Histologic subtypes of non-muscle invasive bladder cancer

The majority of bladder cancers (BCs) are non-muscle invasive BCs (NMIBCs) and show the morphology of a conventional urothelial carcinoma (UC). Aberrant morphology is rare but can be observed. The classification and characterization of histologic subtypes (HS) in UC in BC have mainly been described in muscle invasive bladder cancer (MIBC). However, the currently used classification is applied for invasive urothelial neoplasm and therefore, also valid for a subset of NMIBC. The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known. HS in NMIBC are associated with an aggressive phenotype. Consequently, clinical guidelines categorize HS of NMIBC as "(very) high-risk" tumors and recommend offering radical cystectomy to these patients. Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials. Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively investigated in the context of HS in NMIBC. Further evaluation prior to implementation into clinical practice is needed.