Episode 12: Variant Histology Treatment Considerations From World GU 2025

As part of the latest Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, went to the 2025 World Conference on Genitourinary Cancers (World GU) to speak with various experts about key developments in genitourinary oncology. In one discussion, Bupathi and Garmezy convened with Bradley G. Somer, MD, to exchange ideas about the management of genitourinary cancers with variant histologies, which included patients with prostate cancer, bladder cancer, and kidney cancer.

The group first highlighted potential treatment strategies for prostate cancer subgroups such as those with small cell histology or neuroendocrine differentiation. The discussion explored the roles that modalities such as androgen deprivation therapy, chemotherapy, and radiation may play in the care of patients with prostate cancer harboring variant histologies, especially in the context of a community oncology setting.

Next, the conversation focused on strategies for managing papillary, plasmacytoid, small cell, and other disease variants in the context of bladder cancer. Based on previously published data and prior clinical experience, the group discussed the appropriate circumstances for using regimens such as enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) or other immunotherapy approaches depending on how a patient presents with bladder cancer.

Additionally, the group reviewed strategies for managing clear cell, papillary, and chromophobe variants in kidney cancer along with other disease histologies. The experts detailed key factors for deciding on how to sequence VEGF inhibitors and other tyrosine kinase inhibitor combinations based on the observed histology.

Bupathi is executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers. Garmezy is associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers. Somer is a medical oncologist, senior partner on the Executive Cancer Council, and president at West Cancer Center & Research Institute.