Abstract 4902: Positive Ki-67 expression in post neoadjuvant chemotherapy (NAC) radical cystectomy samples are associated with lack of tumor downstaging and shorter overall survival (OS) in patients with muscle invasive bladder cancer (MIBC)
Authors: Rubino Selene , Kim Youngchul , Zhou Junmin , Peyton Charles , Gilbert Scott , Sexton Wade , Zhang Jingsong 
Published: August 2019

Abstract
Background: We recently reported single institution data on tumor downstaging and survival outcomes of 332 patients who underwent platinum based NAC followed by radical cystectomy for MIBC [Peyton et al. JAMA Oncol. 2018]. High expression levels of cell proliferation marker Ki-67 are associated with poor outcomes in chemotherapy naïve bladder cancer. Androgen receptor (AR) expression is associated with resistance to cisplatin in bladder cancer cell line models. We therefore studied Ki-67 and AR expression in our cohort of post NAC radical cystectomy samples and correlated them with tumor downstaging and OS.
Methods: Tissue microarrays (TMAs) were constructed from 130 post-NAC cystectomy samples and up to 5 cores were taken from each radical cystectomy sample. Matched lymph node metastases if present were included in TMAs. The expression of Ki-67 and AR were evaluated with immunohistochemistry and the average of the H score was used to represent each radical cystectomy sample and its matched lymph node metastasis.
Results: The median survival of this cohort of 130 patients was 33.4 months (range: 1.13 -127 months). 40 patients (31%) had tumor downstaging and 21 patients (16%) achieved pathological complete response. Using a Cox regression model for OS, positive Ki-67 expression in post NAC radical cystectomy samples is associated with poorer overall survival (hazard ratio=2.412, 95% CI:1.076-5.408, p=0.033), independent of the pathological N stage. Positive Ki-67 was significantly associated with lack of tumor downstage in a multivariable logistic regression model (odds ratio=0.081, 95% CI:0.014-0.464, p=0.004) while adjusting for adjuvant chemotherapy and pathological complete response. No statistically significant associations between AR and OS or AR and tumor downstaging were observed in multivariable analysis. When AR expression is evaluated as a binary variable (AR+, AR-), post NAC AR- expression is significantly associated with tumor downstaging compared to post NAC AR+ samples (Fisher’s exact test, p=0.002). When stratified by sex, a trend towards better survival was observed in females (36 patients) compared to males (94 patients) (p=0.089). Post NAC AR- female patients also demonstrated a trend toward better survival (Log rank test, p=0.497) when compared to post NAC AR+ females.
Conclusions: Positive Ki-67 expression in post NAC radical cystectomy sample is associated with poorer OS and lack of tumor downstaging. If confirmed by a larger data set, Ki-67 can serve as a biomarker to select MIBC patients for post cystectomy adjuvant therapy.
Note: This abstract was not presented at the meeting.
Citation Format: Selene Rubino, Youngchul Kim, Junmin Zhou, Charles Peyton, Scott Gilbert, Wade Sexton, Jingsong Zhang. Positive Ki-67 expression in post neoadjuvant chemotherapy (NAC) radical cystectomy samples are associated with lack of tumor downstaging and shorter overall survival (OS) in patients with muscle invasive bladder cancer (MIBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4902.