p53 Predictive Value for pT1-2 N0 Disease at Radical Cystectomy

Shahrokh F. Shariat, Yair Lotan, Pierre I. Karakiewicz, Raheela Ashfaq, Hendrik Isbarn, Yves Fradet, Patrick J. Bastian, Matthew E. Nielsen, Umberto Capitanio, Claudio Jeldres, Francesco Montorsi, Stefan C. Müller, Jose A. Karam, Lukas C. Heukamp, George Netto, Seth P. Lerner, Arthur I Sagalowsky, Richard J. Cote

Research output: Contribution to journalArticle

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Abstract

Purpose: Approximately 15% to 30% of patients with pT1-2N0M0 urothelial carcinoma of the bladder experience disease progression despite radical cystectomy with curative intent. We determined whether p53 expression would improve the prediction of disease progression after radical cystectomy for pT1-2N0M0 UCB. Materials and Methods: In a multi-institutional retrospective cohort we identified 324 patients with pT1-2N0M0 urothelial carcinoma of the bladder who underwent radical cystectomy. Analysis focused on a testing cohort of 272 patients and an external validation of 52. Competing risks regression models were used to test the association of variables with cancer specific mortality after accounting for nonbladder cancer caused mortality. Results: In the testing cohort 91 patients (33.5%) had altered p53 expression (p53alt). On multivariate competing risks regression analysis altered p53 achieved independent status for predicting disease recurrence and cancer specific mortality (each p <0.001). Adding p53 increased the accuracy of multivariate competing risks regression models predicting recurrence and cancer specific mortality by 5.7% (62.0% vs 67.7%) and 5.4% (61.6% vs 67.0%), respectively. Conclusions: Alterations in p53 represent a highly promising marker of disease recurrence and cancer specific mortality after radical cystectomy for urothelial carcinoma of the bladder. Analysis confirmed previous findings and showed that considering p53 can result in substantial accuracy gains relative to the use of standard predictors. The value and the level of the current evidence clearly exceed previous proof of the independent predictor status of p53 for predicting recurrence and cancer specific mortality.

Original languageEnglish (US)
Pages (from-to)907-913
Number of pages7
JournalJournal of Urology
Volume182
Issue number3
DOIs
StatePublished - Sep 2009

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Cystectomy
Mortality
Recurrence
Neoplasms
Carcinoma
Disease Progression
Urinary Bladder
Urinary Bladder Diseases
Regression Analysis

Keywords

  • carcinoma
  • genes
  • mortality
  • p53
  • urinary bladder
  • urothelium

ASJC Scopus subject areas

  • Urology

Cite this

Shariat, S. F., Lotan, Y., Karakiewicz, P. I., Ashfaq, R., Isbarn, H., Fradet, Y., ... Cote, R. J. (2009). p53 Predictive Value for pT1-2 N0 Disease at Radical Cystectomy. Journal of Urology, 182(3), 907-913. https://doi.org/10.1016/j.juro.2009.05.024

p53 Predictive Value for pT1-2 N0 Disease at Radical Cystectomy. / Shariat, Shahrokh F.; Lotan, Yair; Karakiewicz, Pierre I.; Ashfaq, Raheela; Isbarn, Hendrik; Fradet, Yves; Bastian, Patrick J.; Nielsen, Matthew E.; Capitanio, Umberto; Jeldres, Claudio; Montorsi, Francesco; Müller, Stefan C.; Karam, Jose A.; Heukamp, Lukas C.; Netto, George; Lerner, Seth P.; Sagalowsky, Arthur I; Cote, Richard J.

In: Journal of Urology, Vol. 182, No. 3, 09.2009, p. 907-913.

Research output: Contribution to journalArticle

Shariat, SF, Lotan, Y, Karakiewicz, PI, Ashfaq, R, Isbarn, H, Fradet, Y, Bastian, PJ, Nielsen, ME, Capitanio, U, Jeldres, C, Montorsi, F, Müller, SC, Karam, JA, Heukamp, LC, Netto, G, Lerner, SP, Sagalowsky, AI & Cote, RJ 2009, 'p53 Predictive Value for pT1-2 N0 Disease at Radical Cystectomy', Journal of Urology, vol. 182, no. 3, pp. 907-913. https://doi.org/10.1016/j.juro.2009.05.024
Shariat SF, Lotan Y, Karakiewicz PI, Ashfaq R, Isbarn H, Fradet Y et al. p53 Predictive Value for pT1-2 N0 Disease at Radical Cystectomy. Journal of Urology. 2009 Sep;182(3):907-913. https://doi.org/10.1016/j.juro.2009.05.024
Shariat, Shahrokh F. ; Lotan, Yair ; Karakiewicz, Pierre I. ; Ashfaq, Raheela ; Isbarn, Hendrik ; Fradet, Yves ; Bastian, Patrick J. ; Nielsen, Matthew E. ; Capitanio, Umberto ; Jeldres, Claudio ; Montorsi, Francesco ; Müller, Stefan C. ; Karam, Jose A. ; Heukamp, Lukas C. ; Netto, George ; Lerner, Seth P. ; Sagalowsky, Arthur I ; Cote, Richard J. / p53 Predictive Value for pT1-2 N0 Disease at Radical Cystectomy. In: Journal of Urology. 2009 ; Vol. 182, No. 3. pp. 907-913.
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AU - Shariat, Shahrokh F.

AU - Lotan, Yair

AU - Karakiewicz, Pierre I.

AU - Ashfaq, Raheela

AU - Isbarn, Hendrik

AU - Fradet, Yves

AU - Bastian, Patrick J.

AU - Nielsen, Matthew E.

AU - Capitanio, Umberto

AU - Jeldres, Claudio

AU - Montorsi, Francesco

AU - Müller, Stefan C.

AU - Karam, Jose A.

AU - Heukamp, Lukas C.

AU - Netto, George

AU - Lerner, Seth P.

AU - Sagalowsky, Arthur I

AU - Cote, Richard J.

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N2 - Purpose: Approximately 15% to 30% of patients with pT1-2N0M0 urothelial carcinoma of the bladder experience disease progression despite radical cystectomy with curative intent. We determined whether p53 expression would improve the prediction of disease progression after radical cystectomy for pT1-2N0M0 UCB. Materials and Methods: In a multi-institutional retrospective cohort we identified 324 patients with pT1-2N0M0 urothelial carcinoma of the bladder who underwent radical cystectomy. Analysis focused on a testing cohort of 272 patients and an external validation of 52. Competing risks regression models were used to test the association of variables with cancer specific mortality after accounting for nonbladder cancer caused mortality. Results: In the testing cohort 91 patients (33.5%) had altered p53 expression (p53alt). On multivariate competing risks regression analysis altered p53 achieved independent status for predicting disease recurrence and cancer specific mortality (each p <0.001). Adding p53 increased the accuracy of multivariate competing risks regression models predicting recurrence and cancer specific mortality by 5.7% (62.0% vs 67.7%) and 5.4% (61.6% vs 67.0%), respectively. Conclusions: Alterations in p53 represent a highly promising marker of disease recurrence and cancer specific mortality after radical cystectomy for urothelial carcinoma of the bladder. Analysis confirmed previous findings and showed that considering p53 can result in substantial accuracy gains relative to the use of standard predictors. The value and the level of the current evidence clearly exceed previous proof of the independent predictor status of p53 for predicting recurrence and cancer specific mortality.

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