Pathogenic activating mutations in the fibroblast growth factor receptor 3 (FGFR3) drive disease maintenance and progression in urothelial cancer. 10-15% of muscle-invasive and metastatic urothelial cancer (MIBC/mUC) are FGFR3-mutant. Selective targeting of FGFR3 hotspot mutations with tyrosine kinase inhibitors (e.g., erdafitinib) is approved for mUC and requires FGFR3 mutational testing. However, current testing assays (polymerase chain reaction or next-generation sequencing) necessitate high tissue quality, have long turnover time, and are expensive. To overcome these limitations, we develop a deep-learning model that detects FGFR3 mutations using routine hematoxylin-eosin slides. Encompassing 1222 cases, our study is a large-scale validation of a model prescreening FGFR3 mutations for MIBC and mUC patients. In this work, we demonstrate that our model achieves high sensitivity (>93%) on advanced and metastatic cases while reducing molecular testing by 40% on average, thereby offering a cost-effective and rapid pre-screening tool for identifying patients eligible for FGFR3 targeted therapies.
Nature communications. 2024 Dec 30*** epublish ***
Pierre-Antoine Bannier, Charlie Saillard, Philipp Mann, Maxime Touzot, Charles Maussion, Christian Matek, Niklas Klümper, Johannes Breyer, Ralph Wirtz, Danijel Sikic, Bernd Schmitz-Dräger, Bernd Wullich, Arndt Hartmann, Sebastian Försch, Markus Eckstein
Owkin, Paris, France. ., Owkin, Paris, France., Institute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany., Department of Urology, St. Caritas Hospital Regensburg, University of Regensburg, Regensburg, Germany., STRATIFYER Molecular Pathology, Cologne, Germany., Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) and Comprehensive Cancer Center Alliance WERA (CCC WERA), Erlangen, Germany., Urologie 24, St. Theresienkrankenhaus, Nürnberg, Germany., Institute of Pathology, University Medical Center Mainz, Johannes Gutenberg-Universität Mainz, Mainz, Germany., Institute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. .