TY - JOUR
T1 - Multi-institutional validation of the predictive value of Ki-67 in patients with high grade urothelial carcinoma of the upper urinary tract
AU - Krabbe, Laura Maria
AU - Bagrodia, Aditya
AU - Haddad, Ahmed Q.
AU - Kapur, Payal
AU - Khalil, Dina
AU - Hynan, Linda S.
AU - Wood, Christopher G.
AU - Karam, Jose A.
AU - Weizer, Alon Z.
AU - Raman, Jay D.
AU - Remzi, Mesut
AU - Rioux-Leclercq, Nathalie
AU - Haitel, Andrea
AU - Roscigno, Marco
AU - Bolenz, Christian
AU - Bensalah, Karim
AU - Sagalowsky, Arthur I.
AU - Shariat, Shahrokh F.
AU - Lotan, Yair
AU - Margulis, Vitaly
N1 - Publisher Copyright:
© 2015 American Urological Association Education and Research, Inc.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - Purpose We validate the independent predictive value of Ki-67 in patients with high grade upper tract urothelial carcinoma. Materials and Methods A total of 475 patients from the international Upper Tract Urothelial Carcinoma Collaboration who underwent extirpative surgery for high grade upper tract urothelial carcinoma were included in this study. Immunohistochemical staining for Ki-67 was performed on tissue microarray formed from this patient cohort. Ki-67 expression was assessed in a semiquantitative fashion and considered over expressed at a cutoff of 20%. Multivariate analyses were performed to assess independent predictors of oncologic outcomes and Harrell's C indices were calculated for predictive models. Results The median age of the cohort was 69.7 years and 55.2% of patients were male. Ki-67 was over expressed in 25.9% of patients. Ki-67 over expression was significantly associated with ureteral tumor location, higher pT-stage, lymphovascular invasion, sessile tumor architecture, tumor necrosis, concomitant carcinoma in situ and regional lymph node metastases. On Kaplan-Meier analyses over expressed Ki-67 was associated with worse recurrence-free survival (HR 12.6, p <0.001) and cancer specific survival (HR 15.8, p <0.001). On multivariate analysis Ki-67 was an independent predictor of recurrence-free survival (HR 1.6, 95% CI 1.07-2.30, p=0.021) and cancer specific survival (HR 1.9, 95% CI 1.29-2.90, p=0.001). Ki-67 improved Harrell's C index from 0.66 to 0.70 (p <0.0001) for recurrence-free survival as well as cancer specific survival in our preoperative model, and from 0.81 to 0.82 (p=0.0018) for recurrence-free survival and 0.81 to 0.83 (p=0.005) for cancer specific survival in our postoperative model. Conclusions Ki-67 was validated as an independent predictor of recurrence-free survival and cancer specific survival in patients treated with extirpative surgery for high grade upper tract urothelial carcinoma in a large, multi-institutional cohort.
AB - Purpose We validate the independent predictive value of Ki-67 in patients with high grade upper tract urothelial carcinoma. Materials and Methods A total of 475 patients from the international Upper Tract Urothelial Carcinoma Collaboration who underwent extirpative surgery for high grade upper tract urothelial carcinoma were included in this study. Immunohistochemical staining for Ki-67 was performed on tissue microarray formed from this patient cohort. Ki-67 expression was assessed in a semiquantitative fashion and considered over expressed at a cutoff of 20%. Multivariate analyses were performed to assess independent predictors of oncologic outcomes and Harrell's C indices were calculated for predictive models. Results The median age of the cohort was 69.7 years and 55.2% of patients were male. Ki-67 was over expressed in 25.9% of patients. Ki-67 over expression was significantly associated with ureteral tumor location, higher pT-stage, lymphovascular invasion, sessile tumor architecture, tumor necrosis, concomitant carcinoma in situ and regional lymph node metastases. On Kaplan-Meier analyses over expressed Ki-67 was associated with worse recurrence-free survival (HR 12.6, p <0.001) and cancer specific survival (HR 15.8, p <0.001). On multivariate analysis Ki-67 was an independent predictor of recurrence-free survival (HR 1.6, 95% CI 1.07-2.30, p=0.021) and cancer specific survival (HR 1.9, 95% CI 1.29-2.90, p=0.001). Ki-67 improved Harrell's C index from 0.66 to 0.70 (p <0.0001) for recurrence-free survival as well as cancer specific survival in our preoperative model, and from 0.81 to 0.82 (p=0.0018) for recurrence-free survival and 0.81 to 0.83 (p=0.005) for cancer specific survival in our postoperative model. Conclusions Ki-67 was validated as an independent predictor of recurrence-free survival and cancer specific survival in patients treated with extirpative surgery for high grade upper tract urothelial carcinoma in a large, multi-institutional cohort.
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U2 - 10.1016/j.juro.2014.11.007
DO - 10.1016/j.juro.2014.11.007
M3 - Article
C2 - 25451830
AN - SCOPUS:84927913510
SN - 0022-5347
VL - 193
SP - 1486
EP - 1493
JO - Journal of Urology
JF - Journal of Urology
IS - 5
ER -
