title: American Brachytherapy Society Task Group Report: Use of androgen deprivation therapy with prostate brachytherapy-A systematic literature review.
abstract: OBJECTIVE
  Prostate brachytherapy (PB) has well-documented excellent long-term outcomes in all risk groups. There are significant uncertainties regarding the role of androgen deprivation therapy (ADT) with brachytherapy. The purpose of this report was to review systemically the published literature and summarize present knowledge regarding the impact of ADT on biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS).
  
  
  METHODS
  A literature search was conducted in Medline and Embase covering the years 1996-2016. Selected were articles with >100 patients, minimum followup 3 years, defined risk stratification, and directly examining the role and impact of ADT on bPFS, CSS, and OS. The studies were grouped to reflect disease risk stratification. We also reviewed the impact of ADT on OS, cardiovascular morbidity, mortality, and on-going brachytherapy randomized controlled trials (RCTs).
  
  
  RESULTS
  Fifty-two selected studies (43,303 patients) were included in this review; 7 high-dose rate and 45 low-dose rate; 25 studies were multi-institutional and 27 single institution (retrospective review or prospective data collection) and 2 were RCTs. The studies were heterogeneous in patient population, risk categories, risk factors, followup time, and treatment administered, including ADT administration and duration (median, 3-12 months);71% of the studies reported a lack of benefit, whereas 28% showed improvement in bPFS with addition of ADT to PB. The lack of benefit was seen in low-risk and favorable intermediate-risk (IR) disease and most high-dose rate studies. A bPFS benefit of up to 15% was seen with ADT use in patients with suboptimal dosimetry, those with multiple adverse risk factors (unfavorable IR [uIR]), and most high-risk (HR) studies. Four studies reported very small benefit to CSS (2%). None of the studies showed OS advantage; however, three studies reported an absolute 5-20% OS detriment with ADT. Literature suggests that OS detriment is more likely in older patients or those with pre-existing cardiovascular disease. Four RCTs with an adequate number of patients and well-defined risk stratification are in progress. One RCT will answer the question regarding the role of ADT with PB in favorable IR patients and the other three RCTs will focus on optimal duration of ADT in the uIR and favorable HR population.
  
  
  CONCLUSIONS
  Patients treated with brachytherapy have excellent long-term disease outcomes. Existing evidence shows no benefit of adding ADT to PB in low-risk and favorable IR patients. UIR and HR patients and those with suboptimal dosimetry may have up to 15% improvement in bPFS with addition of 3-12 months of ADT, with uncertain impact on CSS and a potential detriment on OS. To minimize morbidity, one should exercise caution in prescribing ADT together with PB, in particular to older men and those with existing cardiovascular disease. Due to the retrospective nature of this evidence, significant selection, and treatment bias, no definitive conclusions are possible. RCT is urgently needed to define the potential role and optimal duration of ADT in uIR and favorable HR disease.
authors.affiliation: Department of Radiation Oncology, British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada. Electronic address: mkeyes@bccancer.bc.ca.
authors.forename: M
authors.initials: M
authors.lastname: Keyes
authors.affiliation: Department of Radiation Oncology, Schiffler Cancer Center, Wheeling Jesuit University, Wheeling, WV.
authors.forename: G
authors.initials: G
authors.lastname: Merrick
authors.affiliation: Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: S J
authors.initials: SJ
authors.lastname: Frank
authors.affiliation: Prostate Cancer Center of Seattle, Seattle, WA.
authors.forename: P
authors.initials: P
authors.lastname: Grimm
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: M J
authors.initials: MJ
authors.lastname: Zelefsky
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D001918:Brachytherapy / Q000379:methods*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000628:therapy*; D011879:Radiotherapy Dosage; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen
keywords: Androgen deprivation therapy; Brachytherapy; CSS; OS; Outcomes; Prostate cancer; bPFS