title: A systematic review of randomised controlled trials of radiotherapy for localised prostate cancer.
abstract: BACKGROUND
  Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males. A systematic review of randomised controlled trials (RCTs) of radiotherapy and other non-pharmacological management options for localised prostate cancer was undertaken.
  
  
  METHODS
  A search of thirteen databases was carried out until March 2014. RCTs comparing radiotherapy (brachytherapy (BT) or external beam radiotherapy (EBRT)) to other management options i.e. radical prostatectomy (RP), active surveillance, watchful waiting, high intensity focused ultrasound (HIFU), or cryotherapy; each alone or in combination, e.g. with adjuvant hormone therapy (HT), were included. Methods followed guidance by the Centre for Reviews and Dissemination and the Cochrane Collaboration. Indirect comparisons were calculated using the Bucher method.
  
  
  RESULTS
  Thirty-six randomised controlled trials (RCTs, 134 references) were included. EBRT, BT and RP were found to be effective in the management of localised prostate cancer. While higher doses of EBRT seem to be related to favourable survival-related outcomes they might, depending on technique, involve more adverse events, e.g. gastrointestinal and genitourinary toxicity. Combining EBRT with hormone therapy shows a statistically significant advantage regarding overall survival when compared to EBRT alone (Relative risk 1.21, 95% confidence interval 1.12-1.30). Aside from mixed findings regarding urinary function, BT and radical prostatectomy were comparable in terms of quality of life and biochemical progression-free survival while favouring BT regarding patient satisfaction and sexual function. There might be advantages of EBRT (with/without HT) compared to cryoablation (with/without HT). No studies on HIFU were identified.
  
  
  CONCLUSIONS
  Based on this systematic review, there is no strong evidence to support one therapy over another as EBRT, BT and RP can all be considered as effective monotherapies for localised disease with EBRT also effective for post-operative management. All treatments have unique adverse events profiles. Further large, robust RCTs which report treatment-specific and treatment combination-specific outcomes in defined prostate cancer risk groups following established reporting standards are needed. These will strengthen the evidence base for newer technologies, help reinforce current consensus guidelines and establish greater standardisation across practices.
authors.affiliation: Kleijnen Systematic Reviews Ltd, York, UK. Electronic address: robert@systematic-reviews.com.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Wolff
authors.affiliation: Kleijnen Systematic Reviews Ltd, York, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Ryder
authors.affiliation: Department of Radiation Oncology, Gustave Roussy Institute, Villejuif, France.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bossi
authors.affiliation: Department of Urology, Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.affiliation: University of British Columbia, Kelowna, Canada.
authors.forename: Juanita
authors.initials: J
authors.lastname: Crook
authors.affiliation: St. James's Hospital, Leeds, UK.
authors.forename: Ann
authors.initials: A
authors.lastname: Henry
authors.affiliation: Mayo Clinic, Rochester, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Karnes
authors.affiliation: North Shore-LIJ Health System, Great Neck, NY, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Potters
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: de Reijke
authors.affiliation: Mount Sinai, New York, USA.
authors.forename: Nelson
authors.initials: N
authors.lastname: Stone
authors.affiliation: Institute of Health and Nursing Sciences, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Burckhardt
authors.affiliation: Kleijnen Systematic Reviews Ltd, York, UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Duffy
authors.affiliation: Kleijnen Systematic Reviews Ltd, York, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Worthy
authors.affiliation: Kleijnen Systematic Reviews Ltd, York, UK; Care and Public Health Research Institute (CAPHRI), Maastricht University, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Kleijnen
mesh_terms: D018931:Antineoplastic Agents, Hormonal; D001918:Brachytherapy / Q000009:adverse effects / Q000401:mortality; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D003452:Cryosurgery; D018450:Disease Progression; D018572:Disease-Free Survival; D057086:High-Intensity Focused Ultrasound Ablation; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D057832:Watchful Waiting
chemical_list: D018931:Antineoplastic Agents, Hormonal
keywords: Brachytherapy; Cryotherapy; High-intensity focused ultrasound ablation; Prostatectomy; Prostatic neoplasms; Radiotherapy; Review; Watchful waiting