title: Multi-institutional validation of the predictive value of Ki-67 labeling index in patients with urinary bladder cancer.
abstract: Several small single-center studies have reported a prognostic role for Ki-67 labeling index in advanced urothelial carcinoma of the urinary bladder. To investigate whether Ki-67 was a useful biomarker of oncological outcome after radical cystectomy for urothelial carcinoma, we assessed its expression in tumor tissue from 713 patients treated with radical cystectomy and bilateral lymphadenectomy at six centers. A high Ki-67 labeling index was independently associated with established features of aggressive urothelial carcinoma, disease recurrence, and cancer-specific survival. Addition of Ki-67 labeling index improved the accuracy of standard multivariate outcome prediction models, as measured by Harrell concordance index, by 2.9% for disease recurrence and 2.4% for bladder cancer-specific survival (P < .001, two-sided Mantel-Haenszel) -- a statistically and potentially clinically significant margin. In conclusion, routine assessment of Ki-67 expression status along with assessment of other established predictors of urothelial carcinoma outcome has the potential to improve identification of patients who are at increased risk for disease progression after radical cystectomy and thus may benefit from perioperative systemic chemotherapy.
authors.affiliation: Department of Urologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Yves
authors.initials: Y
authors.lastname: Fradet
authors.forename: Raheela
authors.initials: R
authors.lastname: Ashfaq
authors.forename: Umberto
authors.initials: U
authors.lastname: Capitanio
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bastian
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Nielsen
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.forename: Jérôme
authors.initials: J
authors.lastname: Rigaud
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Heukamp
authors.forename: George
authors.initials: G
authors.lastname: Netto
authors.forename: Seth P
authors.initials: SP
authors.lastname: Lerner
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Sagalowsky
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
mesh_terms: D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000276:immunology* / Q000601:surgery; D015653:Cystectomy; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis*; D008197:Lymph Node Excision; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D015983:Selection Bias; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D019459:Urothelium / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen