In the last few years, significant progress has been achieved in the therapeutic options for advanced urothelial bladder cancer.
The aim of this work was to give an overview of the status and future perspective of the therapeutic options in this setting.
Its focus is on the discussion of tissue-based therapy-predictive markers, which are evaluated through (molecular) pathology and thereby strengthening the role of pathology itself.
Current (clinical study) data, the literature, and our own expertise were considered and summarized in the areas of therapy prediction of platinum-based chemotherapy, immunotherapy, and other therapeutic approaches.
Molecular subtypes exhibit a predictive value both in platinum-based chemotherapy as well as in immunotherapy. However, further work is required to elucidate the predictive role of molecular subtypes in both settings. Changes in the DNA damage repair enzyme (DDR) genes, ERCC2, and ERBB2 as well as differences in the expression of EMMPRIN, survivin, and HMGA2 show promising results as further markers of chemotherapy efficacy. In the prediction of immunotherapy success, this mainly relates to the evaluation of the tumor mutation burden (TMB), tumor neoantigen burden (TNB), APOBEC signatures (MSig1; 3A/3B), and CD8-positive T‑effector cell signature. When using the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib, which has not yet been approved in Germany, the evaluation of specific FGFR mutations and/or gene fusions by a companion diagnostic test is mandatory in the USA.
Der Pathologe. 2019 Nov 08 [Epub ahead of print]
H Reis, T Szarvas
Institut für Pathologie, Westdeutsches Tumorzentrum, Universitätsmedizin Essen, Universität Duisburg-Essen, Essen, Deutschland. ., Klinik für Urologie, Semmelweis Universität, Budapest, Ungarn.