title: Prognostic significance of substage and WHO classification systems in T1 urothelial carcinoma of the bladder.
abstract: OBJECTIVE
  Treatment of T1 urothelial bladder cancer (T1-BC) is challenging as risk assessment criteria for progression are lacking. Histological grade and T1 substage have been identified as important prognostic factors. Currently, no consensus exists regarding the optimal sub-staging and grading systems for T1-BC. We reviewed recent advances in the various grading and sub-staging systems and their clinical applicability.
  
  
  RESULTS
  Stratification by muscularis mucosae invasion is the most explored sub-staging system. Its prognostic value was established by 12/23 (52%) available studies. Importantly, muscularis mucosae identification varied substantially among pathologists. Sub-staging based on diameter of invasive carcinoma [T1 microinvasive and T1 extensive-invasive (T1m/e)] proved a more reproducible system with at least equal prognostic value. However, more study is needed to investigate interobserver variation. For nonmuscle-invasive bladder cancer grading, the 1973 and 2004 WHO classifications both provide independent prognostic information. However, remarkably few studies have investigated their applicability in T1-BC only. The available reports suggest that the 1973 WHO classification is superior to WHO 2004.
  
  
  CONCLUSIONS
  If multicenter studies confirm the promising results of T1m/e sub-staging, it may be incorporated in the Internation Union Against Cancer TNM classification system for urinary bladder cancer. More studies are warranted to define the optimal classification system for grade in T1-BC.
authors.affiliation: aDepartment of Surgical Oncology, Division of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands bDivision of Urology, Department of Surgery, University Hospital of Basel, Basel, Switzerland cDepartment of Urology, VU University Medical Center, Amsterdam, The Netherlands dDepartment of Pathology, University Health Network, Toronto General Hospital, Toronto, Ontario, Canada.
authors.forename: Elisabeth E
authors.initials: EE
authors.lastname: Fransen van de Putte
authors.forename: Mark A
authors.initials: MA
authors.lastname: Behrendt
authors.forename: Garry L S
authors.initials: GL
authors.lastname: Pigot
authors.forename: Theo H
authors.initials: TH
authors.lastname: van der Kwast
authors.forename: Bas W G
authors.initials: BW
authors.lastname: van Rhijn
mesh_terms: D002277:Carcinoma / Q000145:classification / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging / Q000379:methods*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000145:classification / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D019459:Urothelium / Q000473:pathology*