Combination of Multiple Molecular Markers Can Improve Prognostication in Patients With Locally Advanced and Lymph Node Positive Bladder Cancer

Shahrokh F. Shariat, Daher C. Chade, Pierre I. Karakiewicz, Raheela Ashfaq, Hendrik Isbarn, Yves Fradet, Patrick J. Bastian, Matthew E. Nielsen, Umberto Capitanio, Claudio Jeldres, Francesco Montorsi, Seth P. Lerner, Arthur I. Sagalowsky, Richard J Cote, Yair Lotan

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Purpose: We tested whether the combination of 4 established cell cycle regulators (p53, pRB, p21 and p27) could improve the ability to predict clinical outcomes in a large multi-institutional collaboration of patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder. We also assessed whether the combination of molecular markers is superior to any individual biomarker. Materials and Methods: The study comprised 692 patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder treated with radical cystectomy and bilateral lymphadenectomy (median followup 5.3 years). Scoring was performed using advanced cell imaging and color detection software. The base model incorporated patient age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of positive lymph nodes, concomitant carcinoma in situ and adjuvant chemotherapy. Results: Individual molecular markers did not improve the predictive accuracy for disease recurrence and cancer specific mortality. Combination of all 4 molecular markers into number of altered molecular markers resulted in significantly higher predictive accuracy than any single biomarker (p <0.001). Moreover addition of number of altered molecular markers to the base model significantly improved the predictive accuracy for disease recurrence (3.9%, p <0.001) and cancer specific mortality (4.3%, p <0.001). Addition of number of altered molecular markers retained statistical significance for improving the prediction of clinical outcomes in the subgroup of patients with pT3N0 (280), pT4N0 (83) and pTany Npositive (329) disease (p <0.001). Conclusions: While the status of individual molecular markers does not add sufficient value to outcome prediction in patients with advanced urothelial carcinoma of the bladder, combinations of molecular markers may improve molecular staging, prognostication and possibly prediction of response to therapy.

Original languageEnglish
Pages (from-to)68-75
Number of pages8
JournalJournal of Urology
Volume183
Issue number1
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

Fingerprint

Urinary Bladder Neoplasms
Lymph Nodes
Urinary Bladder
Carcinoma
Biomarkers
Recurrence
Mortality
Cystectomy
Carcinoma in Situ
Adjuvant Chemotherapy
Lymph Node Excision
Neoplasms
Cell Cycle
Software
Color
Therapeutics

Keywords

  • biological markers
  • immunohistochemistry
  • recurrence
  • survival
  • urinary bladder neoplasms

ASJC Scopus subject areas

  • Urology

Cite this

Combination of Multiple Molecular Markers Can Improve Prognostication in Patients With Locally Advanced and Lymph Node Positive Bladder Cancer. / Shariat, Shahrokh F.; Chade, Daher C.; Karakiewicz, Pierre I.; Ashfaq, Raheela; Isbarn, Hendrik; Fradet, Yves; Bastian, Patrick J.; Nielsen, Matthew E.; Capitanio, Umberto; Jeldres, Claudio; Montorsi, Francesco; Lerner, Seth P.; Sagalowsky, Arthur I.; Cote, Richard J; Lotan, Yair.

In: Journal of Urology, Vol. 183, No. 1, 01.01.2010, p. 68-75.

Research output: Contribution to journalArticle

Shariat, SF, Chade, DC, Karakiewicz, PI, Ashfaq, R, Isbarn, H, Fradet, Y, Bastian, PJ, Nielsen, ME, Capitanio, U, Jeldres, C, Montorsi, F, Lerner, SP, Sagalowsky, AI, Cote, RJ & Lotan, Y 2010, 'Combination of Multiple Molecular Markers Can Improve Prognostication in Patients With Locally Advanced and Lymph Node Positive Bladder Cancer', Journal of Urology, vol. 183, no. 1, pp. 68-75. https://doi.org/10.1016/j.juro.2009.08.115
Shariat, Shahrokh F. ; Chade, Daher C. ; Karakiewicz, Pierre I. ; Ashfaq, Raheela ; Isbarn, Hendrik ; Fradet, Yves ; Bastian, Patrick J. ; Nielsen, Matthew E. ; Capitanio, Umberto ; Jeldres, Claudio ; Montorsi, Francesco ; Lerner, Seth P. ; Sagalowsky, Arthur I. ; Cote, Richard J ; Lotan, Yair. / Combination of Multiple Molecular Markers Can Improve Prognostication in Patients With Locally Advanced and Lymph Node Positive Bladder Cancer. In: Journal of Urology. 2010 ; Vol. 183, No. 1. pp. 68-75.
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AU - Shariat, Shahrokh F.

AU - Chade, Daher C.

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 - Lerner, Seth P.

AU - Sagalowsky, Arthur I.

AU - Cote, Richard J

AU - Lotan, Yair

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