174 Background: We have performed genomic analysis of circulating tumor DNA (ctDNA) to identify actionable anomalies in 55 patients with metastatic prostate cancer. Methods: A publically-accessible assay (Guardant Health) was used to analyze 68 known cancer genes for anomalies (missense mutations, amplifications) by a digital PCR technique. The racial profile included Caucasian (27), African-American (27), Asian (1) patients. Most subjects (82%) had CRPC and had been treated with multiple forms of androgen deprivation and chemotherapy. Results: Genomic anomalies were found in 52/55 subjects. 127 missense mutations and 78 amplifications were identified in 35 genes. Missense mutations in each gene were overwhelmingly single (98/127). African-American patients each had an average of 3.9 genomic anomalies, whereas Caucasian patients each had an average of 2.7 anomalies (p = NS). Anomalies most commonly involved TP53 (43.2%), AR (43.4%), MYC (21.8%), BRAF (21.8%), and DNA repair genes (BRCA1, BRCA2, or ATM; 16.4%). Taxane-based chemotherapy was given to 24/55 subjects with mCRPC. These 24 patients were grouped by TP53 status (WT, n = 13; MUT, n = 11) and progression-free survival (PFS) was determined by PCWG2 criteria (PSA or imaging). Data for PFS vs time were presented as Kaplan-Meier plots and compared by the log rank test. Median PFS during taxane chemotherapy was approximately twice as long for subjects with MUT TP53, compared with that of subjects with WT TP53 (p = 0.013; HR = 2.5 [1.1-6.0]). Conclusions: 1. Genomic analysis on ctDNA from patients with metastatic prostate cancer is feasible and identifies anomalies in most patients. 2. Within the limits of the assay, ctDNA analysis provides similar findings to those identified by analysis of FFPE tissue (Robinson et al., Cell, 2015). 3. ctDNA analysis can identify missense mutations that are associated with an improved PFS from taxane-based chemotherapy. ctDNA analysis may help clinicians to judge the potential benefits of chemotherapy in subjects with mCRPC.