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Abstract：
BACKGROUND: Sarcomatoid urothelial cancer of the bladder (SBC) is a rare, but aggressive histological subtype for which novel treatments are needed.
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.
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.
摘要：
背景：膀胱肉瘤样尿路上皮癌（SBC）是一种罕见的，而是需要新治疗的侵袭性组织学亚型。
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%，3个CGD周期时是可控的.全转录组RNA测序表明SBC与常规尿路上皮肿瘤的共聚集。SBC肿瘤的特征是基底鳞状和基质丰富的基因特征，免疫检查点（CD274（PD-L1））的表达频繁增加，趋化因子（CXCL9），和T细胞（CD8A）基因。
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。
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。
