Selene Rubino1, Youngchul Kim2, Junmin Zhou2, Jasreman Dhilon3, Roger Li4, Philippe Spiess4, Michael Poch4, Brandon J Manley4, Julio Pow-Sang4, Scott Gilbert4, Wade Sexton4, Jingsong Zhang5. 1. Morsani College of Medicine, University of South Florida, Tampa, FL, USA. 2. Department of Biostatistics and Bioinformatics, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. 3. Department of Pathology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. 4. Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, WCB-GU, Tampa, FL, 33612, USA. 5. Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, WCB-GU, Tampa, FL, 33612, USA. Jingsong.zhang@moffitt.org.
Abstract
PURPOSE: There is an unmet need to develop prognostic biomarkers in post-neoadjuvant chemotherapy (NAC) muscle-invasive bladder cancer (MIBC) patients. We examine whether Ki-67 and PD-L1 expression can be used to guide adjuvant therapy. METHODS: Tissue microarrays were constructed from 130 post-NAC radical cystectomy samples. Up to 5 cores per sample were included. Expressions of Ki-67 and PD-L1 were evaluated using immunohistochemistry (IHC). RESULTS: Using a Cox regression model, positive Ki-67 expression in post-NAC radical cystectomy samples was associated with poorer overall survival (OS) (HR = 2.412, 95% CI, 1.076-5.408), independent of the pathological lymph node/N-stage. Positive Ki-67 expression was also associated with lack of tumor downstaging in a multivariable logistic regression model analysis (OR = 0.081, 95% CI, 0.014-0.464). PD-L1- and PD-L1+ expression was associated with a median OS of 49.8 months and 26.9 months, respectively, which did not reach statistical significance. Patients with Ki-67/PD-L1 double-negative tumors had a significantly longer median OS of 98.2 months versus 29.9 and 26.9 months in PD-L1-/Ki-67+ and PD-L1+/Ki-67+ tumors, respectively. Lack of tumor downstaging was significantly associated with positive Ki-67 and positive PD-L1 expression. CONCLUSION: Positive Ki-67 and PD-L1 expression in post-NAC radical cystectomy samples was associated with inferior OS and absence of tumor downstaging. IHC on Ki-67 and PD-L1 would help to select patients for adjuvant therapy in post-NAC muscle-invasive bladder cancer.
PURPOSE: There is an unmet need to develop prognostic biomarkers in post-neoadjuvant chemotherapy (NAC) muscle-invasive bladder cancer (MIBC) patients. We examine whether Ki-67 and PD-L1 expression can be used to guide adjuvant therapy. METHODS: Tissue microarrays were constructed from 130 post-NAC radical cystectomy samples. Up to 5 cores per sample were included. Expressions of Ki-67 and PD-L1 were evaluated using immunohistochemistry (IHC). RESULTS: Using a Cox regression model, positive Ki-67 expression in post-NAC radical cystectomy samples was associated with poorer overall survival (OS) (HR = 2.412, 95% CI, 1.076-5.408), independent of the pathological lymph node/N-stage. Positive Ki-67 expression was also associated with lack of tumor downstaging in a multivariable logistic regression model analysis (OR = 0.081, 95% CI, 0.014-0.464). PD-L1- and PD-L1+ expression was associated with a median OS of 49.8 months and 26.9 months, respectively, which did not reach statistical significance. Patients with Ki-67/PD-L1 double-negative tumors had a significantly longer median OS of 98.2 months versus 29.9 and 26.9 months in PD-L1-/Ki-67+ and PD-L1+/Ki-67+ tumors, respectively. Lack of tumor downstaging was significantly associated with positive Ki-67 and positive PD-L1 expression. CONCLUSION: Positive Ki-67 and PD-L1 expression in post-NAC radical cystectomy samples was associated with inferior OS and absence of tumor downstaging. IHC on Ki-67 and PD-L1 would help to select patients for adjuvant therapy in post-NACmuscle-invasive bladder cancer.
Entities:
Keywords:
Ki-67; Muscle-invasive bladder cancer neoadjuvant chemotherapy; PD-L1
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