Multi-institutional validation of the predictive value of Ki-67 labeling index in patients with urinary bladder cancer

J Natl Cancer Inst. 2009 Jan 21;101(2):114-9. doi: 10.1093/jnci/djn451. Epub 2009 Jan 13.


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.

Publication types

  • Multicenter Study
  • Validation Study

MeSH terms

  • Analysis of Variance
  • Biomarkers, Tumor / analysis*
  • Carcinoma / immunology*
  • Carcinoma / surgery
  • Cystectomy*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / analysis*
  • Lymph Node Excision
  • Predictive Value of Tests
  • Prognosis
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Factors
  • Selection Bias
  • Urinary Bladder Neoplasms / immunology*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery
  • Urothelium / pathology


  • Biomarkers, Tumor
  • Ki-67 Antigen