Johnson Iii Burles A, Teply Benjamin A, Kagemann Catherine, McGuire Bridget, Lombardo Kara, Jing Yuezhou, Langbo William, Epstein Jonathan I, Netto George J, Baras Alex S, Matoso Andres, McConkey David J, Gupta Amol, Ahuja Nita, Ross Ashley E, Pierorazio Phillip M, Comperat Eva, Hoffman-Censits Jean, Singla Nirmish, Patel Sunil H, Kates Max, Choi Woonyoung, Bivalacqua Trinity J, Hahn Noah M
Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
Bladder Cancer. 2024 Jun 18;10(2):133-143. doi: 10.3233/BLC-240008. eCollection 2024.
Sarcomatoid urothelial cancer of the bladder (SBC) is a rare, but aggressive histological subtype for which novel treatments are needed.
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.
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.
Sixteen patients with SBC received neoadjuvant CGD with a ypCR rate of 38% and < 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 ( (PD-L1)), chemokine (), and T-cell () genes.
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.
膀胱肉瘤样尿路上皮癌（SBC）是一种罕见但侵袭性强的组织学亚型，需要新的治疗方法。
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SBC肿瘤生物学特性。
对接受新辅助CGD治疗并进行分子分析的肌肉浸润性SBC患者进行单机构回顾性分析。患者每3周在第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，第9天皮下注射聚乙二醇化重组人粒细胞刺激因子6mg，共4个周期，随后进行膀胱切除术。主要终点是病理完全缓解（ypCR）率。
16例SBC患者接受了新辅助CGD治疗，ypCR率为38%，<ypT2率为50%。80%和40%的患者发生3级和4级毒性，但81%的患者能够完成>3个CGD周期，毒性可控。全转录组RNA测序显示SBC与传统尿路上皮肿瘤共聚类。SBC肿瘤的特征是具有基底-鳞状和富含基质的基因特征，免疫检查点（PD-L1）、趋化因子和T细胞基因的表达经常增加。
SBC是一种对化疗敏感的亚型，新辅助CGD治疗后的ypCR率与膀胱尿路上皮癌相似。全转录组组织分析显示免疫检查点和T细胞基因表达增加，具有治疗意义。
