ASCO GU 2020: Comprehensive Genomic Profiling (CGP) of Histologic Subtypes of Urethral Carcinomas (UrthCa)

San Francisco, CA (UroToday.com) Urethral carcinoma is an uncommon malignancy, that accounts for less than 1 percent of all malignancies. It commonly presents in late stages having progressed to advanced metastatic disease. Unfortunately, these patients tend to respond pooly to standard treatments and there is a need for more effective therapy.

To that end, Dr. Joseph Jacob presented his group's work utilizing genomic alterations to better characterize disease subsets. Samples from 126 patients underwent hybrid-capture based CGP to evaluate genomic alterations. The tumor mutational burden and microsatellite instability were assessed, as was PD-L1 expression. The specimens were representative of this heterogeneous disease with 49 (39%) urothelial cases, 31 (24%) squamous cases, 34 (27%) adenocarcinomas cases, and 12 (9%) clear cell cases.

First, the team highlighted differences on the basis of histologic classifications. Urothelial disease and squamous cells were more common in men, while adenocarcinoma and clear cell were more prevalent in women. Looking deeper at the genomic signature specific genes were more prominently effect in specific histologies.  For instance, ERBB2 mutations were present in all subtypes, while FGFR1-3 was present in squamous cell and BRAF in adenocarcinoma. These alterations have known therapeutic targets and might one day help guide clinicians in medication selection (table).

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Specifically, Dr. Jacob hypothesized that these alterations were responsible for the associated higher TMB and PD-L1 staining levels seen in urothelial and squamous subtypes that were appreciated in this study. He next highlighted the specific implications of this observation for future targeted immunotherapy.

Overall, this talk reflected on a general theme of the conference, specifically, the need to be more selective with our current therapies. While not readily applicable to current clinical practice, his talk highlighted exciting basic research that will help move us forward towards this eventual goal.

Presented by: Joseph Jacob, MD, Assistant Professor of Urology, Upstate Medical University, Syracuse, New York

Written by: Adrien Bernstein, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Fox Chase Cancer Center, Philadelphia, PA at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California

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