The Many Faces of Urothelial Carcinomas: An Update From Pathology to Clinical Approach and Challenges in Practice

Urothelial carcinoma is a heterogeneous disease with histomorphological and genomic variations throughout the same tumor or between tumors from different patients. It has been shown that most of these histologic and genetic differences have prognostic significance and may have a guiding role in determining the appropriate treatment choice for the patient. Therefore, it is crucial for both the pathologist and the clinician to be conscious of these variations and to consider them in patient management. Recently, a consensus molecular classification has been developed and categorized urothelial carcinomas into 6 subclasses. These molecular subclasses seem to be associated with prognosis and/or response to certain therapeutic approaches like chemotherapy or immune checkpoint inhibitory therapy; however, it has not yet been sufficiently validated and has some limitations for routine application. As is well known, there are therapeutic limitations in locally advanced or metastatic urothelial carcinomas, especially those inappropriate for standard therapy with platinum-based chemotherapy regimens. Emerging new therapeutic approaches and testing for appropriate patient selection for those are discussed in this article.