title: The prognostic significance of S-phase analysis in stage Ta/T1 bladder cancer. A Southwest Oncology Group Study.
abstract: OBJECTIVE
  An intergroup study (SWOG 8795) comparing two forms of adjunctive therapy (immuno and chemo), bacillus Calmette-Guerin (BCG) and mitomycin C (MMC), furnished preregistration index tumors for 244 patients with superficial, papillary stage Ta/T1 TCC. These were examined by flow cytometry to learn whether DNA ploidy or proliferation (low vs high S-phase fraction (SPF) helped to predict disease recurrence or progression.
  
  
  METHODS
  Cell cycle analysis using commercially available (Multicycle) programs was performed on 249 Ta/T1 bladder cancers. Tumor grade, available for 223 cases, was assigned by a single study pathologist. The SWOG statistical office reviewed follow-up information and other data and performed statistical analysis.
  
  
  RESULTS
  Disease recurrence occurred in half the cases studied. The most parsimonious model predictive of recurrence included only treatment arm and tumor grade, with the MMC arm and tumor grade greater than I indicating worse prognosis (p = 0. 014). Neither ploidy nor SPF predicted recurrence-free survival or contributed prognostic information that was additive to tumor grade. Within 5 years of follow-up, disease progression or death from bladder cancer occurred for 29/223 (13%) of patients. The most parsimonious model for progression-free survival included only grade greater than I (p<0.001) and high SPF (p = 0.029) (relative risk: tumor grade, 4.3, high SPF, 1.9).
  
  
  CONCLUSIONS
  Knowledge of tumor proliferation (low versus high SPF) contributes prognostic information about tumor progression that is additive to tumor grade.
authors.affiliation: University of California, Davis, Sacramento, CA 95817, USA. rwdeverewhite@ucdavis.edu
authors.forename: R W
authors.initials: RW
authors.lastname: deVere White
authors.forename: A D
authors.initials: AD
authors.lastname: Deitch
authors.forename: S
authors.initials: S
authors.lastname: Daneshmand
authors.forename: B
authors.initials: B
authors.lastname: Blumenstein
authors.forename: B A
authors.initials: BA
authors.lastname: Lowe
authors.forename: A I
authors.initials: AI
authors.lastname: Sagalowsky
authors.forename: J A
authors.initials: JA
authors.lastname: Smith
authors.forename: P F
authors.initials: PF
authors.lastname: Schellhammer
authors.forename: T H
authors.initials: TH
authors.lastname: Stanisic
authors.forename: H B
authors.initials: HB
authors.lastname: Grossman
authors.forename: E
authors.initials: E
authors.lastname: Messing
authors.forename: J D
authors.initials: JD
authors.lastname: Crissman
authors.forename: E D
authors.initials: ED
authors.lastname: Crawford
mesh_terms: D002455:Cell Division; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D009367:Neoplasm Staging; D011003:Ploidies; D011379:Prognosis; D016016:Proportional Hazards Models; D016196:S Phase; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*