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

Background: Neoadjuvant platinum-based chemotherapy offers a modest survivaladvantage in muscle-invasive bladder cancer (MIBC) for patients with pathologicresponse. B7-H3 (CD276), an immune checkpoint overexpressed in various cancers,including urothelial-cell carcinoma (UCC), has been associated with chemoresistanceand poor oncologic outcomes. We aimed to explore if B7H3 expression on bladderbiopsy samples was a predictive biomarker for pathologic response to neoadjuvantplatinum-based chemotherapy. Methods: This was a retrospective cohort study among MIBC patients receivingneoadjuvant platinum-based chemotherapy followed by radical cystectomy. Allpatients underwent routine preoperative biopsy of their tumour. Immunohistochem-istry was used to evaluate B7-H3 expression from pre-operative specimens. The pri-mary outcome of interest was pathologic complete response (pCR). Statisticalanalysis included Mann-WhitneyUtest, 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 highand low B7-H3 groups (high expression; 4.29 years [SD 3.04], low expression3.94 years [SD 3.04],p=0.60). Only 20.5% of patients with high B7-H3 expressionachieved pCR, compared to 41.7% in the low expression group (p=0.04). Coxregression showed no significant differences in recurrence-free or cancer-specificsurvival between the high and low B7-H3 expression groups (p> 0.05). Conclusion: High B7-H3 expression is associated with a reduced likelihood of achiev-ing pCR in MIBC patients undergoing neoadjuvant chemotherapy. This suggestsB7-H3's potential as a predictive biomarker for chemotherapy response. Furtherresearch is needed to explore the role of B7-H3 on platinum-based chemotherapyresponse in urothelial cancer.