Implications for diagnosis and treatment strategies in non-muscle invasive bladder cancer with variant histology: a systematic review

INTRODUCTION: The identification of variant histology (VH) has been recognized as a critical element in the diagnos-tic pathway of bladder cancer (BCa), both for prognostic and therapeutic implications. However, the current evidence on the oncological outcomes of patients harboring VH BCa mostly derives from studies including muscle-invasive disease. Consequently, the correct management of patients with non-muscle invasive bladder cancer (NMIBC) and VH is limited and conflicting, and the optimal therapeutic approach remains therefore controversial. EVIDENCE ACQUISITION: In this review, we aimed at reporting the current evidence on NMIBC with VH. EVIDENCE SYNTHESIS: Despite a constant increase in VH reporting at transurethral resection of bladder tumor (TURBT) specimens as compared to previous decades, we found that the incidence of VH is still sparse among studies. Furthermore, the agreement between TURBT and radical cystectomy (RC) specimens in VH identification is another matter of debate. Currently, most of the included studies report a poor overall concordance, especially for the micropapil-lary variant. Finally, while squamous and micropapillary variants are those associated with the worst survival outcomes, immediate RC is mostly considered for micropapillary tumors. Conversely, the survival benefit of immediate RC as com-pared to bladder-sparing approaches (i.e., BCG immunotherapy) for the other types of VH BCa is still an open question owing to the paucity of data available. CONCLUSIONS: Thus, in these patients, BCG treatment could be proposed considering the need for more intensive oncological surveillance.