Critical analysis and validation of lymph node density as prognostic variable in urothelial carcinoma of bladder

Wassim Kassouf, Robert S. Svatek, Shahrokh F. Shariat, Giacomo Novara, Seth P. Lerner, Yves Fradet, Patrick J. Bastian, Armen Aprikian, Pierre I. Karakiewicz, Hans Martin Fritsche, Colin P N Dinney, Derya Tilki, Ashish M. Kamat, Jonathan I. Izawa, Vincenzo Ficarra, Yair Lotan, Arthur I. Sagalowsky, Mark P. Schoenberg, Eila C. Skinner

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Objective:To validate the prognostic relevance of lymph node density (LND) and identify its optimal cut-points in a large international multicenter series of patients treated with radical cystectomy (RC) for invasive bladder cancer. Methods:From 1993 to 2005, 4,430 bladder cancer patients who underwent RC without neoadjuvant chemotherapy were reviewed; of these, 1,038 were pN+M0 disease and form the basis of this report. Results:Median age of patients was 67 years with median follow-up in survivors of 33 months. Overall, 5-year DSS estimate was 36%. Median number of lymph nodes removed was 18 (IQR, 11-32), median number of positive lymph nodes was 2 (IQR, 1-5), and median LND was 14.3% (IQR, 6.67-33.3%). LND as continuous variable was a stronger prognostic factor for DSS in patients that underwent a more extensive PLND (P< 0.001). HR for inverse association of LND with DSS increased incrementally with increasing LND cut-points. Categorizing LND into quintiles revealed strong tertiary distribution of risk based on LND <6%, 6%-41%, or >41% with cumulative 5-year DSS of 47%, 36%, and 21%, respectively (P < 0.001). When patients were stratified by adjuvant chemotherapy, LND remains independently prognostic in patients who received adjuvant chemotherapy as well as those who did not. Conclusion:Lymph node density is prognostic in bladder cancer patients who undergo a more extensive PLND and remains prognostic even when adjuvant chemotherapy is used. Prognostic value of LND is best represented as a continuum of risk and LND <6% represents the best possible outcome in patients with nodal disease.

Original languageEnglish (US)
Pages (from-to)480-486
Number of pages7
JournalUrologic Oncology: Seminars and Original Investigations
Volume31
Issue number4
DOIs
StatePublished - May 2013
Externally publishedYes

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Urinary Bladder
Lymph Nodes
Carcinoma
Adjuvant Chemotherapy
Urinary Bladder Neoplasms
Cystectomy
Survivors
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Critical analysis and validation of lymph node density as prognostic variable in urothelial carcinoma of bladder. / Kassouf, Wassim; Svatek, Robert S.; Shariat, Shahrokh F.; Novara, Giacomo; Lerner, Seth P.; Fradet, Yves; Bastian, Patrick J.; Aprikian, Armen; Karakiewicz, Pierre I.; Fritsche, Hans Martin; Dinney, Colin P N; Tilki, Derya; Kamat, Ashish M.; Izawa, Jonathan I.; Ficarra, Vincenzo; Lotan, Yair; Sagalowsky, Arthur I.; Schoenberg, Mark P.; Skinner, Eila C.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 31, No. 4, 05.2013, p. 480-486.

Research output: Contribution to journalArticle

Kassouf, W, Svatek, RS, Shariat, SF, Novara, G, Lerner, SP, Fradet, Y, Bastian, PJ, Aprikian, A, Karakiewicz, PI, Fritsche, HM, Dinney, CPN, Tilki, D, Kamat, AM, Izawa, JI, Ficarra, V, Lotan, Y, Sagalowsky, AI, Schoenberg, MP & Skinner, EC 2013, 'Critical analysis and validation of lymph node density as prognostic variable in urothelial carcinoma of bladder', Urologic Oncology: Seminars and Original Investigations, vol. 31, no. 4, pp. 480-486. https://doi.org/10.1016/j.urolonc.2011.02.011
Kassouf, Wassim ; Svatek, Robert S. ; Shariat, Shahrokh F. ; Novara, Giacomo ; Lerner, Seth P. ; Fradet, Yves ; Bastian, Patrick J. ; Aprikian, Armen ; Karakiewicz, Pierre I. ; Fritsche, Hans Martin ; Dinney, Colin P N ; Tilki, Derya ; Kamat, Ashish M. ; Izawa, Jonathan I. ; Ficarra, Vincenzo ; Lotan, Yair ; Sagalowsky, Arthur I. ; Schoenberg, Mark P. ; Skinner, Eila C. / Critical analysis and validation of lymph node density as prognostic variable in urothelial carcinoma of bladder. In: Urologic Oncology: Seminars and Original Investigations. 2013 ; Vol. 31, No. 4. pp. 480-486.
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abstract = "Objective:To validate the prognostic relevance of lymph node density (LND) and identify its optimal cut-points in a large international multicenter series of patients treated with radical cystectomy (RC) for invasive bladder cancer. Methods:From 1993 to 2005, 4,430 bladder cancer patients who underwent RC without neoadjuvant chemotherapy were reviewed; of these, 1,038 were pN+M0 disease and form the basis of this report. Results:Median age of patients was 67 years with median follow-up in survivors of 33 months. Overall, 5-year DSS estimate was 36{\%}. Median number of lymph nodes removed was 18 (IQR, 11-32), median number of positive lymph nodes was 2 (IQR, 1-5), and median LND was 14.3{\%} (IQR, 6.67-33.3{\%}). LND as continuous variable was a stronger prognostic factor for DSS in patients that underwent a more extensive PLND (P< 0.001). HR for inverse association of LND with DSS increased incrementally with increasing LND cut-points. Categorizing LND into quintiles revealed strong tertiary distribution of risk based on LND <6{\%}, 6{\%}-41{\%}, or >41{\%} with cumulative 5-year DSS of 47{\%}, 36{\%}, and 21{\%}, respectively (P < 0.001). When patients were stratified by adjuvant chemotherapy, LND remains independently prognostic in patients who received adjuvant chemotherapy as well as those who did not. Conclusion:Lymph node density is prognostic in bladder cancer patients who undergo a more extensive PLND and remains prognostic even when adjuvant chemotherapy is used. Prognostic value of LND is best represented as a continuum of risk and LND <6{\%} represents the best possible outcome in patients with nodal disease.",
author = "Wassim Kassouf and Svatek, {Robert S.} and Shariat, {Shahrokh F.} and Giacomo Novara and Lerner, {Seth P.} and Yves Fradet and Bastian, {Patrick J.} and Armen Aprikian and Karakiewicz, {Pierre I.} and Fritsche, {Hans Martin} and Dinney, {Colin P N} and Derya Tilki and Kamat, {Ashish M.} and Izawa, {Jonathan I.} and Vincenzo Ficarra and Yair Lotan and Sagalowsky, {Arthur I.} and Schoenberg, {Mark P.} and Skinner, {Eila C.}",
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T1 - Critical analysis and validation of lymph node density as prognostic variable in urothelial carcinoma of bladder

AU - Kassouf, Wassim

AU - Svatek, Robert S.

AU - Shariat, Shahrokh F.

AU - Novara, Giacomo

AU - Lerner, Seth P.

AU - Fradet, Yves

AU - Bastian, Patrick J.

AU - Aprikian, Armen

AU - Karakiewicz, Pierre I.

AU - Fritsche, Hans Martin

AU - Dinney, Colin P N

AU - Tilki, Derya

AU - Kamat, Ashish M.

AU - Izawa, Jonathan I.

AU - Ficarra, Vincenzo

AU - Lotan, Yair

AU - Sagalowsky, Arthur I.

AU - Schoenberg, Mark P.

AU - Skinner, Eila C.

PY - 2013/5

Y1 - 2013/5

N2 - Objective:To validate the prognostic relevance of lymph node density (LND) and identify its optimal cut-points in a large international multicenter series of patients treated with radical cystectomy (RC) for invasive bladder cancer. Methods:From 1993 to 2005, 4,430 bladder cancer patients who underwent RC without neoadjuvant chemotherapy were reviewed; of these, 1,038 were pN+M0 disease and form the basis of this report. Results:Median age of patients was 67 years with median follow-up in survivors of 33 months. Overall, 5-year DSS estimate was 36%. Median number of lymph nodes removed was 18 (IQR, 11-32), median number of positive lymph nodes was 2 (IQR, 1-5), and median LND was 14.3% (IQR, 6.67-33.3%). LND as continuous variable was a stronger prognostic factor for DSS in patients that underwent a more extensive PLND (P< 0.001). HR for inverse association of LND with DSS increased incrementally with increasing LND cut-points. Categorizing LND into quintiles revealed strong tertiary distribution of risk based on LND <6%, 6%-41%, or >41% with cumulative 5-year DSS of 47%, 36%, and 21%, respectively (P < 0.001). When patients were stratified by adjuvant chemotherapy, LND remains independently prognostic in patients who received adjuvant chemotherapy as well as those who did not. Conclusion:Lymph node density is prognostic in bladder cancer patients who undergo a more extensive PLND and remains prognostic even when adjuvant chemotherapy is used. Prognostic value of LND is best represented as a continuum of risk and LND <6% represents the best possible outcome in patients with nodal disease.

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