title: Hexyl aminolevulinate-guided fluorescence cystoscopy in the diagnosis and follow-up of patients with non-muscle-invasive bladder cancer: a critical review of the current literature.
abstract: BACKGROUND
  Controversy exists regarding the therapeutic benefit and cost effectiveness of photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) or hexyl aminolevulinate (HAL) in addition to white-light cystoscopy (WLC) in the management of non-muscle-invasive bladder cancer (NMIBC).
  
  
  OBJECTIVE
  To systematically evaluate evidence regarding the therapeutic benefits and economic considerations of PDD in NMIBC detection and treatment.
  
  
  METHODS
  We performed a critical review of PubMed/Medline, Embase, and the Cochrane Library in October 2012 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT) and Standards for the Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forty-four publications were selected for inclusion in this analysis.
  
  
  RESULTS
  Included reports used 5-ALA (in 26 studies), HAL (15 studies), or both (three studies) as photosensitising agents. PDD increased the detection of both papillary tumours (by 7-29%) and flat carcinoma in situ (CIS; by 25-30%) and reduced the rate of residual tumours after transurethral resection of bladder tumour (TURBT; by an average of 20%) compared to WLC alone. Superior recurrence-free survival (RFS) rates and prolonged RFS intervals were reported for PDD, compared to WLC in most studies. PDD did not appear to reduce disease progression. Our findings are limited by tumour heterogeneity and a lack of NMIBC risk stratification in many reports or adjustment for intravesical therapy use in most studies. Although cost effectiveness has been demonstrated for 5-ALA, it has not been studied for HAL.
  
  
  CONCLUSIONS
  Moderately strong evidence exists that PDD improves tumour detection and reduces residual disease after TURBT compared with WLC. This has been shown to improve RFS but not progression to more advanced disease. Further work to evaluate cost effectiveness of PDD is required.
authors.affiliation: Department of Urology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. mrink@uke.de
authors.forename: Michael
authors.initials: M
authors.lastname: Rink
authors.forename: Marko
authors.initials: M
authors.lastname: Babjuk
authors.forename: James W F
authors.initials: JW
authors.lastname: Catto
authors.forename: Patrice
authors.initials: P
authors.lastname: Jichlinski
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Herbert
authors.initials: H
authors.lastname: Stepp
authors.forename: Dirk
authors.initials: D
authors.lastname: Zaak
authors.forename: J Alfred
authors.initials: JA
authors.lastname: Witjes
mesh_terms: D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000191:economics; D003362:Cost-Benefit Analysis; D015653:Cystectomy; D003558:Cystoscopy / Q000191:economics / Q000379:methods*; D018572:Disease-Free Survival; D017048:Health Care Costs; D006801:Humans; D009361:Neoplasm Invasiveness; D018365:Neoplasm, Residual; D017319:Photosensitizing Agents / Q000191:economics; D011237:Predictive Value of Tests; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000473:pathology* / Q000601:surgery; D001749:Urinary Bladder Neoplasms / Q000209:etiology / Q000401:mortality / Q000473:pathology* / Q000601:surgery / Q000628:therapy
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; C419924:5-aminolevulinic acid hexyl ester
keywords: Cost effectiveness; Hexyl aminolevulinate; Non–muscle-invasive bladder cancer; Photodynamic diagnosis; Recurrence-free survival; Tumour detection; Urothelial cancer