title: Photodynamic diagnosis in non-muscle-invasive bladder cancer: a systematic review and cumulative analysis of prospective studies.
abstract: BACKGROUND
  The clinical benefit of photodynamic diagnosis (PDD) with 5-aminolevulinic acid or hexaminolevulinate in addition to white-light cystoscopy (WLC) in bladder cancer has been discussed controversially.
  
  
  OBJECTIVE
  To assess in a systematic review the effect of PDD in addition to WLC on (1) the diagnosis and (2) the therapeutic outcome of primary or recurrent non-muscle-invasive bladder cancer investigated by cystoscopy or transurethral resection.
  
  
  METHODS
  An electronic database search of Medline, Embase, the Cochrane Library, and CancerLit was undertaken, plus hand searching of relevant congress abstracts and urologic journals. Trials were included if they prospectively compared WLC with PDD in bladder cancer. The review process followed the guidelines of the Cochrane Collaboration. Two reviewers evaluated independently both trial eligibility and methodological quality and data extraction.
  
  
  RESULTS
  The primary end point of diagnostic accuracy was additional detection rate. The primary end points of therapeutic outcome were residual tumour at second resection and recurrence-free survival (RFS). Seventeen trials were identified. Twelve diagnostic trials used WLC and PDD with the same patients. Seven reported results for the subgroup of patients with carcinoma in situ (CIS). Five randomised trials studied therapeutic outcome. The results were combined in random effects meta-analyses if end points, designs, and populations were comparable. Twenty percent (95% confidence interval [CI], 8-35) more tumour-positive patients were detected with PDD in all patients with non-muscle-invasive tumours and 39% (CI, 23-57) more when only CIS was analysed. Heterogeneity was present among diagnostic studies even when the subgroup of patients with CIS was investigated. Residual tumour was significantly less often found after PDD (odds ratio: 0.28; 95% CI, 0.15-0.52; p<0.0001). RFS was higher at 12 and 24 mo in the PDD groups than in the WLC-only groups. The combined p value of log-rank tests of RFS was statistically significant (0.00002).
  
  
  CONCLUSIONS
  PDD detects more bladder tumour-positive patients, especially more with CIS, than WLC. More patients have a complete resection and a longer RFS when diagnosed with PDD.
authors.affiliation: Department of Urology, University at Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany. Ingo.Kausch@uk-sh.de
authors.forename: Ingo
authors.initials: I
authors.lastname: Kausch
authors.forename: Martin
authors.initials: M
authors.lastname: Sommerauer
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Didier
authors.initials: D
authors.lastname: Jacqmin
authors.forename: Patrice
authors.initials: P
authors.lastname: Jichlinski
authors.forename: Dieter
authors.initials: D
authors.lastname: Jocham
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Reinhard
authors.initials: R
authors.lastname: Vonthein
mesh_terms: D000622:Aminolevulinic Acid / Q000031:analogs & derivatives*; D015653:Cystectomy; D003558:Cystoscopy; D018572:Disease-Free Survival; D019317:Evidence-Based Medicine; D006801:Humans; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000601:surgery
chemical_list: D000622:Aminolevulinic Acid; C419924:5-aminolevulinic acid hexyl ester