Collaborative study from the Bladder Cancer Advocacy Network for the genomic analysis of metastatic urothelial cancer.

Urothelial Cancer - Genomic Analysis to Improve Patient Outcomes and Research (NCT02643043), UC-GENOME, is a genomic analysis and biospecimen repository study in 218 patients with metastatic urothelial carcinoma.

Here we report on the primary outcome of the UC-GENOME-the proportion of subjects who received next generation sequencing (NGS) with treatment options-and present the initial genomic analyses and clinical correlates. 69.3% of subjects had potential treatment options, however only 5.0% received therapy based on NGS. We found an increased frequency of TP53E285K mutations as compared to non-metastatic cohorts and identified features associated with benefit to chemotherapy and immune checkpoint inhibition, including: Ba/Sq and Stroma-rich subtypes, APOBEC mutational signature (SBS13), and inflamed tumor immune phenotype. Finally, we derive a computational model incorporating both genomic and clinical features predictive of immune checkpoint inhibitor response. Future work will utilize the biospecimens alongside these foundational analyses toward a better understanding of urothelial carcinoma biology.

Nature communications. 2022 Nov 04*** epublish ***

Jeffrey S Damrauer, Wolfgang Beckabir, Jeff Klomp, Mi Zhou, Elizabeth R Plimack, Matthew D Galsky, Petros Grivas, Noah M Hahn, Peter H O'Donnell, Gopa Iyer, David I Quinn, Benjamin G Vincent, Diane Zipursky Quale, Sara E Wobker, Katherine A Hoadley, William Y Kim, Matthew I Milowsky

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA., Department of Hematology and Oncology, Fox Chase Cancer Center, Temple Health, Philadelphia, PA, USA., Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, USA., Johns Hopkins University School of Medicine, Baltimore, MD, USA., Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA., Memorial Sloan Kettering Cancer Center, New York, NY, USA., University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA., Bladder Cancer Advocacy Network, Bethesda, MD, USA., Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA. ., Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA. .

Read an Expert Commentary by Bishoy Faltas, MD

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