title: Ablative therapy for people with localised prostate cancer: a systematic review and economic evaluation.
abstract: BACKGROUND
  For people with localised prostate cancer, active treatments are effective but have significant side effects. Minimally invasive treatments that destroy (or ablate) either the entire gland or the part of the prostate with cancer may be as effective and cause less side effects at an acceptable cost. Such therapies include cryotherapy, high-intensity focused ultrasound (HIFU) and brachytherapy, among others.
  
  
  OBJECTIVE
  This study aimed to determine the relative clinical effectiveness and cost-effectiveness of ablative therapies compared with radical prostatectomy (RP), external beam radiotherapy (EBRT) and active surveillance (AS) for primary treatment of localised prostate cancer, and compared with RP for salvage treatment of localised prostate cancer which has recurred after initial treatment with EBRT.
  
  
  METHODS
  MEDLINE (1946 to March week 3, 2013), MEDLINE In-Process & Other Non-Indexed Citations (29 March 2013), EMBASE (1974 to week 13, 2013), Bioscience Information Service (BIOSIS) (1956 to 1 April 2013), Science Citation Index (1970 to 1 April 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (issue 3, 2013), Cochrane Database of Systematic Reviews (CDSR) (issue 3, 2013), Database of Abstracts of Reviews of Effects (DARE) (inception to March 2013) and Health Technology Assessment (HTA) (inception to March 2013) databases were searched. Costs were obtained from NHS sources.
  
  
  METHODS
  Evidence was drawn from randomised controlled trials (RCTs) and non-RCTs, and from case series for the ablative procedures only, in people with localised prostate cancer. For primary therapy, the ablative therapies were cryotherapy, HIFU, brachytherapy and other ablative therapies. The comparators were AS, RP and EBRT. For salvage therapy, the ablative therapies were cryotherapy and HIFU. The comparator was RP. Outcomes were cancer related, adverse effects (functional and procedural) and quality of life. Two reviewers extracted data and carried out quality assessment. Meta-analysis used a Bayesian indirect mixed-treatment comparison. Data were incorporated into an individual simulation Markov model to estimate cost-effectiveness.
  
  
  RESULTS
  The searches identified 121 studies for inclusion in the review of patients undergoing primary treatment and nine studies for the review of salvage treatment. Cryotherapy [3995 patients; 14 case series, 1 RCT and 4 non-randomised comparative studies (NRCSs)], HIFU (4000 patients; 20 case series, 1 NRCS) and brachytherapy (26,129 patients; 2 RCTs, 38 NRCSs) studies provided limited data for meta-analyses. All studies were considered at high risk of bias. There was no robust evidence that mortality (4-year survival 93% for cryotherapy, 99% for HIFU, 91% for EBRT) or other cancer-specific outcomes differed between treatments. For functional and quality-of-life outcomes, the paucity of data prevented any definitive conclusions from being made, although data on incontinence rates and erectile dysfunction for all ablative procedures were generally numerically lower than for non-ablative procedures. The safety profiles were comparable with existing treatments. Studies reporting the use of focal cryotherapy suggested that incontinence rates may be better than for whole-gland treatment. Data on AS, salvage treatment and other ablative therapies were too limited. The cost-effectiveness analysis confirmed the uncertainty from the clinical review and that there is no technology which appears superior, on the basis of current evidence, in terms of average cost-effectiveness. The probabilistic sensitivity analyses suggest that a number of ablative techniques are worthy of further research.
  
  
  CONCLUSIONS
  The main limitations were the quantity and quality of the data available on cancer-related outcomes and dysfunction.
  
  
  CONCLUSIONS
  The findings indicate that there is insufficient evidence to form any clear recommendations on the use of ablative therapies in order to influence current clinical practice. Research efforts in the use of ablative therapies in the management of prostate cancer should now be concentrated on the performance of RCTs and the generation of standardised outcomes.
  
  
  BACKGROUND
  This study is registered as PROSPERO CRD42012002461.
  
  
  BACKGROUND
  The National Institute for Health Research Health Technology Assessment programme.
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Ramsay
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Temitope E
authors.initials: TE
authors.lastname: Adewuyi
authors.affiliation: Faculty of Health & Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Gray
authors.affiliation: Health Economics Group, Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Jenni
authors.initials: J
authors.lastname: Hislop
authors.affiliation: School of Biology, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Mark D F
authors.initials: MD
authors.lastname: Shirley
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Shalmini
authors.initials: S
authors.lastname: Jayakody
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Graeme
authors.initials: G
authors.lastname: MacLennan
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Fraser
authors.affiliation: Academic Urology Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: MacLennan
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Miriam
authors.initials: M
authors.lastname: Brazzelli
authors.affiliation: Academic Urology Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: James
authors.initials: J
authors.lastname: N'Dow
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Pickard
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Robertson
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Kieran
authors.initials: K
authors.lastname: Rothnie
authors.affiliation: School of Biology, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Rushton
authors.affiliation: Health Economics Group, Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Luke
authors.initials: L
authors.lastname: Vale
authors.affiliation: Academic Urology Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Lam
mesh_terms: D055011:Ablation Techniques / Q000009:adverse effects / Q000191:economics / Q000379:methods / Q000706:statistics & numerical data; D000368:Aged; D000369:Aged, 80 and over; D003362:Cost-Benefit Analysis; D016206:Databases, Bibliographic; D007172:Erectile Dysfunction / Q000209:etiology; D006801:Humans; D015994:Incidence; D000069451:Long Term Adverse Effects; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D010043:Outcome and Process Assessment, Health Care / Q000191:economics / Q000706:statistics & numerical data*; D015995:Prevalence; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000191:economics / Q000453:epidemiology / Q000601:surgery*; D019057:Quality-Adjusted Life Years; D013222:State Medicine / Q000191:economics*; D016019:Survival Analysis; D006113:United Kingdom; D014549:Urinary Incontinence / Q000209:etiology
chemical_list: D017430:Prostate-Specific Antigen