title: Disease-free survival as a surrogate for overall survival in upper tract urothelial carcinoma.
abstract: OBJECTIVE
  The primary endpoint in trials of perioperative systemic therapy for urothelial carcinoma is 5-year overall survival (OS). A shorter-term endpoint could significantly speed the translation of advances into practice. We hypothesized that disease-free survival (DFS) could be a surrogate endpoint for OS in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU).
  
  
  METHODS
  The study included 2,492 patients treated with RNU with curative intent for UTUC.
  
  
  RESULTS
  2/3-year DFS estimates were 78/73 %, and the 5-year OS estimate was 64 %. The overall agreements between 2- and 3-year DFS with 5-year OS were 85 and 87 %, respectively. Agreements were similar when analyzed in subgroups stratified by pathological stages, lymph node status, and adjuvant chemotherapy. The kappa statistic was 0.59 (95 % CI 0.55-0.63) for 2-year DFS/5-year OS and 0.64 (95 % CI 0.61-0.68) for 3-year DFS/5-year OS, indicating moderate reliability. The hazard ratio for DFS as a time-dependent variable for predicting OS was 11.5 (95 % CI 9.1-14.4), indicating a strong relationship between DFS and OS.
  
  
  CONCLUSIONS
  In patients treated with RNU for UTUC, DFS and OS are highly correlated, regardless of tumor stage and adjuvant chemotherapy. While significant differences in DFS, assessed at 2 and 3 years, are highly likely to persist in OS at 5 years, marginal DFS advantages may not translate into OS benefit. External validation is necessary before accepting DFS as an appropriate surrogate endpoint for clinical trials investigating advanced UTUC patients.
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, 525 East 68th St., Starr 900, New York, NY 10065, USA.
authors.forename: Harun
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authors.forename: Quoc-Dien
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authors.initials: PI
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authors.forename: Vitaly
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authors.lastname: Margulis
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authors.forename: Francesco
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authors.forename: Wassim
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authors.lastname: Kassouf
authors.forename: Hans-Martin
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authors.lastname: Fritsche
authors.forename: Karim
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authors.lastname: Bensalah
authors.forename: Richard
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authors.lastname: Zigeuner
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Scherr
authors.forename: Guru
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authors.initials: SF
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mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000401:mortality* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000401:mortality* / Q000601:surgery; D007682:Kidney Pelvis; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014513:Ureter / Q000601:surgery; D014516:Ureteral Neoplasms / Q000401:mortality* / Q000601:surgery