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AUA 2017

AUA 2017: Studying Niche Populations: Neuroendocrine Prostate Cancers

Boston, MA (UroToday.com) Dr. Beltran offered a certifiably dizzying account of the rapid and widespread molecular characterization of metastatic castrate resistant prostate cancer (mCRPC). Her group and others have been busy! Castrate resistant prostate cancer is a clinically heterogeneous disease with disparate outcomes and efforts have started to molecularly subclassify CRPC based on molecular alterations (genes include BRCA2, ATM, TP53, PIK3CA, among others). Notably, these genes are commonly targetable, and may guide therapy with new agents. She described that neuroendocrine (NE) tumors are usually androgen "indifferent" and PSA independent, but can co-exist with androgen sensitive clones. Dr. Beltran undertook a phenotype to genotype approach using patients with small cell/NE prostate cancer with survival less than one year. Working with the Rubin group, they compared the genomic expression of both AR dependent and independent tumors. She provided some mechanistic evidence of RB1 and TP53 in lineage plasticity and driving the NE phenotype. She next described the importance of N-Myc mutations in driving NEPC in mouse models, which may be targetable.

When does AR resistant phenotype arise? Studies of single patients with multiple samples suggested divergent clonal evolution, with therapeutic and diagnostic implications. I.e., we may not be able to detect or predict the presence of NEPC until it occurs late in the disease process (and under selective treatment pressure). This makes liquid biopsy extremely important in this disease process and some of her unpublished data suggested that liver metastases may provide relatively higher ctDNA levels, compared with nodal metastasis. Furthermore, she shared ctDNA data that there may be less molecular heterogeneity in NEPC compared with CRPC adenocarcinoma.

She concluded by emphasizing that there are currently no approved therapies specifically for this disease state. In her group, they are generally giving platinum + either etoposide (if small cell) or docetaxel (if mixed with adenoCA).

Presented by: Himisha Beltran, Cornell University New York

Contributed by: Jed Ferguson, MD/PhD and Ashish Kamat, MD. MD Anderson Cancer Center, Department of Urology.

at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA