title: Diagnosis and management of urothelial carcinoma in situ of the lower urinary tract: a systematic review.
abstract: BACKGROUND
  Urothelial carcinoma in situ (CIS) has a high propensity for progression. It is usually reported within the heterogeneous context of non-muscle-invasive bladder cancer (NMIBC) but warrants special consideration.
  
  
  OBJECTIVE
  To review the contemporary literature on the diagnosis and management of CIS.
  
  
  METHODS
  A systematic search using broad terms to capture the diagnosis and treatment of CIS was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria. Full-text original articles, reviews, and editorials from 1966 to 2014 in English were included. References from selected articles, relevant guidelines, and conference abstracts were searched. Abstracts were excluded.
  
  
  RESULTS
  A total of 1887 articles were identified, of which 120 were used in this review. Most reports were retrospective and heterogeneous in caseload. There is a lack of standardised classification of CIS. Many studies consider CIS in the context of NMIBC without a clear separation of the subset with CIS. Recent prospective phase 2 and 3 studies have improved the evidence base.
  
  
  CONCLUSIONS
  We are beginning to understand that CIS has a spectrum of biologic potential. Bacillus Calmette-Guérin immunotherapy appears superior to other intravesical agents and may alter the natural history of CIS. New imaging modalities, agents, and treatment strategies have emerged in recent years with the aim of better identification of CIS, more bladder-preserving treatments, and prevention of surgical overtreatment.
  
  
  RESULTS
  Improvements in imaging techniques combined with new bladder-preserving treatments will continue to have an impact on the outcomes of bladder carcinoma in situ.
authors.affiliation: Department of Urology, Essex Cancer Centre, Colchester General Hospital, Colchester, UK.
authors.forename: Rowan G
authors.initials: RG
authors.lastname: Casey
authors.affiliation: Academic Urology Unit, University of Sheffield, Sheffield, UK.
authors.forename: James W F
authors.initials: JW
authors.lastname: Catto
authors.affiliation: Departments of Pathology and Urology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Urology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Cookson
authors.affiliation: Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Harry
authors.initials: H
authors.lastname: Herr
authors.affiliation: Department of Urology, Medical University of Vienna and Weill Cornell Medical College, New York, NY, USA.
authors.forename: Sharokh
authors.initials: S
authors.lastname: Shariat
authors.affiliation: Department of Oncological Urology, University Hospital Nijmegen, Nijmegen, The Netherlands.
authors.forename: J Alfred
authors.initials: JA
authors.lastname: Witjes
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: pblack@mail.ubc.ca.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Black
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000283:Administration, Intravesical; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000628:therapy*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D064847:Multimodal Imaging; D016896:Treatment Outcome; D014551:Urinary Tract / Q000187:drug effects / Q000473:pathology*; D014571:Urologic Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy*
chemical_list: D000276:Adjuvants, Immunologic
keywords: Bacillus Calmette-Guérin; Bladder; Fluorescent cystoscopy; Gemcitabine; Hyperthermia; Interferon-α; Intravesical immunotherapy; Narrow-band cystoscopy; Photodynamic diagnosis; Urothelial carcinoma in situ; Valrubicin