The UroOnc Minute: Variant Histologies in Bladder Cancer, With Carissa Chu, MD

Welcome back to The UroOnc Minute!

In this episode of The UroOnc Minute, recorded at the 2026 American Urological Association Meeting, host Adam B. Weiner, MD, speaks with Carissa Chu, MD, about the evolving understanding of variant histology in bladder cancer and its implications for clinical practice. Chu, an assistant professor of urology at the University of California, San Francisco, notes that divergent differentiation or aberrant histology may be present in up to 40% of urothelial carcinomas, encompassing a broad spectrum of subtypes including micropapillary, plasmacytoid, sarcomatoid, squamous, glandular, and neuroendocrine variants. As nomenclature and classification continue to evolve, recognizing these histologic features remains critical for risk stratification and treatment planning.

Chu discusses recent research examining the genomic landscape of variant histologies, highlighting evidence that many of these tumors arise from a common urothelial precursor before evolving distinct morphologic and molecular characteristics.¹ She reviews findings demonstrating that certain subtypes, particularly plasmacytoid, sarcomatoid, and squamous variants, are associated with poorer outcomes independent of stage. The conversation also explores emerging molecular targets identified across different variant histologies, including HER2 alterations in micropapillary disease and other potentially actionable genomic changes that may help inform future precision medicine approaches.

From a practical standpoint, Chu emphasizes the importance of carefully characterizing variant histology in patients with muscle-invasive bladder cancer. She discusses factors that may influence prognosis, including the extent of variant involvement and the specific subtype present, and outlines the potential value of expert pathology review, molecular profiling, and referral to centers with clinical trial access. Looking ahead, she shares her enthusiasm for ongoing advances in bladder cancer therapeutics and advocates for greater inclusion of patients with variant histologies in clinical trials to ensure that emerging treatment strategies are evaluated in this historically underrepresented population.

REFERENCE

1. Chu CE, Chen Z, Whiting K, et al. Clinical Outcomes, Genomic Heterogeneity, and Therapeutic Considerations Across Histologic Subtypes of Urothelial Carcinoma. Eur Urol. 2025;88(5):472-481. doi:10.1016/j.eururo.2025.04.008.