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

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.