1390P Circulating tumor DNA (ctDNA) and prognosis with PSMA-targeted radionuclide therapy (TRT)

PSMA-TRT is approved for mCRPC based upon demonstrated overall survival (OS) advantage. However, even after pre-selection by PSMA imaging, not all patients respond (54% without PSA50 response in the VISION study). In addition to dose (which likely related both target expression and amount of radioactivity administered), prognostic genomic factors that may relate radiosensitivity exist. Collection real-time tissue biopsies setting presents challenges might be overcome with use ctDNA. Germline control + plasma DNA were obtained prior treatment 2 prospective trials assayed utilizing PCF SELECT (Specific Evaluation Liquid Established prostate Cancer Targets) platform. Variables interest included AR copy number (wild-type vs gain), homologous recombination repair (HRR) gene loss), allele-specific ploidy (asP; diploid high). asP a novel metric instability loss heterozygosity, computed as weighted mean chromosomes (Ciani et al. Cell Systems 2022). Cox regression modelling was used assess association these variables clinical outcome measures >50% PSA (PSA50) OS. 80 received (177Lu-PSMA-617 n=50; 225Ac-J591 n=30). High associated poorer OS (HR 2.14, 95% CI 1.15-4, p=0.017) trend lower rates achieving (OR 0.48, 0.16-1.47, p=0.20). gain 2.69, 1.40-5.18, p=0.003) 0.47, 0.14-1.49, this study, HRR differential responses or Similar results combined study when individual studies 177Lu-PSMA-617 analyzed asP. ctDNA analysis, non-invasive technique, undergoing demonstrate high ploidy, reflecting complex karyotype, are prognosis.