Circulating tumor (ct) DNA-based genomic profile of prostate cancer (PCa) patients with elevated carcinoembryonic antigen (CEA).

218Background: Neuroendocrine (aggressive variant) PCa patients often have elevated CEA (40-85%), which is associated with poor outcomes. We used ctDNA analysis to identify a genomic pattern for PCa patients with elevated CEA (CEA+ PCa). Methods: We analyzed ctDNA-based genomic profiles (Guardant 360) from 32 patients with CEA+ PCa. Profiles were compared with genomic profiles from the TCGA database, ctDNA profiles for 50 consecutive PCa patients with normal CEA levels (CEAnl PCa), and ctDNA profiles for GI tumors associated with elevated CEA. Results: CEA+ PCa patient profiles showed concordance with TCGA database genomic profiles for neuroendocrine PCa. There was high similarity in genes amplified; however many more single-nucleotide variants (SNVs) were detected with ctDNA analysis. For ctDNA profiles of CEA+ PCa, the most commonly amplified genes were AR, PIK3CA, MYC, CDK6, BRAF, MET; the most common clonal SNVs were in TP53, PTEN, APC, PIK3CA, and MET. Serial ctDNA analyses were done in 23 CEA+ PCa p...