Predicting clinical outcomes after radical nephroureterectomy for upper tract urothelial carcinoma

Eugene K. Cha, Shahrokh F. Shariat, Matthias Kormaksson, Giacomo Novara, Thomas F. Chromecki, Douglas S. Scherr, Yair Lotan, Jay D. Raman, Wassim Kassouf, Richard Zigeuner, Mesut Remzi, Karim Bensalah, Alon Weizer, Eiji Kikuchi, Christian Bolenz, Marco Roscigno, Theresa M. Koppie, Casey K. Ng, Hans Martin Fritsche, Kazumasa Matsumoto & 13 others Thomas J. Walton, Behfar Ehdaie, Stefan Tritschler, Harun Fajkovic, Juan I. Martínez-Salamanca, Armin Pycha, Cord Langner, Vincenzo Ficarra, Jean Jacques Patard, Francesco Montorsi, Christopher G. Wood, Pierre I. Karakiewicz, Vitaly Margulis

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Background: Novel prognostic factors for patients after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) have recently been described. Objective: We tested the prognostic value of pathologic characteristics and developed models to predict the individual probabilities of recurrence-free survival (RFS) and cancer-specific survival (CSS) after RNU. Design, setting, and participants: Our study included 2244 patients treated with RNU without neoadjuvant or adjuvant therapy at 23 international institutions. Tumor characteristics included T classification, grade, lymph node status, lymphovascular invasion, tumor architecture, location, and concomitant carcinoma in situ (CIS). The cohort was randomly split for development (12 centers, n = 1273) and external validation (11 centers, n = 971). Interventions: All patients underwent RNU. Measurements: Univariable and multivariable models addressed RFS, CSS, and comparison of discrimination and calibration with American Joint Committee on Cancer (AJCC) stage grouping. Results and limitations: At a median follow-up of 45 mo, 501 patients (22.3%) experienced disease recurrence and 418 patients (18.6%) died of UTUC. On multivariable analysis, T classification (p for trend <0.001), lymph node metastasis (hazard ratio [HR]: 1.98; p = 0.002), lymphovascular invasion (HR: 1.66; p < 0.001), sessile tumor architecture (HR: 1.76; p < 0.001), and concomitant CIS (HR: 1.33; p = 0.035) were associated with disease recurrence. Similarly, T classification (p for trend < 0.001), lymph node metastasis (HR: 2.23; p = 0.001), lymphovascular invasion (HR: 1.81; p < 0.001), and sessile tumor architecture (HR: 1.72; p = 0.001) were independently associated with cancer-specific mortality. Our models achieved 76.8% and 81.5% accuracy for predicting RFS and CSS, respectively. In contrast to these well-calibrated models, stratification based upon AJCC stage grouping resulted in a large degree of heterogeneity and did not improve discrimination. Conclusions: Using standard pathologic features, we developed highly accurate prognostic models for the prediction of RFS and CSS after RNU for UTUC. These models offer improvements in calibration over AJCC stage grouping and can be used for individualized patient counseling, follow-up scheduling, risk stratification for adjuvant therapies, and inclusion criteria for clinical trials.

Original languageEnglish
Pages (from-to)818-825
Number of pages8
JournalEuropean Urology
Volume61
Issue number4
DOIs
Publication statusPublished - 2012 Apr

Fingerprint

Carcinoma
Neoplasms
Survival
Recurrence
Lymph Nodes
Carcinoma in Situ
Calibration
Neoplasm Metastasis
Counseling
Clinical Trials
Mortality
Therapeutics

Keywords

  • Nephroureterectomy
  • Nomogram
  • Survival prediction
  • Upper urinary tract
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Urology

Cite this

Cha, E. K., Shariat, S. F., Kormaksson, M., Novara, G., Chromecki, T. F., Scherr, D. S., ... Margulis, V. (2012). Predicting clinical outcomes after radical nephroureterectomy for upper tract urothelial carcinoma. European Urology, 61(4), 818-825. https://doi.org/10.1016/j.eururo.2012.01.021

Predicting clinical outcomes after radical nephroureterectomy for upper tract urothelial carcinoma. / Cha, Eugene K.; Shariat, Shahrokh F.; Kormaksson, Matthias; Novara, Giacomo; Chromecki, Thomas F.; Scherr, Douglas S.; Lotan, Yair; Raman, Jay D.; Kassouf, Wassim; Zigeuner, Richard; Remzi, Mesut; Bensalah, Karim; Weizer, Alon; Kikuchi, Eiji; Bolenz, Christian; Roscigno, Marco; Koppie, Theresa M.; Ng, Casey K.; Fritsche, Hans Martin; Matsumoto, Kazumasa; Walton, Thomas J.; Ehdaie, Behfar; Tritschler, Stefan; Fajkovic, Harun; Martínez-Salamanca, Juan I.; Pycha, Armin; Langner, Cord; Ficarra, Vincenzo; Patard, Jean Jacques; Montorsi, Francesco; Wood, Christopher G.; Karakiewicz, Pierre I.; Margulis, Vitaly.

In: European Urology, Vol. 61, No. 4, 04.2012, p. 818-825.

Research output: Contribution to journalArticle

Cha, EK, Shariat, SF, Kormaksson, M, Novara, G, Chromecki, TF, Scherr, DS, Lotan, Y, Raman, JD, Kassouf, W, Zigeuner, R, Remzi, M, Bensalah, K, Weizer, A, Kikuchi, E, Bolenz, C, Roscigno, M, Koppie, TM, Ng, CK, Fritsche, HM, Matsumoto, K, Walton, TJ, Ehdaie, B, Tritschler, S, Fajkovic, H, Martínez-Salamanca, JI, Pycha, A, Langner, C, Ficarra, V, Patard, JJ, Montorsi, F, Wood, CG, Karakiewicz, PI & Margulis, V 2012, 'Predicting clinical outcomes after radical nephroureterectomy for upper tract urothelial carcinoma', European Urology, vol. 61, no. 4, pp. 818-825. https://doi.org/10.1016/j.eururo.2012.01.021
Cha, Eugene K. ; Shariat, Shahrokh F. ; Kormaksson, Matthias ; Novara, Giacomo ; Chromecki, Thomas F. ; Scherr, Douglas S. ; Lotan, Yair ; Raman, Jay D. ; Kassouf, Wassim ; Zigeuner, Richard ; Remzi, Mesut ; Bensalah, Karim ; Weizer, Alon ; Kikuchi, Eiji ; Bolenz, Christian ; Roscigno, Marco ; Koppie, Theresa M. ; Ng, Casey K. ; Fritsche, Hans Martin ; Matsumoto, Kazumasa ; Walton, Thomas J. ; Ehdaie, Behfar ; Tritschler, Stefan ; Fajkovic, Harun ; Martínez-Salamanca, Juan I. ; Pycha, Armin ; Langner, Cord ; Ficarra, Vincenzo ; Patard, Jean Jacques ; Montorsi, Francesco ; Wood, Christopher G. ; Karakiewicz, Pierre I. ; Margulis, Vitaly. / Predicting clinical outcomes after radical nephroureterectomy for upper tract urothelial carcinoma. In: European Urology. 2012 ; Vol. 61, No. 4. pp. 818-825.
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abstract = "Background: Novel prognostic factors for patients after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) have recently been described. Objective: We tested the prognostic value of pathologic characteristics and developed models to predict the individual probabilities of recurrence-free survival (RFS) and cancer-specific survival (CSS) after RNU. Design, setting, and participants: Our study included 2244 patients treated with RNU without neoadjuvant or adjuvant therapy at 23 international institutions. Tumor characteristics included T classification, grade, lymph node status, lymphovascular invasion, tumor architecture, location, and concomitant carcinoma in situ (CIS). The cohort was randomly split for development (12 centers, n = 1273) and external validation (11 centers, n = 971). Interventions: All patients underwent RNU. Measurements: Univariable and multivariable models addressed RFS, CSS, and comparison of discrimination and calibration with American Joint Committee on Cancer (AJCC) stage grouping. Results and limitations: At a median follow-up of 45 mo, 501 patients (22.3{\%}) experienced disease recurrence and 418 patients (18.6{\%}) died of UTUC. On multivariable analysis, T classification (p for trend <0.001), lymph node metastasis (hazard ratio [HR]: 1.98; p = 0.002), lymphovascular invasion (HR: 1.66; p < 0.001), sessile tumor architecture (HR: 1.76; p < 0.001), and concomitant CIS (HR: 1.33; p = 0.035) were associated with disease recurrence. Similarly, T classification (p for trend < 0.001), lymph node metastasis (HR: 2.23; p = 0.001), lymphovascular invasion (HR: 1.81; p < 0.001), and sessile tumor architecture (HR: 1.72; p = 0.001) were independently associated with cancer-specific mortality. Our models achieved 76.8{\%} and 81.5{\%} accuracy for predicting RFS and CSS, respectively. In contrast to these well-calibrated models, stratification based upon AJCC stage grouping resulted in a large degree of heterogeneity and did not improve discrimination. Conclusions: Using standard pathologic features, we developed highly accurate prognostic models for the prediction of RFS and CSS after RNU for UTUC. These models offer improvements in calibration over AJCC stage grouping and can be used for individualized patient counseling, follow-up scheduling, risk stratification for adjuvant therapies, and inclusion criteria for clinical trials.",
keywords = "Nephroureterectomy, Nomogram, Survival prediction, Upper urinary tract, Urothelial carcinoma",
author = "Cha, {Eugene K.} and Shariat, {Shahrokh F.} and Matthias Kormaksson and Giacomo Novara and Chromecki, {Thomas F.} and Scherr, {Douglas S.} and Yair Lotan and Raman, {Jay D.} and Wassim Kassouf and Richard Zigeuner and Mesut Remzi and Karim Bensalah and Alon Weizer and Eiji Kikuchi and Christian Bolenz and Marco Roscigno and Koppie, {Theresa M.} and Ng, {Casey K.} and Fritsche, {Hans Martin} and Kazumasa Matsumoto and Walton, {Thomas J.} and Behfar Ehdaie and Stefan Tritschler and Harun Fajkovic and Mart{\'i}nez-Salamanca, {Juan I.} and Armin Pycha and Cord Langner and Vincenzo Ficarra and Patard, {Jean Jacques} and Francesco Montorsi and Wood, {Christopher G.} and Karakiewicz, {Pierre I.} and Vitaly Margulis",
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TY - JOUR

T1 - Predicting clinical outcomes after radical nephroureterectomy for upper tract urothelial carcinoma

AU - Cha, Eugene K.

AU - Shariat, Shahrokh F.

AU - Kormaksson, Matthias

AU - Novara, Giacomo

AU - Chromecki, Thomas F.

AU - Scherr, Douglas S.

AU - Lotan, Yair

AU - Raman, Jay D.

AU - Kassouf, Wassim

AU - Zigeuner, Richard

AU - Remzi, Mesut

AU - Bensalah, Karim

AU - Weizer, Alon

AU - Kikuchi, Eiji

AU - Bolenz, Christian

AU - Roscigno, Marco

AU - Koppie, Theresa M.

AU - Ng, Casey K.

AU - Fritsche, Hans Martin

AU - Matsumoto, Kazumasa

AU - Walton, Thomas J.

AU - Ehdaie, Behfar

AU - Tritschler, Stefan

AU - Fajkovic, Harun

AU - Martínez-Salamanca, Juan I.

AU - Pycha, Armin

AU - Langner, Cord

AU - Ficarra, Vincenzo

AU - Patard, Jean Jacques

AU - Montorsi, Francesco

AU - Wood, Christopher G.

AU - Karakiewicz, Pierre I.

AU - Margulis, Vitaly

PY - 2012/4

Y1 - 2012/4

N2 - Background: Novel prognostic factors for patients after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) have recently been described. Objective: We tested the prognostic value of pathologic characteristics and developed models to predict the individual probabilities of recurrence-free survival (RFS) and cancer-specific survival (CSS) after RNU. Design, setting, and participants: Our study included 2244 patients treated with RNU without neoadjuvant or adjuvant therapy at 23 international institutions. Tumor characteristics included T classification, grade, lymph node status, lymphovascular invasion, tumor architecture, location, and concomitant carcinoma in situ (CIS). The cohort was randomly split for development (12 centers, n = 1273) and external validation (11 centers, n = 971). Interventions: All patients underwent RNU. Measurements: Univariable and multivariable models addressed RFS, CSS, and comparison of discrimination and calibration with American Joint Committee on Cancer (AJCC) stage grouping. Results and limitations: At a median follow-up of 45 mo, 501 patients (22.3%) experienced disease recurrence and 418 patients (18.6%) died of UTUC. On multivariable analysis, T classification (p for trend <0.001), lymph node metastasis (hazard ratio [HR]: 1.98; p = 0.002), lymphovascular invasion (HR: 1.66; p < 0.001), sessile tumor architecture (HR: 1.76; p < 0.001), and concomitant CIS (HR: 1.33; p = 0.035) were associated with disease recurrence. Similarly, T classification (p for trend < 0.001), lymph node metastasis (HR: 2.23; p = 0.001), lymphovascular invasion (HR: 1.81; p < 0.001), and sessile tumor architecture (HR: 1.72; p = 0.001) were independently associated with cancer-specific mortality. Our models achieved 76.8% and 81.5% accuracy for predicting RFS and CSS, respectively. In contrast to these well-calibrated models, stratification based upon AJCC stage grouping resulted in a large degree of heterogeneity and did not improve discrimination. Conclusions: Using standard pathologic features, we developed highly accurate prognostic models for the prediction of RFS and CSS after RNU for UTUC. These models offer improvements in calibration over AJCC stage grouping and can be used for individualized patient counseling, follow-up scheduling, risk stratification for adjuvant therapies, and inclusion criteria for clinical trials.

AB - Background: Novel prognostic factors for patients after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) have recently been described. Objective: We tested the prognostic value of pathologic characteristics and developed models to predict the individual probabilities of recurrence-free survival (RFS) and cancer-specific survival (CSS) after RNU. Design, setting, and participants: Our study included 2244 patients treated with RNU without neoadjuvant or adjuvant therapy at 23 international institutions. Tumor characteristics included T classification, grade, lymph node status, lymphovascular invasion, tumor architecture, location, and concomitant carcinoma in situ (CIS). The cohort was randomly split for development (12 centers, n = 1273) and external validation (11 centers, n = 971). Interventions: All patients underwent RNU. Measurements: Univariable and multivariable models addressed RFS, CSS, and comparison of discrimination and calibration with American Joint Committee on Cancer (AJCC) stage grouping. Results and limitations: At a median follow-up of 45 mo, 501 patients (22.3%) experienced disease recurrence and 418 patients (18.6%) died of UTUC. On multivariable analysis, T classification (p for trend <0.001), lymph node metastasis (hazard ratio [HR]: 1.98; p = 0.002), lymphovascular invasion (HR: 1.66; p < 0.001), sessile tumor architecture (HR: 1.76; p < 0.001), and concomitant CIS (HR: 1.33; p = 0.035) were associated with disease recurrence. Similarly, T classification (p for trend < 0.001), lymph node metastasis (HR: 2.23; p = 0.001), lymphovascular invasion (HR: 1.81; p < 0.001), and sessile tumor architecture (HR: 1.72; p = 0.001) were independently associated with cancer-specific mortality. Our models achieved 76.8% and 81.5% accuracy for predicting RFS and CSS, respectively. In contrast to these well-calibrated models, stratification based upon AJCC stage grouping resulted in a large degree of heterogeneity and did not improve discrimination. Conclusions: Using standard pathologic features, we developed highly accurate prognostic models for the prediction of RFS and CSS after RNU for UTUC. These models offer improvements in calibration over AJCC stage grouping and can be used for individualized patient counseling, follow-up scheduling, risk stratification for adjuvant therapies, and inclusion criteria for clinical trials.

KW - Nephroureterectomy

KW - Nomogram

KW - Survival prediction

KW - Upper urinary tract

KW - Urothelial carcinoma

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