Molecular Subtypes of Muscle-Invasive Bladder Cancer

An important tool for understanding the biology of muscle-invasive bladder cancer (MIBC) is molecular subtype classification. Molecular subtypes are qualitatively distinct biological entities that can be identified by molecular analysis of tumor tissue. This chapter describes how such entities have been discovered and described for MIBC and gives an overview of the characteristics that the luminal, basal/squamous, neuroendocrine-like, and other tumor categories possess. Special attention is given to the MIBC Consensus subtypes since they represent a joint effort by all researchers in the field to define a common reference against which all other classification systems can be compared. In addition to outlining the history of MIBC subtype discovery, this chapter also attempts to inform the reader of some understudied aspects of subtype classification. Examples of such aspects include discussion of whether there is a need for further MIBC subtype discovery, to what extent intra-tumor heterogeneity affects classification, and what the advantages of IHC- versus RNA-based classification are. The chapter comes to the following conclusions: (a) Although there is room for minor modifications, subtype discovery in MIBC is largely completed, (b) Testing the clinical utility of MIBC subtyping is an area of intense ongoing work, (c) The causal origins of the molecular subtypes have not been sufficiently studied and remain largely unknown.