Abstract
Bladder cancer is a heterogeneous disease that is not depicted by current classification systems. It was originally classified into non-muscle invasive and muscle invasive. However, clinically and genetically variable tumors are summarized within both classes. A definition of three groups may better account for the divergence in prognosis and probably also choice of treatment. The first group represents mostly non-invasive tumors that reoccur but do not progress. Contrarily, the second group represent non-muscle invasive tumors that likely progress to the third group, the muscle invasive tumors. High throughput tumor profiling improved our understanding of the biology of bladder cancer. It allows the identification of molecular subtypes, at least three for non-muscle invasive bladder cancer (Class I, Class II and Class III) and six for muscle-invasive bladder cancer (luminal papillary, luminal non-specified, luminal unstable, stroma-rich, basal/squamous and neuroendocrine-like) with distinct clinical and molecular phenotypes. Molecular subtypes can be potentially used to predict the response to treatment (e.g., neoadjuvant chemotherapy and immune checkpoint inhibitors). Moreover, they may allow to characterize the evolution of bladder cancer through different pathways. However, to move towards precision medicine, the understanding of the biological meaning of these molecular subtypes and differences in the composition of cell subpopulations will be mandatory.
Highlights
IntroductionBladder cancer (BLCa) is one of the most common cancers of the genitourinary tract. It is the tenth most common cancer worldwide, accounting for 549,000 new cases and about 200,000 deaths per year [1]
The Clinical Problem of Bladder CancerBladder cancer (BLCa) is one of the most common cancers of the genitourinary tract
Physicians are often met with treatment failure and/or reoccurrence in all Bladder CancerBladder cancer (BLCa) groups, indicating that the management of BLCa is complex and current classification systems do not depict the heterogeneity of this disease
Summary
Bladder cancer (BLCa) is one of the most common cancers of the genitourinary tract. It is the tenth most common cancer worldwide, accounting for 549,000 new cases and about 200,000 deaths per year [1]. The first group consists of NMIBC confined to the mucosa [14] This group is divided into high- and low-grade pTa depending on cellular atypia and alterations in tumor architecture. The second group consists of NMIBC tumors that invade the submucosal layer, the lamina propria These include stage pT1 and are of high-grade in most of the cases. MIBC tumors are staged from T2a to T4b depending on the extent of muscle invasion and are of high-grade in the majority of the cases. Huge efforts are undertaken to understand the biology of BLCa. Tumor profiling on large-scale cohorts has dramatically improved our understanding of the biology of this disease and may allow us to identify molecular subtypes with a distinct clinical and molecular phenotype. We will discuss how molecular subtypes discovered from the profiling of tumor samples improved our understanding of BLCa and their potential clinical meaning and application
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