Multicenter phase 2 trial of neoadjuvant tislelizumab plus gemcitabine-cisplatin chemotherapy for resectable muscle-invasive bladder cancer

PD-1 blockade with tislelizumab has been approved for metastatic urothelial carcinoma but not as part of neoadjuvant therapy for resectable muscle-invasive bladder cancer (MIBC). A multicenter phase 2 trial in China included 65 patients with cT2-4aN0M0 MIBC who received neoadjuvant tislelizumab plus gemcitabine-cisplatin chemotherapy; 57 of them underwent radical cystectomy. The primary endpoint of pathologic complete response rate was 50.9% (95% CI 37.3-64.4%) and the pathologic downstaging rate was 75.4% (62.2-85.9%). Genomic and transcriptomic analyses revealed three MIBC molecular subtypes: S1 (immune desert; n=19) with activated cell-cycle pathway, S2 (immune-excluded; n=13) with activated transforming growth factor-β pathway, and S3 (immune-inflamed; n=15) with upregulated interferon-α and interferon-γ response. Post hoc analysis showed pCR rates of 16%, 77%, and 80% in S1, S2, and S3, respectively. The authors conclude that neoadjuvant tislelizumab plus gemcitabine-cisplatin for resectable MIBC produced high pCR rates in selected patients.