Journal of the National Cancer Institute Advance Access originally published online on January 13, 2009
JNCI Journal of the National Cancer Institute 2009 101(2):114-119; doi:10.1093/jnci/djn451
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© The Author 2009. Published by Oxford University Press.
Multi-Institutional Validation of the Predictive Value of Ki-67 Labeling Index in Patients With Urinary Bladder Cancer
Affiliations of authors: Department of Urologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (VM); Department of Urology (YL, AIS, SFS) and Department of Pathology (RA), University of Texas Southwestern Medical Center, Dallas, TX; Cancer Prognostics and Health Outcomes Unit, University of Montreal, Montreal, Quebec, Canada (PIK, UC); Centre de recherche en cancérologie de l’Université Laval, L’Hôtel-Dieu de Québec, CHUQ, Québec, Canada (YF, JR); Department of Urology, Vita-Salute University, Milan, Italy (UC, FM); Department of Urology (PJB, SCM) and Department of Pathology (MEN, LCH), Rheinische Friedrich-Wilhelms Universität, Bonn, Germany; Department of Urology, Ludwig-Maximilians-Universität München, Munich, Germany (PJB); Department of Urology (MEN, LCH) and Department of Pathology (GN), Johns Hopkins Hospital, Baltimore, MD; Scott Department of Urology, Baylor College of Medicine, Houston, TX (SPL)
Correspondence to: Shahrokh F. Shariat, MD, Sidney Kimmel Center for Prostate and Urologic Cancer Memorial Sloan-Kettering Cancer Center 1275 York Avenue, Box 27 New York, NY 10065 (e-mail: sfshariat{at}gmail.com).
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.
| CONTEXT AND CAVEATS Prior knowledge A high Ki-67 labeling index had been associated with poor clinical outcomes after radical cystectomy for bladder cancer. Study design Regression models were used to assess Ki-67 labeling index as a prognostic marker for disease recurrence and survival in an international, multicenter cohort of patients treated with radical cystectomy and bilateral lymphadenectomy for urothelial bladder cancer. Contribution High Ki-67 labeling index was independently associated with cancer recurrence and survival after radical cystectomy. Addition of the Ki-67 status to multivariate models including standard clinical predictors improved their predictive accuracy, measured by Harrell concordance index, by a statistically significant margin. Limitations Retrospective data collection may have introduced substantial case selection bias, and reproducibility of immunohistochemical staining and scoring for Ki-67 has not been demonstrated. Implications The addition of Ki-67 labeling index to prediction models incorporating standard pathological features, such as stage, grade, and lymphovascular invasion, may improve identification of patients who are at increased risk for disease progression after radical cystectomy and thus may benefit from treatment with adjuvant multimodal therapy. From the Editors
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Manuscript received April 25, 2008; revised October 21, 2008; accepted November 14, 2008.
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J Natl Cancer Inst 2009 101: 69.