Genetic Differences Between Bladder and Upper Urinary Tract Carcinoma: Implications for Therapy.

Bladder urothelial carcinoma (BUC) and upper tract urothelial carcinoma (UTUC) have genetic differences, which may influence therapy.

The aim of the current review was to summarize the current genetic understanding of upper tract and BUC.

PubMed, Cochrane, and Web of Science online databases were searched systematically up to February 2020, using the following keywords: urothelial carcinomas, upper urinary tract, renal pelvis, ureter, bladder cancer, and genetics.

UTUC and BUC share mutations in similar genes, such as FGFR3, TP53, and HRAS, and epigenetic genes, such as KDM6A and KMT2A-C, but at varying frequencies. Furthermore, subtyping of UTUC and BUC has identified similar expression subtypes, but UTUC is more often luminal with more T-cell depletion. Clonal studies indicate that BUC after UTUC is also likely luminal, while UTUC after BUC is often basal.

UTUC and BUC share many genomic alterations, but at different frequencies, which recapitulate with their metachronous recurrences. These differences likely contribute to the behavior of these two cancers and imply that they and their metachronous recurrences should be treated as two related yet distinct entities.

Urothelial carcinoma of the bladder has distinct genomic features, which are different from distinct genomic features of urothelial carcinoma of the renal pelvis and/or ureter. These features can be used for tailored treatment options specific to tumors of different locations.

European urology oncology. 2020 Dec 29 [Epub ahead of print]

John P Sfakianos, Zeynep Gul, Shahrokh F Shariat, Surena F Matin, Siamak Daneshmand, Elizabeth Plimack, Seth Lerner, Morgan Roupret, Sumanta Pal

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: ., Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Department of Urology, Comprehensive Cancer Center, Medical University Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Department of Urology, University of Texas Southwestern, Dallas, TX, USA., Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Institute of Urology and USC Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA., Fox Chase Cancer Center, Philadelphia, PA, USA., Scott Department of Urology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA., Urology Department, GRC n°5, Predictive Onco-Uro, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France., Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.