Molecular Subtypes of Non-Muscle-Invasive Bladder Cancer

Non-muscle-invasive bladder cancers (NMIBCs) show large variation in disease aggressiveness and treatment response which is not fully explained by differences in clinical and pathological factors. Researchers have therefore studied different molecular layers of tumors, mainly gene expression profiling, to unravel underlying molecular subtypes that can explain this phenotypic variation. In addition, molecular subtypes can potentially be used for risk stratification of patients and prediction of treatment response based on the biological tumor features. NMIBC subtypes have been investigated in combination with muscle-invasive bladder cancers (MIBCs), using NMIBCs only and separated by tumor stage. Molecularly high-risk tumors across schemes are generally characterized by pronounced cell cycle activity, frequent TP53 alterations and a high degree of genomic instability. In this chapter, we describe the different NMIBC subtype classification schemes reported. Finally, we discuss the clinical utility of molecular subtypes and what still needs to be answered before clinical implementation.