ASCO GU 2018: Best of Journals: Urothelial Carcinoma

San Francisco, CA (UroToday.com) In this session, Dr. Huddart discussed various articles published in 2017 focusing on translational aspects of urothelial carcinoma. The first topic Dr. Huddart examined was molecular subtypes and phenotypes of urothelial carcinoma. Five expression profiles have been identified in the literature: luminal papillary, luminal infiltrated, luminal, basal squamous, and neuronal. Of which, basal squamous and luminal papillary were most commonly seen. The luminal papillary group tends to be lower stage and higher purity. Basal squamous tends to have squamous features, low purity with a lymphocytic infiltrate. Key genetic features are linked with each subtype. Improved overall survival was correlated with the luminal subtype in the non-neoadjuvant chemotherapy cohort. However, in the neoadjuvant chemotherapy cohort, the basal subtype had the greatest overall survival.

Subsequently, Dr. Huddart also discussed molecular subtyping and response to radiotherapy. Basal subtype cancers treated with radiotherapy with carbogen and nicotinamide had improved overall survival compared to radiotherapy alone. However, in the luminal subtype this pattern was not seen.

Gene mutations have been mapped in bladder cancer patients. P53 pathway has been found to be inactivated in 89% of case. Rb1 was involved in 17%, ATM 15%, ERCC2 9% and RAD51 2%. Genomic characterization of upper tract urothelial carcinoma has been performed as well. Looking at 31 patients, a different pattern and frequency and mutations was seen compared to bladder cancer patients. Four clusters of patients based on DNA mutations were identified.

A randomized controlled trial evaluating Lapatinib in HER 1/2 positive urothelial carcinoma was performed. However, no differences in progression free (primary endpoint) or overall survival (secondary endpoint) was demonstrated.

In conclusion, Dr. Huddart stated that the understanding of urothelial carcinoma genetics has moved rapidly over the past 2 years. Patients with urothelial carcinoma can be subdivided by RNA and DNA subgroups that may be prognostic. It is unknown at this time whether these differences predict treatment response. Continued investigations in translational medicine are needed to evaluate how this information will influence clinical practice.

Speaker: Robert A. Huddart, MBBS, MRCP, FRCR, PhD, Institute of Cancer Research and Royal Marsden Hospital

Written by: David B. Cahn, DO, MBS, Fox Chase Cancer Center, Twitter: @dbcahn at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA

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