Disease-free survival as a surrogate for overall survival in upper tract urothelial carcinoma

Harun Fajkovic, Eugene K. Cha, Evanguelos Xylinas, Michael Rink, Armin Pycha, Christian Seitz, Christian Bolenz, Allison Dunning, Giacomo Novara, Quoc Dien Trinh, Pierre I. Karakiewicz, Vitaly Margulis, Jay D. Raman, Thomas J. Walton, Shiro Baba, Joaquin Carballido, Wolfgang Otto, Francesco Montorsi, Yair Lotan, Wassim KassoufHans Martin Fritsche, Karim Bensalah, Richard Zigeuner, Douglas S. Scherr, Guru Sonpavde, Morgan Roupret, Shahrokh F. Shariat

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Objectives: 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). Patients and 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.

Original languageEnglish (US)
Pages (from-to)5-11
Number of pages7
JournalWorld journal of urology
Issue number1
StatePublished - Feb 2013


  • Disease-free survival
  • Overall survival
  • Recurrence
  • Surrogacy
  • Upper tract urothelial carcinoma

ASJC Scopus subject areas

  • Urology


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