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Updated: May 5, 2026
An Orthotopic Bladder Tumor Model and the Evaluation of Intravesical saRNA Treatment
Published on: July 28, 2012
Neoadjuvant Cisplatin, Gemcitabine, and Docetaxel in Sarcomatoid Bladder Cancer: Clinical Activity and Whole
Burles A Johnson Iii1,2, Benjamin A Teply1,3, Catherine Kagemann1,2
1Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
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.
