Characterization of neuroendocrine prostate cancer (NEPC) in patients with metastatic castration resistant prostate cancer (mCRPC) resistant to abiraterone (Abi) or enzalutamide (Enz): Preliminary results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT).

5003 Background: Mechanisms of resistance to androgen signaling inhibitors such as Abi or Enz are poorly understood. An increasing % of these pts develop NEPC. Pathologic (path), clinical, and genomic characterization of pts with NEPC was undertaken in the context of the WCDT project, which seeks to identify genetic pathways underlying primary and acquired resistance to Abi and Enz. Methods: Eligible mCRPC pts underwent a metastasis (met) biopsy (bx) at one of 5 WCDT centers, using a standardized bx protocol, and were uniformly followed for clinical outcomes. Tissue was both frozen, and formalin fixed/paraffin embedded. Independent path review was undertaken by 3 pathologists. Frozen specimens underwent laser capture micro-dissection, RNA isolation, library preparation and RNA sequencing (seq). Machine learning was used to derive a NEPC expression signature. Results: 150 of 300 planned mCRPC pts have undergone bx. Path review has been undertaken in 101. Classic small cell cancer (SmCC) was identified in 1...