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 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.
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.
Bladder cancer (Amsterdam, Netherlands). 2024 Jun 18*** epublish ***
Burles A Johnson Iii, Benjamin A Teply, Catherine Kagemann, Bridget McGuire, Kara Lombardo, Yuezhou Jing, William Langbo, Jonathan I Epstein, George J Netto, Alex S Baras, Andres Matoso, David J McConkey, Amol Gupta, Nita Ahuja, Ashley E Ross, Phillip M Pierorazio, Eva Comperat, Jean Hoffman-Censits, Nirmish Singla, Sunil H Patel, Max Kates, Woonyoung Choi, Trinity J Bivalacqua, Noah M Hahn
Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA., The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA., The James Buchanan Brady Urological Institute, Baltimore, MD, USA., Department of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Department of Surgery, Johns Hopkins University, Division of Surgical Oncology, Baltimore, MD, USA., Department of Pathology, Medical University of Vienna, Vienna, Austria.