title: External validation of disease-free survival at 2 or 3 years as a surrogate and new primary endpoint for patients undergoing radical cystectomy for urothelial carcinoma of the bladder.
abstract: OBJECTIVE
  To perform the first external validation of a recently identified association between disease-free survival at two years (DFS2) or three years (DFS3) and overall survival at five years (OS5) in patients after radical cystectomy (RC) for muscle-invasive urothelial carcinoma of the bladder (UCB).
  
  
  METHODS
  Records of 2483 patients who underwent RC for UCB at eight European centers between 1989 and 2008 were reviewed. The cohort included 1738 patients with pT2-4a tumors and negative soft tissue surgical margins (STSM) according to the selection criteria of the previous study (study group (SG)). In addition, 745 patients with positive STSM or other tumor stages (pT0-T1, pT4b) that were excluded from the previous study (excluded patient group (EPG)) were evaluated. Kappa statistic was used to measure the agreement between DFS2 or DFS3 and OS5.
  
  
  RESULTS
  The overall agreement between DFS2 and OS5 was 86.5% (EPG: 88.7%) and 90.1% (EPG: 92.1%) between DFS3 and OS5. The kappa values for comparison of DFS2 or DFS3 with OS5 were 0.73 (SE: 0.016) and 0.80 (SE: 0.014) respectively for the SG, and 0.67 (SE: 0.033) and 0.78 (SE: 0.027) for the EPG (all p-values <0.001).
  
  
  CONCLUSIONS
  We externally validated a correlation between DFS2 or DFS3 and OS5 for patients with pT2-4a UCB with negative STSM that underwent RC. Furthermore, this correlation was found in patients with other tumor stages regardless of STSM status. These findings indicate DFS2 and DFS3 as valid surrogate markers for survival outcome with RC.
authors.affiliation: Department of Urology, Klinikum der Universität München - Campus Großhadern, Ludwig-Maximilians-Universität, Marchioninistr. 15, 81377 Munich, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Nuhn
authors.forename: M
authors.initials: M
authors.lastname: May
authors.forename: H-M
authors.initials: HM
authors.lastname: Fritsche
authors.forename: A
authors.initials: A
authors.lastname: Buchner
authors.forename: S
authors.initials: S
authors.lastname: Brookman-May
authors.forename: C
authors.initials: C
authors.lastname: Bolenz
authors.forename: R
authors.initials: R
authors.lastname: Moritz
authors.forename: E
authors.initials: E
authors.lastname: Herrmann
authors.forename: M
authors.initials: M
authors.lastname: Burger
authors.forename: T
authors.initials: T
authors.lastname: Höfner
authors.forename: J
authors.initials: J
authors.lastname: Ellinger
authors.forename: D
authors.initials: D
authors.lastname: Tilki
authors.forename: J
authors.initials: J
authors.lastname: Roigas
authors.forename: M
authors.initials: M
authors.lastname: Zacharias
authors.forename: L
authors.initials: L
authors.lastname: Trojan
authors.forename: C
authors.initials: C
authors.lastname: Wülfing
authors.forename: F
authors.initials: F
authors.lastname: May
authors.forename: S
authors.initials: S
authors.lastname: Melchior
authors.forename: A
authors.initials: A
authors.lastname: Haferkamp
authors.forename: C
authors.initials: C
authors.lastname: Gilfrich
authors.forename: M
authors.initials: M
authors.lastname: Hohenfellner
authors.forename: W F
authors.initials: WF
authors.lastname: Wieland
authors.forename: S C
authors.initials: SC
authors.lastname: Müller
authors.forename: C G
authors.initials: CG
authors.lastname: Stief
authors.forename: P J
authors.initials: PJ
authors.lastname: Bastian
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000401:mortality* / Q000556:secondary / Q000601:surgery*; D015331:Cohort Studies; D015653:Cystectomy / Q000379:methods; D018572:Disease-Free Survival; D023381:Endpoint Determination; D005060:Europe; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery*; D019459:Urothelium / Q000473:pathology / Q000601:surgery