title: Intermittent vs Continuous Androgen Deprivation Therapy for Prostate Cancer: A Systematic Review and Meta-analysis.
abstract: OBJECTIVE
  Androgen deprivation is the standard therapy for patients with advanced or recurrent prostate cancer. However, this treatment causes adverse effects, alters quality of life, and may lead to castration-resistant disease. Intermittent androgen deprivation has been studied as an alternative.
  
  
  OBJECTIVE
  To conduct a systematic review and meta-analysis comparing the efficacy and tolerability of intermittent vs continuous androgen deprivation therapy in patients with prostate cancer.
  
  
  METHODS
  We searched Cochrane CENTRAL, Medline, Embase, Web of Science, Biosis, National Technical Information Service, OpenSIGLE, and Google Scholar from inception of each database through March 2014. References from published guidelines, reviews, and other relevant articles were also considered.
  
  
  METHODS
  We selected randomized clinical trials comparing intermittent vs continuous androgen deprivation therapy in patients with prostate cancer.
  
  
  METHODS
  Two reviewers performed study selection, data abstraction, and risk of bias assessment. We calculated hazard ratios (HRs) with the inverse variance method and risk ratios with the Mantel-Haenszel method, using random effect models. A noninferiority analysis was conducted for overall survival with a margin of 1.15 for the upper boundary of the HR. We assessed heterogeneity using the I2 index.
  
  
  METHODS
  Primary outcomes were overall survival and quality of life. Secondary outcomes were cancer-specific survival, progression-free survival, time to castration resistance, skeletal-related events, and adverse effects.
  
  
  RESULTS
  From 10 510 references, we included 22 articles from 15 trials (6856 patients) published between 2000 and 2013. All but 1 study had an unclear or high risk of bias. We observed no significant difference between intermittent and continuous therapy for overall survival (HR, 1.02; 95% CI, 0.93-1.11; 8 trials, 5352 patients), cancer-specific survival (HR, 1.02; 95% CI, 0.87-1.19; 5 trials, 3613 patients), and progression-free survival (HR, 0.94; 95% CI, 0.84-1.05; 4 trials, 1774 patients). There was minimal difference in patients' self-reported quality of life between the 2 interventions. Most trials observed an improvement in physical and sexual functioning with intermittent therapy.
  
  
  CONCLUSIONS
  Intermittent androgen deprivation was not inferior to continuous therapy with respect to the overall survival. Some quality-of-life criteria seemed improved with intermittent therapy. Intermittent androgen deprivation can be considered as an alternative option in patients with recurrent or metastatic prostate cancer.
authors.affiliation: Division of Radiation Oncology, Department of Medicine, CHU de Québec, Université Laval, Québec City, Québec, Canada.
authors.forename: Sindy
authors.initials: S
authors.lastname: Magnan
authors.affiliation: Department of Internal Medicine, Sections of Hematology/Medical Oncology and Critical Care, University of Manitoba, Winnipeg, Manitoba, Canada3Department of Haematology and Medical Oncology, Cancercare Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Ryan
authors.initials: R
authors.lastname: Zarychanski
authors.affiliation: Division of Radiation Oncology, Department of Medicine, CHU de Québec, Université Laval, Québec City, Québec, Canada.
authors.forename: Laurie
authors.initials: L
authors.lastname: Pilote
authors.affiliation: Division of Radiation Oncology, Department of Medicine, CHU de Québec, Université Laval, Québec City, Québec, Canada.
authors.forename: Laurence
authors.initials: L
authors.lastname: Bernier
authors.affiliation: CHU de Québec Research Center, Université Laval, Québec City, Québec, Canada.
authors.forename: Michèle
authors.initials: M
authors.lastname: Shemilt
authors.affiliation: Division of Radiation Oncology, Department of Medicine, CHU de Québec, Université Laval, Québec City, Québec, Canada4CHU de Québec Research Center, Université Laval, Québec City, Québec, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Vigneault
authors.affiliation: CHU de Québec Research Center, Université Laval, Québec City, Québec, Canada5Division of Urology, Department of Surgery, CHU de Québec, Université Laval, Québec City, Québec, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Fradet
authors.affiliation: CHU de Québec Research Center, Université Laval, Québec City, Québec, Canada6Division of Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, CHU de Québec, Université Laval, Québec City, Québec, Canada.
authors.forename: Alexis F
authors.initials: AF
authors.lastname: Turgeon
mesh_terms: D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal