Abstract 41: Multi-focal genomic dissection of synchronous primary and metastatic tissue from de novo metastatic prostate cancer

Background: 10% of newly diagnosed prostate cancer presents with metastases. Known as de novo metastatic castrate-sensitive prostate cancer (mCSPC), it is disproportionally responsible for >50% of prostate cancer deaths. Cancer genotyping can identify vulnerabilities exploitable by targeted therapies, and promises to help prognosticate. However, tissue from de novo mCSPC is scarce; neither prostatectomy nor metastatic biopsy is standard, and it is unknown if diagnostic biopsies are representative of synchronous metastases. The potential for plasma circulating tumor DNA (ctDNA) to inform on tumor genotype is also unknown. Methods: We performed comprehensive pathological and genomic assessment of all spatially or phenotypically-distinct tumor foci (n=523) in 43 patients with de novo mCSPC who underwent prostatectomy, pelvic lymph node dissection, and plasma collection. Results: 91% (478/523) of tissue foci had evidence of prostate cancer by targeted DNA sequencing, with a median tumor fraction of 48%. When modeling random selection of a single primary foci (mirroring biopsy tissue availability in clinic), tumor fraction was