Should histologic variants alter definitive treatment of bladder cancer?

The clinical significance of variant histology is controversial and diagnosis is challenging. If variant architecture truly identifies high-risk patients, or those with a differential response to therapy, than treatment algorithms should be altered. This review outlines the current evidence and determines whether histologic variants should indeed alter definitive treatment.

For patients with pure squamous cell, adenocarcinoma, or small cell carcinoma, there is clear evidence to alter treatment paradigms. In adenocarcinoma or squamous cell carcinoma, there is a focus on local control and multimodal therapy with radiation. In small cell carcinoma all stages should be treated with primary chemotherapy followed by surgical extirpation. For patients with other variants of urothelial differentiation (i.e., micropapillary, sarcomatoid, squamous/glandular differentiation, etc.), management guidelines are less clear and radical cystectomy remains the mainstay of treatment at this time.

The management of variant histology is challenging as it not only depends on accurate diagnosis and staging, but on assumptions regarding sensitivity to multimodal therapy (i.e., chemotherapy, radiation, intravesical agents) based on a handful of retrospective case series. This will need to be the focus of future studies and collaborative efforts in order to make significant advancements in the field.