Variant histology: Role in management and prognosis of nonmuscle invasive bladder cancer

Purpose of review: The true clinical significance of variant histology is controversial and diagnosis is challenging, especially in the setting of nonmuscle invasive (NMI) disease. If the presence of variant architecture in NMI identifies a high-risk population with a worse prognosis and better suited for early aggressive intervention (i.e., radical cystectomy), then treatment recommendations should reflect this notion. This review outlines the current evidence and determines whether histologic variants should change management of patients with nonmuscle invasive bladder cancer. Recent findings: Patients with high-risk NMI tumors and variant histology should be offered early cystectomy, especially if harboring pure squamous, adenocarcinoma, sarcomatoid, plasmacytoid, or micropapillary disease. In patients with small cell disease, systemic primary chemotherapy is the ideal option followed by local therapy for primary tumor control. For squamous/glandular differentiation, nested variant, and other rare variants, intravesical therapy is an option based on standard risk stratification in patients with NMI disease. Diligence is needed in the presence of variant histology to minimize the risk of understaging as well as close surveillance to not compromise the opportunity of cure. Summary: The management of nonmuscle invasive bladder cancer with variant histology is challenging, largely in part to the high risk of understaging and the background of already existing controversy regarding the management of high-risk NMI disease for standard urothelial cell carcinoma (early cystectomy vs. intravesical therapy). Future studies should be focused identifying if variant architecture confers different tumor biology than that of pure urothelial carcinoma, and if this difference translates into innovations in bladder sparing therapies.