Dna Repair Mutations And Treatment-Emergent Small Cell Neuroendocrine Prostate Cancer (T-Scnc) As Hallmarks Of Distinct Subgroups Of Metastatic Castration Resistant Prostate Cancer (Mcrpc): Data From The West Coast Prostate Cancer Dream Team.

5039Background: Genomic alterations in DNA repair genes are present in approximately 20-30% of patients with mCRPC. t-SCNC may be increasing in prevalence and is associated with adverse clinical outcomes. Potential overlap between these two subsets of mCRPC was assessed. Methods: Eligible patients (pts) underwent a metastatic tumor core needle biopsy at one of 5 centers. Tumor tissue was sent for consensus pathology call (JH, GT, LT) and targeted next-generation DNA sequencing. Chi-square test was used to compare the frequency of genomic alterations in select DNA repair genes (BRCA1, BRCA2, ATM, CDK12, RAD51, PALB2, FANCA, CHEK2, MLH1, MSH2, MLH3, and MSH6) between tumors with versus those without small cell histology. Frozen tissue from the same metastatic tumor underwent RNA sequencing (RNA-seq). Pts were prospectively followed for overall survival (OS). Results: 119 consecutive biopsies with sufficient tumor to permit histologic assessment and targeted NGS were included, including 14 biopsies (13%) wit...