Role of B7‐H3 in predicting response to neoadjuvant chemotherapy in muscle‐invasive bladder cancer

Abstract Background Neoadjuvant platinum‐based chemotherapy offers a modest survival advantage in muscle‐invasive bladder cancer (MIBC) for patients with pathologic response. B7‐H3 (CD276), an immune checkpoint overexpressed in various cancers, including urothelial‐cell carcinoma (UCC), has been ass...

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Main Authors: Ekamjit S. Deol, Reza Nabavizadeh, Roxane R. Lavoie, Mihai G. Dumbrava, Edlira Horjeti, Prabin Thapa, John C. Cheville, Igor Frank, Fabrice Lucien
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Language:English
Published: Wiley 2024-11-01
Series:BJUI Compass
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Online Access:https://doi.org/10.1002/bco2.418
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author Ekamjit S. Deol
Reza Nabavizadeh
Roxane R. Lavoie
Mihai G. Dumbrava
Edlira Horjeti
Prabin Thapa
John C. Cheville
Igor Frank
Fabrice Lucien
author_facet Ekamjit S. Deol
Reza Nabavizadeh
Roxane R. Lavoie
Mihai G. Dumbrava
Edlira Horjeti
Prabin Thapa
John C. Cheville
Igor Frank
Fabrice Lucien
author_sort Ekamjit S. Deol
collection DOAJ
description Abstract Background Neoadjuvant platinum‐based chemotherapy offers a modest survival advantage in muscle‐invasive bladder cancer (MIBC) for patients with pathologic response. B7‐H3 (CD276), an immune checkpoint overexpressed in various cancers, including urothelial‐cell carcinoma (UCC), has been associated with chemoresistance and poor oncologic outcomes. We aimed to explore if B7H3 expression on bladder biopsy samples was a predictive biomarker for pathologic response to neoadjuvant platinum‐based chemotherapy. Methods This was a retrospective cohort study among MIBC patients receiving neoadjuvant platinum‐based chemotherapy followed by radical cystectomy. All patients underwent routine preoperative biopsy of their tumour. Immunohistochemistry was used to evaluate B7‐H3 expression from pre‐operative specimens. The primary outcome of interest was pathologic complete response (pCR). Statistical analysis included Mann–Whitney U test, Fisher's exact test, Kaplan–Meier method, and Cox regression for survival analysis. Results Among 87 patients analysed, high B7‐H3 expression was found in 44.8% (n = 39) of patients. The median follow‐up periods were similar between the high and low B7‐H3 groups (high expression; 4.29 years [SD 3.04], low expression 3.94 years [SD 3.04], p = 0.60). Only 20.5% of patients with high B7‐H3 expression achieved pCR, compared to 41.7% in the low expression group (p = 0.04). Cox regression showed no significant differences in recurrence‐free or cancer‐specific survival between the high and low B7‐H3 expression groups (p > 0.05). Conclusion High B7‐H3 expression is associated with a reduced likelihood of achieving pCR in MIBC patients undergoing neoadjuvant chemotherapy. This suggests B7‐H3's potential as a predictive biomarker for chemotherapy response. Further research is needed to explore the role of B7‐H3 on platinum‐based chemotherapy response in urothelial cancer.
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spelling doaj-art-d310f57a069149ad9605a1c2f4abd6e22025-01-22T02:21:03ZengWileyBJUI Compass2688-45262024-11-015111166117210.1002/bco2.418Role of B7‐H3 in predicting response to neoadjuvant chemotherapy in muscle‐invasive bladder cancerEkamjit S. Deol0Reza Nabavizadeh1Roxane R. Lavoie2Mihai G. Dumbrava3Edlira Horjeti4Prabin Thapa5John C. Cheville6Igor Frank7Fabrice Lucien8Department of Urology Mayo Clinic Rochester Minnesota USADepartment of Urology Mayo Clinic Rochester Minnesota USADepartment of Urology Mayo Clinic Rochester Minnesota USADivision of Experimental Pathology Mayo Clinic Rochester MNDepartment of Urology Mayo Clinic Rochester Minnesota USADepartment of Urology Mayo Clinic Rochester Minnesota USADivision of Experimental Pathology Mayo Clinic Rochester MNDepartment of Urology Mayo Clinic Rochester Minnesota USADepartment of Urology Mayo Clinic Rochester Minnesota USAAbstract Background Neoadjuvant platinum‐based chemotherapy offers a modest survival advantage in muscle‐invasive bladder cancer (MIBC) for patients with pathologic response. B7‐H3 (CD276), an immune checkpoint overexpressed in various cancers, including urothelial‐cell carcinoma (UCC), has been associated with chemoresistance and poor oncologic outcomes. We aimed to explore if B7H3 expression on bladder biopsy samples was a predictive biomarker for pathologic response to neoadjuvant platinum‐based chemotherapy. Methods This was a retrospective cohort study among MIBC patients receiving neoadjuvant platinum‐based chemotherapy followed by radical cystectomy. All patients underwent routine preoperative biopsy of their tumour. Immunohistochemistry was used to evaluate B7‐H3 expression from pre‐operative specimens. The primary outcome of interest was pathologic complete response (pCR). Statistical analysis included Mann–Whitney U test, Fisher's exact test, Kaplan–Meier method, and Cox regression for survival analysis. Results Among 87 patients analysed, high B7‐H3 expression was found in 44.8% (n = 39) of patients. The median follow‐up periods were similar between the high and low B7‐H3 groups (high expression; 4.29 years [SD 3.04], low expression 3.94 years [SD 3.04], p = 0.60). Only 20.5% of patients with high B7‐H3 expression achieved pCR, compared to 41.7% in the low expression group (p = 0.04). Cox regression showed no significant differences in recurrence‐free or cancer‐specific survival between the high and low B7‐H3 expression groups (p > 0.05). Conclusion High B7‐H3 expression is associated with a reduced likelihood of achieving pCR in MIBC patients undergoing neoadjuvant chemotherapy. This suggests B7‐H3's potential as a predictive biomarker for chemotherapy response. Further research is needed to explore the role of B7‐H3 on platinum‐based chemotherapy response in urothelial cancer.https://doi.org/10.1002/bco2.418biomarkersbladder cancercystectomyneoadjuvant chemotherapy
spellingShingle Ekamjit S. Deol
Reza Nabavizadeh
Roxane R. Lavoie
Mihai G. Dumbrava
Edlira Horjeti
Prabin Thapa
John C. Cheville
Igor Frank
Fabrice Lucien
Role of B7‐H3 in predicting response to neoadjuvant chemotherapy in muscle‐invasive bladder cancer
BJUI Compass
biomarkers
bladder cancer
cystectomy
neoadjuvant chemotherapy
title Role of B7‐H3 in predicting response to neoadjuvant chemotherapy in muscle‐invasive bladder cancer
title_full Role of B7‐H3 in predicting response to neoadjuvant chemotherapy in muscle‐invasive bladder cancer
title_fullStr Role of B7‐H3 in predicting response to neoadjuvant chemotherapy in muscle‐invasive bladder cancer
title_full_unstemmed Role of B7‐H3 in predicting response to neoadjuvant chemotherapy in muscle‐invasive bladder cancer
title_short Role of B7‐H3 in predicting response to neoadjuvant chemotherapy in muscle‐invasive bladder cancer
title_sort role of b7 h3 in predicting response to neoadjuvant chemotherapy in muscle invasive bladder cancer
topic biomarkers
bladder cancer
cystectomy
neoadjuvant chemotherapy
url https://doi.org/10.1002/bco2.418
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