The impact of variant histology on the outcome of bladder cancer treated with curative intent

Patient risk stratification is essential for optimal management of patients with bladder cancer. Risk status determines the application and timing of therapeutic interventions such as repeat transurethral resection, intravesical chemo- and immunotherapy, systemic chemotherapy, and radical cystectomy. One key factor in such risk stratification appears to be the presence of variant histologic patterns in the bladder tumor. More than 90% of tumors are conventional urothelial carcinoma, and the rest consist of urothelial carcinoma with aberrant differentiation (squamous/glandular differentiation, small cell carcinoma, sarcomatoid carcinoma, and micropapillary carcinoma) or nonurothelial carcinoma (squamous cell carcinoma and adenocarcinoma). In this review, we focus on the implications of aberrant differentiation on the management of patients with bladder cancer. All of the variant histologies portend a worse prognosis than pure urothelial carcinoma. Although radical cystectomy remains the mainstay of treatment in all forms of bladder cancer, we highlight the use of neoadjuvant chemotherapy in patients with subtypes responsive to such therapy.