Prediction of intravesical recurrence after radical nephroureterectomy: Development of a clinical decision-making tool

Evanguelos Xylinas, Luis Kluth, Niccolo Passoni, Quoc Dien Trinh, Malte Rieken, Richard K. Lee, Harun Fajkovic, Giacomo Novara, Vitaly Margulis, Jay D. Raman, Yair Lotan, Morgan Rouprêt, Atiqullah Aziz, Hans Martin Fritsche, Alon Weizer, Juan I. Martinez-Salamanca, Kazumasa Matsumoto, Christian Seitz, Mesut Remzi, Thomas WaltonPierre I. Karakiewicz, Francesco Montorsi, Marc Zerbib, Douglas S. Scherr, Shahrokh F. Shariat

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Abstract

Background Intravesical recurrence after radical nephroureterectomy (RNU) is a frequent event requiring intense cystoscopic surveillance. Recently, a prospective randomized clinical trial has shown that a single intravesical postoperative dose of mitomycin C (MMC) reduces the absolute risk of intravesical recurrence after RNU. Objective The aim of the current study was to identify predictors of intravesical recurrence and to develop a tool to allow a risk-stratified approach supporting patient counseling for cystoscopic surveillance and postoperative intravesical MMC administration. Design, setting, and participants We performed a retrospective analysis of 1839 patients with upper tract urothelial carcinoma (UTUC). The data set was split into a development cohort of 1261 patients from North America and a validation cohort of 578 patients from Europe. Interventions RNU with bladder cuff excision was performed. The surgical approach was open in 1424 patients (77.4%) and laparoscopic in 415 patients (22.6%). Outcome measurements and statistical analyses Univariable and multivariable Cox regression models addressed time to intravesical recurrence after RNU. We developed a nomogram for prediction of the probability of intravesical recurrence at 3, 6, 9, 12, 18, 24, and 36 mo. Predictive accuracy was quantified using the concordance index. Decision curve analysis was performed to evaluate the clinical benefit associated with the use of our nomograms. Results and limitations With a median follow-up of 45 mo, intravesical recurrence occurred in 577 patients (31%). The probability of intravesical recurrence-free survival at 6, 12, 24, and 36 mo was 85% ± 1%, 78% ± 1%, 68% ± 1%, and 47% ± 2%, respectively. In multivariable Cox regression analysis, advanced age, male gender, ureteral tumor location, laparoscopic surgical technique, endoscopic distal ureteral management, previous bladder cancer, higher tumor stage, concomitant carcinoma in situ, and lymph node involvement were all significantly associated with intravesical recurrence (p values ≤0.04). The nomograms were highly accurate for predicting intravesical recurrence in the external validation cohort (concordance index of 67.8% and 69.0% for the reduced model and the full model, respectively), and calibration plots revealed only minor overestimation beyond 24 mo. If one decided to perform postoperative instillation based on the risk of intravesical recurrence of 15% at 24 mo, one would spare 23% of the patients while not preventing only 0.3% of intravesical recurrences. The lack of information on the stage and grade of the intravesical recurrences is the main limitation of the study. Conclusions Intravesical recurrence after RNU is a common event in patients with UTUC. We developed nomograms that predict intravesical recurrence after RNU with reasonable accuracy. Such nomograms could improve the clinical decision-making process with regard to cystoscopic surveillance scheduling and postoperative intravesical instillations of MMC after RNU.

Original languageEnglish
Pages (from-to)650-658
Number of pages9
JournalEuropean Urology
Volume65
Issue number3
DOIs
Publication statusPublished - Mar 2014

Fingerprint

Recurrence
Nomograms
Mitomycin
Clinical Decision-Making
Intravesical Administration
Carcinoma
Decision Support Techniques
Carcinoma in Situ
North America
Proportional Hazards Models
Urinary Bladder Neoplasms
Calibration
Counseling
Neoplasms
Urinary Bladder
Randomized Controlled Trials
Lymph Nodes
Regression Analysis
Survival

Keywords

  • Decision curve analysis
  • Intravesical recurrence
  • Nomogram
  • Prediction
  • Radical nephroureterectomy
  • Upper tract urothelial carcinoma

ASJC Scopus subject areas

  • Urology

Cite this

Xylinas, E., Kluth, L., Passoni, N., Trinh, Q. D., Rieken, M., Lee, R. K., ... Shariat, S. F. (2014). Prediction of intravesical recurrence after radical nephroureterectomy: Development of a clinical decision-making tool. European Urology, 65(3), 650-658. https://doi.org/10.1016/j.eururo.2013.09.003

Prediction of intravesical recurrence after radical nephroureterectomy : Development of a clinical decision-making tool. / Xylinas, Evanguelos; Kluth, Luis; Passoni, Niccolo; Trinh, Quoc Dien; Rieken, Malte; Lee, Richard K.; Fajkovic, Harun; Novara, Giacomo; Margulis, Vitaly; Raman, Jay D.; Lotan, Yair; Rouprêt, Morgan; Aziz, Atiqullah; Fritsche, Hans Martin; Weizer, Alon; Martinez-Salamanca, Juan I.; Matsumoto, Kazumasa; Seitz, Christian; Remzi, Mesut; Walton, Thomas; Karakiewicz, Pierre I.; Montorsi, Francesco; Zerbib, Marc; Scherr, Douglas S.; Shariat, Shahrokh F.

In: European Urology, Vol. 65, No. 3, 03.2014, p. 650-658.

Research output: Contribution to journalArticle

Xylinas, E, Kluth, L, Passoni, N, Trinh, QD, Rieken, M, Lee, RK, Fajkovic, H, Novara, G, Margulis, V, Raman, JD, Lotan, Y, Rouprêt, M, Aziz, A, Fritsche, HM, Weizer, A, Martinez-Salamanca, JI, Matsumoto, K, Seitz, C, Remzi, M, Walton, T, Karakiewicz, PI, Montorsi, F, Zerbib, M, Scherr, DS & Shariat, SF 2014, 'Prediction of intravesical recurrence after radical nephroureterectomy: Development of a clinical decision-making tool', European Urology, vol. 65, no. 3, pp. 650-658. https://doi.org/10.1016/j.eururo.2013.09.003
Xylinas, Evanguelos ; Kluth, Luis ; Passoni, Niccolo ; Trinh, Quoc Dien ; Rieken, Malte ; Lee, Richard K. ; Fajkovic, Harun ; Novara, Giacomo ; Margulis, Vitaly ; Raman, Jay D. ; Lotan, Yair ; Rouprêt, Morgan ; Aziz, Atiqullah ; Fritsche, Hans Martin ; Weizer, Alon ; Martinez-Salamanca, Juan I. ; Matsumoto, Kazumasa ; Seitz, Christian ; Remzi, Mesut ; Walton, Thomas ; Karakiewicz, Pierre I. ; Montorsi, Francesco ; Zerbib, Marc ; Scherr, Douglas S. ; Shariat, Shahrokh F. / Prediction of intravesical recurrence after radical nephroureterectomy : Development of a clinical decision-making tool. In: European Urology. 2014 ; Vol. 65, No. 3. pp. 650-658.
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abstract = "Background Intravesical recurrence after radical nephroureterectomy (RNU) is a frequent event requiring intense cystoscopic surveillance. Recently, a prospective randomized clinical trial has shown that a single intravesical postoperative dose of mitomycin C (MMC) reduces the absolute risk of intravesical recurrence after RNU. Objective The aim of the current study was to identify predictors of intravesical recurrence and to develop a tool to allow a risk-stratified approach supporting patient counseling for cystoscopic surveillance and postoperative intravesical MMC administration. Design, setting, and participants We performed a retrospective analysis of 1839 patients with upper tract urothelial carcinoma (UTUC). The data set was split into a development cohort of 1261 patients from North America and a validation cohort of 578 patients from Europe. Interventions RNU with bladder cuff excision was performed. The surgical approach was open in 1424 patients (77.4{\%}) and laparoscopic in 415 patients (22.6{\%}). Outcome measurements and statistical analyses Univariable and multivariable Cox regression models addressed time to intravesical recurrence after RNU. We developed a nomogram for prediction of the probability of intravesical recurrence at 3, 6, 9, 12, 18, 24, and 36 mo. Predictive accuracy was quantified using the concordance index. Decision curve analysis was performed to evaluate the clinical benefit associated with the use of our nomograms. Results and limitations With a median follow-up of 45 mo, intravesical recurrence occurred in 577 patients (31{\%}). The probability of intravesical recurrence-free survival at 6, 12, 24, and 36 mo was 85{\%} ± 1{\%}, 78{\%} ± 1{\%}, 68{\%} ± 1{\%}, and 47{\%} ± 2{\%}, respectively. In multivariable Cox regression analysis, advanced age, male gender, ureteral tumor location, laparoscopic surgical technique, endoscopic distal ureteral management, previous bladder cancer, higher tumor stage, concomitant carcinoma in situ, and lymph node involvement were all significantly associated with intravesical recurrence (p values ≤0.04). The nomograms were highly accurate for predicting intravesical recurrence in the external validation cohort (concordance index of 67.8{\%} and 69.0{\%} for the reduced model and the full model, respectively), and calibration plots revealed only minor overestimation beyond 24 mo. If one decided to perform postoperative instillation based on the risk of intravesical recurrence of 15{\%} at 24 mo, one would spare 23{\%} of the patients while not preventing only 0.3{\%} of intravesical recurrences. The lack of information on the stage and grade of the intravesical recurrences is the main limitation of the study. Conclusions Intravesical recurrence after RNU is a common event in patients with UTUC. We developed nomograms that predict intravesical recurrence after RNU with reasonable accuracy. Such nomograms could improve the clinical decision-making process with regard to cystoscopic surveillance scheduling and postoperative intravesical instillations of MMC after RNU.",
keywords = "Decision curve analysis, Intravesical recurrence, Nomogram, Prediction, Radical nephroureterectomy, Upper tract urothelial carcinoma",
author = "Evanguelos Xylinas and Luis Kluth and Niccolo Passoni and Trinh, {Quoc Dien} and Malte Rieken and Lee, {Richard K.} and Harun Fajkovic and Giacomo Novara and Vitaly Margulis and Raman, {Jay D.} and Yair Lotan and Morgan Roupr{\^e}t and Atiqullah Aziz and Fritsche, {Hans Martin} and Alon Weizer and Martinez-Salamanca, {Juan I.} and Kazumasa Matsumoto and Christian Seitz and Mesut Remzi and Thomas Walton and Karakiewicz, {Pierre I.} and Francesco Montorsi and Marc Zerbib and Scherr, {Douglas S.} and Shariat, {Shahrokh F.}",
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TY - JOUR

T1 - Prediction of intravesical recurrence after radical nephroureterectomy

T2 - Development of a clinical decision-making tool

AU - Xylinas, Evanguelos

AU - Kluth, Luis

AU - Passoni, Niccolo

AU - Trinh, Quoc Dien

AU - Rieken, Malte

AU - Lee, Richard K.

AU - Fajkovic, Harun

AU - Novara, Giacomo

AU - Margulis, Vitaly

AU - Raman, Jay D.

AU - Lotan, Yair

AU - Rouprêt, Morgan

AU - Aziz, Atiqullah

AU - Fritsche, Hans Martin

AU - Weizer, Alon

AU - Martinez-Salamanca, Juan I.

AU - Matsumoto, Kazumasa

AU - Seitz, Christian

AU - Remzi, Mesut

AU - Walton, Thomas

AU - Karakiewicz, Pierre I.

AU - Montorsi, Francesco

AU - Zerbib, Marc

AU - Scherr, Douglas S.

AU - Shariat, Shahrokh F.

PY - 2014/3

Y1 - 2014/3

N2 - Background Intravesical recurrence after radical nephroureterectomy (RNU) is a frequent event requiring intense cystoscopic surveillance. Recently, a prospective randomized clinical trial has shown that a single intravesical postoperative dose of mitomycin C (MMC) reduces the absolute risk of intravesical recurrence after RNU. Objective The aim of the current study was to identify predictors of intravesical recurrence and to develop a tool to allow a risk-stratified approach supporting patient counseling for cystoscopic surveillance and postoperative intravesical MMC administration. Design, setting, and participants We performed a retrospective analysis of 1839 patients with upper tract urothelial carcinoma (UTUC). The data set was split into a development cohort of 1261 patients from North America and a validation cohort of 578 patients from Europe. Interventions RNU with bladder cuff excision was performed. The surgical approach was open in 1424 patients (77.4%) and laparoscopic in 415 patients (22.6%). Outcome measurements and statistical analyses Univariable and multivariable Cox regression models addressed time to intravesical recurrence after RNU. We developed a nomogram for prediction of the probability of intravesical recurrence at 3, 6, 9, 12, 18, 24, and 36 mo. Predictive accuracy was quantified using the concordance index. Decision curve analysis was performed to evaluate the clinical benefit associated with the use of our nomograms. Results and limitations With a median follow-up of 45 mo, intravesical recurrence occurred in 577 patients (31%). The probability of intravesical recurrence-free survival at 6, 12, 24, and 36 mo was 85% ± 1%, 78% ± 1%, 68% ± 1%, and 47% ± 2%, respectively. In multivariable Cox regression analysis, advanced age, male gender, ureteral tumor location, laparoscopic surgical technique, endoscopic distal ureteral management, previous bladder cancer, higher tumor stage, concomitant carcinoma in situ, and lymph node involvement were all significantly associated with intravesical recurrence (p values ≤0.04). The nomograms were highly accurate for predicting intravesical recurrence in the external validation cohort (concordance index of 67.8% and 69.0% for the reduced model and the full model, respectively), and calibration plots revealed only minor overestimation beyond 24 mo. If one decided to perform postoperative instillation based on the risk of intravesical recurrence of 15% at 24 mo, one would spare 23% of the patients while not preventing only 0.3% of intravesical recurrences. The lack of information on the stage and grade of the intravesical recurrences is the main limitation of the study. Conclusions Intravesical recurrence after RNU is a common event in patients with UTUC. We developed nomograms that predict intravesical recurrence after RNU with reasonable accuracy. Such nomograms could improve the clinical decision-making process with regard to cystoscopic surveillance scheduling and postoperative intravesical instillations of MMC after RNU.

AB - Background Intravesical recurrence after radical nephroureterectomy (RNU) is a frequent event requiring intense cystoscopic surveillance. Recently, a prospective randomized clinical trial has shown that a single intravesical postoperative dose of mitomycin C (MMC) reduces the absolute risk of intravesical recurrence after RNU. Objective The aim of the current study was to identify predictors of intravesical recurrence and to develop a tool to allow a risk-stratified approach supporting patient counseling for cystoscopic surveillance and postoperative intravesical MMC administration. Design, setting, and participants We performed a retrospective analysis of 1839 patients with upper tract urothelial carcinoma (UTUC). The data set was split into a development cohort of 1261 patients from North America and a validation cohort of 578 patients from Europe. Interventions RNU with bladder cuff excision was performed. The surgical approach was open in 1424 patients (77.4%) and laparoscopic in 415 patients (22.6%). Outcome measurements and statistical analyses Univariable and multivariable Cox regression models addressed time to intravesical recurrence after RNU. We developed a nomogram for prediction of the probability of intravesical recurrence at 3, 6, 9, 12, 18, 24, and 36 mo. Predictive accuracy was quantified using the concordance index. Decision curve analysis was performed to evaluate the clinical benefit associated with the use of our nomograms. Results and limitations With a median follow-up of 45 mo, intravesical recurrence occurred in 577 patients (31%). The probability of intravesical recurrence-free survival at 6, 12, 24, and 36 mo was 85% ± 1%, 78% ± 1%, 68% ± 1%, and 47% ± 2%, respectively. In multivariable Cox regression analysis, advanced age, male gender, ureteral tumor location, laparoscopic surgical technique, endoscopic distal ureteral management, previous bladder cancer, higher tumor stage, concomitant carcinoma in situ, and lymph node involvement were all significantly associated with intravesical recurrence (p values ≤0.04). The nomograms were highly accurate for predicting intravesical recurrence in the external validation cohort (concordance index of 67.8% and 69.0% for the reduced model and the full model, respectively), and calibration plots revealed only minor overestimation beyond 24 mo. If one decided to perform postoperative instillation based on the risk of intravesical recurrence of 15% at 24 mo, one would spare 23% of the patients while not preventing only 0.3% of intravesical recurrences. The lack of information on the stage and grade of the intravesical recurrences is the main limitation of the study. Conclusions Intravesical recurrence after RNU is a common event in patients with UTUC. We developed nomograms that predict intravesical recurrence after RNU with reasonable accuracy. Such nomograms could improve the clinical decision-making process with regard to cystoscopic surveillance scheduling and postoperative intravesical instillations of MMC after RNU.

KW - Decision curve analysis

KW - Intravesical recurrence

KW - Nomogram

KW - Prediction

KW - Radical nephroureterectomy

KW - Upper tract urothelial carcinoma

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