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Neoadjuvant Cisplatin, Gemcitabine, and Docetaxel in Sarcomatoid Bladder Cancer: Clinical Activity and Whole Transcriptome Analysis.
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.
Afiliação
  • Johnson Iii BA; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
  • Teply BA; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
  • Kagemann C; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
  • McGuire B; University of Nebraska Fred and Pamela Buffett Cancer Center, Omaha, NE, USA.
  • Lombardo K; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
  • Jing Y; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
  • Langbo W; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
  • Epstein JI; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
  • Netto GJ; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
  • Baras AS; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Matoso A; The James Buchanan Brady Urological Institute, Baltimore, MD, USA.
  • McConkey DJ; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
  • Gupta A; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
  • Ahuja N; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
  • Ross AE; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Pierorazio PM; Department of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Comperat E; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
  • Hoffman-Censits J; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Singla N; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
  • Patel SH; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
  • Kates M; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Choi W; The James Buchanan Brady Urological Institute, Baltimore, MD, USA.
  • Bivalacqua TJ; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
  • Hahn NM; The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
Bladder Cancer ; 10(2): 133-143, 2024.
Article em En | MEDLINE | ID: mdl-39131872
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Bladder Cancer Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Bladder Cancer Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Holanda