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

doi:10.1016/j.eururo.2017.06.027

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

Eur Urol. 2018 Feb;73(2):156-165. doi: 10.1016/j.eururo.2017.06.027. Epub 2017 Jul 14.

Authors

Affiliations

¹ Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA. Electronic address: sprattda@med.umich.edu.
² Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
³ Department of Radiation Oncology, Cedars Sinai, Los Angeles, CA, USA.
⁴ Department of Urology, University of Washington, Seattle, WA, USA.
⁵ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Department of Urology, University of Michigan, Ann Arbor, MI, USA.
⁷ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁹ Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
¹⁰ Departments of Urology and Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA, USA.
¹¹ Department of Medicine, Cedars Sinai, Los Angeles, CA, USA.
¹² Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.

PMID: 28716370
DOI: 10.1016/j.eururo.2017.06.027

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.

Keywords: Hormone therapy; Prostate cancer; Salvage radiotherapy; Systematic review.

Publication types

Systematic Review

MeSH terms

Antineoplastic Agents, Hormonal / therapeutic use*
Clinical Trials, Phase III as Topic
Combined Modality Therapy
Humans
Male
Neoplasm Recurrence, Local / drug therapy*
Neoplasm Recurrence, Local / radiotherapy*
Prostatic Neoplasms / drug therapy*
Prostatic Neoplasms / radiotherapy*
Randomized Controlled Trials as Topic
Salvage Therapy*

Substances

Antineoplastic Agents, Hormonal