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 Kassouf & 7 others Hans Martin Fritsche, Karim Bensalah, Richard Zigeuner, Douglas S. Scherr, Guru Sonpavde, Morgan Roupret, Shahrokh F. Shariat

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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
Volume31
Issue number1
DOIs
StatePublished - 2013

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Disease-Free Survival
Carcinoma
Survival
Adjuvant Chemotherapy
Biomarkers
Lymph Nodes
Clinical Trials

Keywords

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

ASJC Scopus subject areas

  • Urology

Cite this

Fajkovic, H., Cha, E. K., Xylinas, E., Rink, M., Pycha, A., Seitz, C., ... Shariat, S. F. (2013). Disease-free survival as a surrogate for overall survival in upper tract urothelial carcinoma. World Journal of Urology, 31(1), 5-11. https://doi.org/10.1007/s00345-012-0939-5

Disease-free survival as a surrogate for overall survival in upper tract urothelial carcinoma. / Fajkovic, Harun; Cha, Eugene K.; Xylinas, Evanguelos; Rink, Michael; Pycha, Armin; Seitz, Christian; Bolenz, Christian; Dunning, Allison; Novara, Giacomo; Trinh, Quoc Dien; Karakiewicz, Pierre I.; Margulis, Vitaly; Raman, Jay D.; Walton, Thomas J.; Baba, Shiro; Carballido, Joaquin; Otto, Wolfgang; Montorsi, Francesco; Lotan, Yair; Kassouf, Wassim; Fritsche, Hans Martin; Bensalah, Karim; Zigeuner, Richard; Scherr, Douglas S.; Sonpavde, Guru; Roupret, Morgan; Shariat, Shahrokh F.

In: World Journal of Urology, Vol. 31, No. 1, 2013, p. 5-11.

Research output: Contribution to journalArticle

Fajkovic, H, Cha, EK, Xylinas, E, Rink, M, Pycha, A, Seitz, C, Bolenz, C, Dunning, A, Novara, G, Trinh, QD, Karakiewicz, PI, Margulis, V, Raman, JD, Walton, TJ, Baba, S, Carballido, J, Otto, W, Montorsi, F, Lotan, Y, Kassouf, W, Fritsche, HM, Bensalah, K, Zigeuner, R, Scherr, DS, Sonpavde, G, Roupret, M & Shariat, SF 2013, 'Disease-free survival as a surrogate for overall survival in upper tract urothelial carcinoma', World Journal of Urology, vol. 31, no. 1, pp. 5-11. https://doi.org/10.1007/s00345-012-0939-5
Fajkovic, Harun ; Cha, Eugene K. ; Xylinas, Evanguelos ; Rink, Michael ; Pycha, Armin ; Seitz, Christian ; Bolenz, Christian ; Dunning, Allison ; Novara, Giacomo ; Trinh, Quoc Dien ; Karakiewicz, Pierre I. ; Margulis, Vitaly ; Raman, Jay D. ; Walton, Thomas J. ; Baba, Shiro ; Carballido, Joaquin ; Otto, Wolfgang ; Montorsi, Francesco ; Lotan, Yair ; Kassouf, Wassim ; Fritsche, Hans Martin ; Bensalah, Karim ; Zigeuner, Richard ; Scherr, Douglas S. ; Sonpavde, Guru ; Roupret, Morgan ; Shariat, Shahrokh F. / Disease-free survival as a surrogate for overall survival in upper tract urothelial carcinoma. In: World Journal of Urology. 2013 ; Vol. 31, No. 1. pp. 5-11.
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abstract = "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.",
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T1 - Disease-free survival as a surrogate for overall survival in upper tract urothelial carcinoma

AU - Fajkovic, Harun

AU - Cha, Eugene K.

AU - Xylinas, Evanguelos

AU - Rink, Michael

AU - Pycha, Armin

AU - Seitz, Christian

AU - Bolenz, Christian

AU - Dunning, Allison

AU - Novara, Giacomo

AU - Trinh, Quoc Dien

AU - Karakiewicz, Pierre I.

AU - Margulis, Vitaly

AU - Raman, Jay D.

AU - Walton, Thomas J.

AU - Baba, Shiro

AU - Carballido, Joaquin

AU - Otto, Wolfgang

AU - Montorsi, Francesco

AU - Lotan, Yair

AU - Kassouf, Wassim

AU - Fritsche, Hans Martin

AU - Bensalah, Karim

AU - Zigeuner, Richard

AU - Scherr, Douglas S.

AU - Sonpavde, Guru

AU - Roupret, Morgan

AU - Shariat, Shahrokh F.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Disease-free survival

KW - Overall survival

KW - Recurrence

KW - Surrogacy

KW - Upper tract urothelial carcinoma

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