OBJECTIVE: We evaluated the clinical activity and safety of neoadjuvant cisplatin plus gemcitabine plus docetaxel (CGD) in muscle-invasive patients with SBC and assessed SBC tumor biology by whole transcriptome RNA sequencing.
METHODS: A single-institution, retrospective analysis of muscle-invasive SBC patients treated with neoadjuvant CGD with molecular analysis. Patients received cisplatin 35 mg/m2 + gemcitabine 800 mg/m2 + docetaxel 35 mg/m2 intravenously on days 1 and 8 + pegfilgrastim 6 mg subcutaneously on day 9 every 3 weeks for 4 cycles followed by cystectomy. The primary endpoint was pathologic complete response (ypCR) rate.
RESULTS: Sixteen patients with SBC received neoadjuvant CGD with a ypCR rate of 38% and a < ypT2 rate of 50%. Grade 3 and 4 toxicity occurred in 80% and 40% of patients, but was manageable with 81% of patients completing > 3 CGD cycles. Whole transcriptome RNA sequencing demonstrates co-clustering of SBC with conventional urothelial tumors. SBC tumors are characterized by basal-squamous and stroma rich gene signatures with frequent increased expression of immune checkpoint (CD274 (PD-L1)), chemokine (CXCL9), and T-cell (CD8A) genes.
CONCLUSIONS: SBC is a chemosensitive subtype, with ypCR rate similar to urothelial bladder cancer following CGD neoadjuvant therapy. Whole transcriptome tissue analyses demonstrate increased expression of immune checkpoint and T-cell genes with therapeutic implications.
目的:我们评估了新辅助顺铂联合吉西他滨联合多西他赛(CGD)在肌肉浸润性SBC患者中的临床活性和安全性,并通过全转录组RNA测序评估了SBC肿瘤生物学。
方法:单一机构,采用分子分析对新辅助CGD治疗的肌肉浸润性SBC患者进行回顾性分析。患者在第1天和第8天静脉注射顺铂35mg/m2吉西他滨800mg/m2多西他赛35mg/m2,每3周一次,第9天皮下注射pegfilgrastim6mg,共4个周期,然后进行膀胱切除术。主要终点是病理完全缓解(ypCR)率。
结果:16例SBC患者接受新辅助CGD,ypCR率为38%,
结论:SBC是一种化疗敏感亚型,CGD新辅助治疗后,ypCR率与膀胱尿路上皮癌相似。全转录组组织分析表明免疫检查点和T细胞基因的表达增加,具有治疗意义。