title: Significance of downstaging in muscle-invasive bladder cancer treated with preoperative radiotherapy.
abstract: OBJECTIVE
  The relationship between clinical-to-pathologic downstaging and patient outcome following preoperative radiotherapy was examined, focusing on the mechanism (selection vs. treatment effect) responsible for the benefit seen from such downstaging.
  
  
  METHODS
  Three hundred and one patients were treated with preoperative radiotherapy plus cystectomy (PREOP) to a median dose of 50 Gy in 25 fractions between 1960-1983. These patients were compared to 225 patients treated with radical cystectomy, with or without chemotherapy (CYST), between 1984-1990. Multiagent chemotherapy was given to 68% of those in the CYST group and was not given to any in the PREOP group. Lymph node involvement was not formally evaluated in the PREOP group, while 20% had pathologic involvement in the CYST group.
  
  
  RESULTS
  Clinical-to-pathologic downstaging (P < T stage) was found in 73% treated with PREOP and 29% treated with CYST (p < 0.0001, chi-square). The only factors that correlated with P < T staging for the PREOP and CYST groups when each was considered separately were clinical stage, blood urea nitrogen level, and creatinine level (p < 0.05, chi-square). Multivariate logistic regression revealed that treatment (PREOP vs. CYST) correlated independently with P < T staging (p < 0.0001). The relationship of actuarial local control to distant metastasis at 5 years in patients that were downstaged, as stratified by clinical stage and treatment, was then examined. Local control rates for P < T staged T2/T3a patients were independent of treatment (PREOP vs. CYST), while distant metastasis rates were significantly greater for those in the PREOP group. In contrast, P < T staged T3b patients in the PREOP group had significantly better local control and distant metastasis rates.
  
  
  CONCLUSIONS
  Significantly higher P < T staging rates were observed with PREOP as compared to CYST, and this was a consequence of the radiotherapy given. The relationship of downstaging from radiotherapy to local control and distant metastasis was contingent on clinical stage. The results of Stage T2/T3a and T3b patients were divergent and supported treatment effect, rather than selection, as the mechanism consistent with the patient outcomes observed.
authors.affiliation: Department of Radiotherapy, University of Texas, M. D. Anderson Cancer Center, Houston, USA.
authors.forename: A
authors.initials: A
authors.lastname: Pollack
authors.forename: G K
authors.initials: GK
authors.lastname: Zagars
authors.forename: C J
authors.initials: CJ
authors.lastname: Cole
authors.forename: C P
authors.initials: CP
authors.lastname: Dinney
authors.forename: D A
authors.initials: DA
authors.lastname: Swanson
authors.forename: H B
authors.initials: HB
authors.lastname: Grossman
mesh_terms: D000328:Adult; D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000473:pathology* / Q000532:radiotherapy* / Q000556:secondary / Q000601:surgery; D003131:Combined Modality Therapy; D015653:Cystectomy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D001749:Urinary Bladder Neoplasms / Q000473:pathology* / Q000532:radiotherapy* / Q000601:surgery