Molecular classification of nonurothelial histologic subtypes of bladder cancer

Molecular subtyping of bladder cancer facilitates the development of personalized treatments and predict responses based on disease biology. Classically, bladder cancers have been classified into basal and luminal molecular subtypes. However, recent advances in sequencing techniques have brought more detailed strata at both the genomic and transcriptional level. This has resulted in molecular classifications with greater intrinsic differences among both muscle invasive (MIBCs) and non-muscle invasive bladder cancers (NMIBCs) as well as those differentiating urothelial and nonurothelial tumors. Recently, various groups have developed new or updated existing bladder cancer molecular classification schema. This review summarizes recent progress in molecular classification of nonurothelial histologic subtypes of bladder cancer. These tumors are canonically aggressive with few treatment options other than upfront extirpative surgery and thus represent a key target for novel molecular technology that can accelerate treatment development and improve prognostication.