone-releasing hormone agonist therapy resulted in higher rates of hot flashes and long-term hypertension. Conclusions: Similar to the selective use of HT with radiotherapy in localized prostate cancer, not all patients appear to derive a meaningful benefit from HT with SRT. Patient, tumor, and treatment factors must be considered when recommending the use of HT with SRT. Knowledge gaps exist in the level 1 data regarding the optimal duration and type of HT, as well as the ability to use predictive biomarkers to personalize the use of HT with SRT. Important clinical trials (RADICALS and NRG GU-006) are aimed to answer these questions. Patient summary: In this report, we performed a systematic review of the literature to determine the benefit and harm of adding hormone therapy to salvage radiotherapy (SRT) for recurrent prostate cancer. We found that the benefit of hormone therapy varied by important prognostic factors, including pre-SRT prostate-specific antigen, Gleason grade, and surgical margin status. Our group then developed a framework on how best to utilize hormone therapy with SRT. The decision to add hormonal therapy to salvage radiation therapy (SRT) should be individualized. Improvements in distant metastasis or survival are most likely in patients with life expectancy of ≥10 yr with a pre-SRT prostate-specific antigen of ≥0.7, Gleason 8-10, and/or positive margins.

AB - Context: Salvage radiotherapy (SRT) is a standard of care for men who recur postprostatectomy, and recent randomized trials have assessed the benefit and toxicity of adding hormone therapy (HT) to SRT with differing results. Objective: To perform a systematic review of randomized phase III trials of the use of SRT ± HT and generate a framework for the use of HT with SRT. Evidence acquisition: Systematic literature searches were conducted on February 15, 2017 in three databases (MEDLINE [via PubMed], EMBASE, and ClinicalTrials.gov) for human-only randomized clinical trials from January 30, 1990, through January 30, 2017. Only two randomized trials met all inclusion criteria. Evidence synthesis: Overall survival benefits from HT were found in one trial, which was limited to when follow-up extended to ≥10 yr, pre-SRT prostate-specific antigen (PSA) ≥0.7 ng/ml, or when higher Gleason grade or positive margins were present. Both trials demonstrated a benefit from HT in men with higher pre-SRT PSAs. Three prognostic factors appeared to discriminate improvements in meaningful clinical endpoints (eg, distant metastasis or survival): pre-SRT PSA, Gleason score, and margin status. Two years of bicalutamide monotherapy resulted in higher rates of gynecomastia with a trend for worse survival when given in favorable risk patients, and 6 mo of luteinizing hormone-releasing hormone agonist therapy resulted in higher rates of hot flashes and long-term hypertension. Conclusions: Similar to the selective use of HT with radiotherapy in localized prostate cancer, not all patients appear to derive a meaningful benefit from HT with SRT. Patient, tumor, and treatment factors must be considered when recommending the use of HT with SRT. Knowledge gaps exist in the level 1 data regarding the optimal duration and type of HT, as well as the ability to use predictive biomarkers to personalize the use of HT with SRT. Important clinical trials (RADICALS and NRG GU-006) are aimed to answer these questions. Patient summary: In this report, we performed a systematic review of the literature to determine the benefit and harm of adding hormone therapy to salvage radiotherapy (SRT) for recurrent prostate cancer. We found that the benefit of hormone therapy varied by important prognostic factors, including pre-SRT prostate-specific antigen, Gleason grade, and surgical margin status. Our group then developed a framework on how best to utilize hormone therapy with SRT. The decision to add hormonal therapy to salvage radiation therapy (SRT) should be individualized. Improvements in distant metastasis or survival are most likely in patients with life expectancy of ≥10 yr with a pre-SRT prostate-specific antigen of ≥0.7, Gleason 8-10, and/or positive margins.

KW - Hormone therapy

KW - Prostate cancer

KW - Salvage radiotherapy

KW - Systematic review

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