title: Disease-free survival at 2 or 3 years correlates with 5-year overall survival of patients undergoing radical cystectomy for muscle invasive bladder cancer.
abstract: OBJECTIVE
  The conventional primary end point in trials of perioperative systemic therapy for muscle invasive bladder cancer is 5-year overall survival. We identified an association between disease-free survival at 2 to 3 years and 5-year overall survival.
  
  
  METHODS
  We retrospectively analyzed a multicenter database containing records of 2,724 patients treated with radical cystectomy for muscle invasive bladder cancer with negative margins. Of these patients 844 had received adjuvant chemotherapy. We evaluated the association of disease-free survival at 2 and 3 years with overall survival at 5 years using Cox proportional hazards modeling and the kappa statistic.
  
  
  RESULTS
  Overall 2-year/3-year disease-free survival was 0.63/0.57 and 5-year overall survival was 0.47. The overall agreement between 2-year disease-free survival and 5-year overall survival was 79%, and between 3-year disease-free survival and 5-year overall survival was 81%. Agreements were similar when analyzed within pathological substages, radical cystectomy decades and adjuvant chemotherapy subgroups. The kappa statistic was 0.57 (95% CI 0.53-0.60) for 2-year disease-free survival/5-year overall survival and 0.61 (95% CI 0.58-0.64) for 3-year disease-free survival/5-year overall survival, indicating moderate agreement. The hazard ratio for disease-free survival as a time dependent variable was 12.7 (95% CI 11.60-13.90), indicating a strong relationship between disease-free and overall survival.
  
  
  CONCLUSIONS
  Disease-free survival rates at 2 and 3 years correlate with and are potential intermediate surrogates for 5-year overall survival in patients treated with radical cystectomy for muscle invasive bladder cancer regardless of adjuvant chemotherapy. These data warrant external validation and may expedite the development of adjuvant systemic therapy. In addition, they may be applicable to the neoadjuvant setting.
authors.affiliation: Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA. gurus@bcm.edu
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.forename: Myrna M
authors.initials: MM
authors.lastname: Khan
authors.forename: Seth P
authors.initials: SP
authors.lastname: Lerner
authors.forename: Robert S
authors.initials: RS
authors.lastname: Svatek
authors.forename: Giacomo
authors.initials: G
authors.lastname: Novara
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Eila
authors.initials: E
authors.lastname: Skinner
authors.forename: Derya
authors.initials: D
authors.lastname: Tilki
authors.forename: Wassim
authors.initials: W
authors.lastname: Kassouf
authors.forename: Yves
authors.initials: Y
authors.lastname: Fradet
authors.forename: Colin P
authors.initials: CP
authors.lastname: Dinney
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Fritsche
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Izawa
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bastian
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ficarra
authors.forename: Mark
authors.initials: M
authors.lastname: Schoenberg
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Sagalowsky
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000401:mortality* / Q000473:pathology / Q000601:surgery*; D015331:Cohort Studies; D016001:Confidence Intervals; D015653:Cystectomy / Q000379:methods* / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery*; D055815:Young Adult