Extranodal extension is a powerful prognostic factor in bladder cancer patients with lymph node metastasis

Harun Fajkovic, Eugene K. Cha, Claudio Jeldres, Brian D. Robinson, Michael Rink, Evanguelos Xylinas, Thomas F. Chromecki, Eckart Breinl, Robert Svatek, Gerhard Donner, Scott T. Tagawa, Derya Tilki, Patrick J. Bastian, Pierre I. Karakiewicz, Bjoern G. Volkmer, Giacomo Novara, Abdennabi Joual, Talia Faison, Guru Sonpavde, Siamak DaneshmandYair Lotan, Douglas S. Scherr, Shahrokh F. Shariat

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Original languageEnglish
Pages (from-to)837-845
Number of pages9
JournalEuropean Urology
Volume64
Issue number5
DOIs
StatePublished - Nov 2013

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Urinary Bladder Neoplasms
Lymph Nodes
Neoplasm Metastasis
Cystectomy
Recurrence
Neoplasms
Mortality
Lymph Node Excision
Confidence Intervals
Neoadjuvant Therapy
Adjuvant Chemotherapy
Counseling
Urinary Bladder
Regression Analysis
Clinical Trials
Carcinoma

ASJC Scopus subject areas

  • Urology

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Fajkovic, H., Cha, E. K., Jeldres, C., Robinson, B. D., Rink, M., Xylinas, E., ... Shariat, S. F. (2013). Extranodal extension is a powerful prognostic factor in bladder cancer patients with lymph node metastasis. European Urology, 64(5), 837-845. https://doi.org/10.1016/j.eururo.2012.07.026

Extranodal extension is a powerful prognostic factor in bladder cancer patients with lymph node metastasis. / Fajkovic, Harun; Cha, Eugene K.; Jeldres, Claudio; Robinson, Brian D.; Rink, Michael; Xylinas, Evanguelos; Chromecki, Thomas F.; Breinl, Eckart; Svatek, Robert; Donner, Gerhard; Tagawa, Scott T.; Tilki, Derya; Bastian, Patrick J.; Karakiewicz, Pierre I.; Volkmer, Bjoern G.; Novara, Giacomo; Joual, Abdennabi; Faison, Talia; Sonpavde, Guru; Daneshmand, Siamak; Lotan, Yair; Scherr, Douglas S.; Shariat, Shahrokh F.

In: European Urology, Vol. 64, No. 5, 11.2013, p. 837-845.

Research output: Contribution to journalArticle

Fajkovic, H, Cha, EK, Jeldres, C, Robinson, BD, Rink, M, Xylinas, E, Chromecki, TF, Breinl, E, Svatek, R, Donner, G, Tagawa, ST, Tilki, D, Bastian, PJ, Karakiewicz, PI, Volkmer, BG, Novara, G, Joual, A, Faison, T, Sonpavde, G, Daneshmand, S, Lotan, Y, Scherr, DS & Shariat, SF 2013, 'Extranodal extension is a powerful prognostic factor in bladder cancer patients with lymph node metastasis', European Urology, vol. 64, no. 5, pp. 837-845. https://doi.org/10.1016/j.eururo.2012.07.026
Fajkovic, Harun ; Cha, Eugene K. ; Jeldres, Claudio ; Robinson, Brian D. ; Rink, Michael ; Xylinas, Evanguelos ; Chromecki, Thomas F. ; Breinl, Eckart ; Svatek, Robert ; Donner, Gerhard ; Tagawa, Scott T. ; Tilki, Derya ; Bastian, Patrick J. ; Karakiewicz, Pierre I. ; Volkmer, Bjoern G. ; Novara, Giacomo ; Joual, Abdennabi ; Faison, Talia ; Sonpavde, Guru ; Daneshmand, Siamak ; Lotan, Yair ; Scherr, Douglas S. ; Shariat, Shahrokh F. / Extranodal extension is a powerful prognostic factor in bladder cancer patients with lymph node metastasis. In: European Urology. 2013 ; Vol. 64, No. 5. pp. 837-845.
@article{97a0bb163e0a4fd9a8c369314ad990a9,
title = "Extranodal extension is a powerful prognostic factor in bladder cancer patients with lymph node metastasis",
abstract = "Background Lymph node metastasis (LNM) is the most powerful pathologic predictor of disease recurrence after radical cystectomy (RC). However, the outcomes of patients with LNM are highly variable. Objective To assess the prognostic value of extranodal extension (ENE) and other lymph node (LN) parameters. Design, setting, and participants A retrospective analysis of 748 patients with urothelial carcinoma of the bladder and LNM treated with RC and lymphadenectomy without neoadjuvant therapy at 10 European and North American centers (median follow-up: 27 mo). Intervention All subjects underwent RC and bilateral pelvic lymphadenectomy. Outcome measurements and statistical analysis Each LNM was microscopically evaluated for the presence of ENE. The number of LNs removed, number of positive LNs, and LN density were recorded and calculated. Univariable and multivariable analyses addressed time to disease recurrence and cancer-specific mortality after RC. Results and limitations A total of 375 patients (50.1{\%}) had ENE. The median number of LNs removed, number of positive LNs, and LN density were 15, 2, and 15, respectively. The rate of ENE increased with advancing pT stage (p < 0.001). In multivariable Cox regression analyses that adjusted for the effects of established clinicopathologic features and LN parameters, ENE was associated with disease recurrence (hazard ratio [HR]: 1.89; 95{\%} confidence interval [CI], 1.55-2.31; p < 0.001) and cancer-specific mortality (HR: 1.90; 95{\%} CI, 1.52-2.37; p < 0.001). The addition of ENE to a multivariable model that included pT stage, tumor grade, age, gender, lymphovascular invasion, surgical margin status, LN density, number of LNs removed, number of positive LNs, and adjuvant chemotherapy improved predictive accuracy for disease recurrence and cancer-specific mortality from 70.3{\%} to 77.8{\%} (p < 0.001) and from 71.8{\%} to 77.8{\%} (p = 0.007), respectively. The main limitation of the study is its retrospective nature. Conclusions ENE is an independent predictor of both cancer recurrence and cancer-specific mortality in RC patients with LNM. Knowledge of ENE status could help with patient counseling, clinical decision making regarding inclusion in clinical trials of adjuvant therapy, and tailored follow-up scheduling after RC.",
keywords = "Bladder cancer, Extranodal extension, Lymph node metastasis, Prognosis, Recurrence, Survival, Urothelial carcinoma",
author = "Harun Fajkovic and Cha, {Eugene K.} and Claudio Jeldres and Robinson, {Brian D.} and Michael Rink and Evanguelos Xylinas and Chromecki, {Thomas F.} and Eckart Breinl and Robert Svatek and Gerhard Donner and Tagawa, {Scott T.} and Derya Tilki and Bastian, {Patrick J.} and Karakiewicz, {Pierre I.} and Volkmer, {Bjoern G.} and Giacomo Novara and Abdennabi Joual and Talia Faison and Guru Sonpavde and Siamak Daneshmand and Yair Lotan and Scherr, {Douglas S.} and Shariat, {Shahrokh F.}",
year = "2013",
month = "11",
doi = "10.1016/j.eururo.2012.07.026",
language = "English",
volume = "64",
pages = "837--845",
journal = "European Urology",
issn = "0302-2838",
publisher = "Elsevier",
number = "5",

}

TY - JOUR

T1 - Extranodal extension is a powerful prognostic factor in bladder cancer patients with lymph node metastasis

AU - Fajkovic, Harun

AU - Cha, Eugene K.

AU - Jeldres, Claudio

AU - Robinson, Brian D.

AU - Rink, Michael

AU - Xylinas, Evanguelos

AU - Chromecki, Thomas F.

AU - Breinl, Eckart

AU - Svatek, Robert

AU - Donner, Gerhard

AU - Tagawa, Scott T.

AU - Tilki, Derya

AU - Bastian, Patrick J.

AU - Karakiewicz, Pierre I.

AU - Volkmer, Bjoern G.

AU - Novara, Giacomo

AU - Joual, Abdennabi

AU - Faison, Talia

AU - Sonpavde, Guru

AU - Daneshmand, Siamak

AU - Lotan, Yair

AU - Scherr, Douglas S.

AU - Shariat, Shahrokh F.

PY - 2013/11

Y1 - 2013/11

N2 - Background Lymph node metastasis (LNM) is the most powerful pathologic predictor of disease recurrence after radical cystectomy (RC). However, the outcomes of patients with LNM are highly variable. Objective To assess the prognostic value of extranodal extension (ENE) and other lymph node (LN) parameters. Design, setting, and participants A retrospective analysis of 748 patients with urothelial carcinoma of the bladder and LNM treated with RC and lymphadenectomy without neoadjuvant therapy at 10 European and North American centers (median follow-up: 27 mo). Intervention All subjects underwent RC and bilateral pelvic lymphadenectomy. Outcome measurements and statistical analysis Each LNM was microscopically evaluated for the presence of ENE. The number of LNs removed, number of positive LNs, and LN density were recorded and calculated. Univariable and multivariable analyses addressed time to disease recurrence and cancer-specific mortality after RC. Results and limitations A total of 375 patients (50.1%) had ENE. The median number of LNs removed, number of positive LNs, and LN density were 15, 2, and 15, respectively. The rate of ENE increased with advancing pT stage (p < 0.001). In multivariable Cox regression analyses that adjusted for the effects of established clinicopathologic features and LN parameters, ENE was associated with disease recurrence (hazard ratio [HR]: 1.89; 95% confidence interval [CI], 1.55-2.31; p < 0.001) and cancer-specific mortality (HR: 1.90; 95% CI, 1.52-2.37; p < 0.001). The addition of ENE to a multivariable model that included pT stage, tumor grade, age, gender, lymphovascular invasion, surgical margin status, LN density, number of LNs removed, number of positive LNs, and adjuvant chemotherapy improved predictive accuracy for disease recurrence and cancer-specific mortality from 70.3% to 77.8% (p < 0.001) and from 71.8% to 77.8% (p = 0.007), respectively. The main limitation of the study is its retrospective nature. Conclusions ENE is an independent predictor of both cancer recurrence and cancer-specific mortality in RC patients with LNM. Knowledge of ENE status could help with patient counseling, clinical decision making regarding inclusion in clinical trials of adjuvant therapy, and tailored follow-up scheduling after RC.

AB - Background Lymph node metastasis (LNM) is the most powerful pathologic predictor of disease recurrence after radical cystectomy (RC). However, the outcomes of patients with LNM are highly variable. Objective To assess the prognostic value of extranodal extension (ENE) and other lymph node (LN) parameters. Design, setting, and participants A retrospective analysis of 748 patients with urothelial carcinoma of the bladder and LNM treated with RC and lymphadenectomy without neoadjuvant therapy at 10 European and North American centers (median follow-up: 27 mo). Intervention All subjects underwent RC and bilateral pelvic lymphadenectomy. Outcome measurements and statistical analysis Each LNM was microscopically evaluated for the presence of ENE. The number of LNs removed, number of positive LNs, and LN density were recorded and calculated. Univariable and multivariable analyses addressed time to disease recurrence and cancer-specific mortality after RC. Results and limitations A total of 375 patients (50.1%) had ENE. The median number of LNs removed, number of positive LNs, and LN density were 15, 2, and 15, respectively. The rate of ENE increased with advancing pT stage (p < 0.001). In multivariable Cox regression analyses that adjusted for the effects of established clinicopathologic features and LN parameters, ENE was associated with disease recurrence (hazard ratio [HR]: 1.89; 95% confidence interval [CI], 1.55-2.31; p < 0.001) and cancer-specific mortality (HR: 1.90; 95% CI, 1.52-2.37; p < 0.001). The addition of ENE to a multivariable model that included pT stage, tumor grade, age, gender, lymphovascular invasion, surgical margin status, LN density, number of LNs removed, number of positive LNs, and adjuvant chemotherapy improved predictive accuracy for disease recurrence and cancer-specific mortality from 70.3% to 77.8% (p < 0.001) and from 71.8% to 77.8% (p = 0.007), respectively. The main limitation of the study is its retrospective nature. Conclusions ENE is an independent predictor of both cancer recurrence and cancer-specific mortality in RC patients with LNM. Knowledge of ENE status could help with patient counseling, clinical decision making regarding inclusion in clinical trials of adjuvant therapy, and tailored follow-up scheduling after RC.

KW - Bladder cancer

KW - Extranodal extension

KW - Lymph node metastasis

KW - Prognosis

KW - Recurrence

KW - Survival

KW - Urothelial carcinoma

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U2 - 10.1016/j.eururo.2012.07.026

DO - 10.1016/j.eururo.2012.07.026

M3 - Article

C2 - 22877503

AN - SCOPUS:84885420539

VL - 64

SP - 837

EP - 845

JO - European Urology

JF - European Urology

SN - 0302-2838

IS - 5

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