Background: Prostate cancer is a leading cause of cancer-related mortality with a 5-year survival rate of 69%. In this study, we examine the role of integrating CGP, including tissue and liquid biopsy testing, into the clinical management of prostate cancer patients. Methods: We analyzed 140 cases of advanced prostate carcinoma with tissue and ctDNA based Comprehensive Genomic Profiling (CGP). CGP analysis revealed genomic alterations (GAs), TMB and MSI status. Germline testing, using multiple commercially assays was also obtained. Results: The median age of patients tested by tissue-based and liquid-based CGP was 65 years (46 to 85 yrs) and 69 years (51 to > 89 years), respectively. CGP analysis of tissue samples revealed the most commonly altered genes to be TP53 (34.6%), TMPRSS2-ERG (25.9%), PTEN (23.5%), NBN (14.8%), MYC (13.6%), BRCA2 (14.3%) and CDKN2A (13.3%). TMB analysis determined in 77 tissue samples showed a median (mean) value of 2.61 (5.00) mutations/Mb. 3.9% cases (3/77) were found to be hypermutated. MSI status was determined in 74 cases of which 2.7% (2/74) were found to be MSI-High. Of the tissue-based samples tested, 30.9% (25/81) were derived from metastatic sites. Analysis of commonly altered genes between primary vs metastatic tissue samples revealed TP53 mutations were significantly enriched in metastatic tumors. CGP analysis of the 59 liquid biopsy samples revealed the most commonly altered genes to be TP53 (37.3%), NF1 (10.2%), ATM (10.2%), CHEK2 (8.5%) and GNAS (8.5%). Germline testing was performed as described above on a clinically indicated subset of patients, which revealed alterations in BRCA, ATM, CHEK2, BRIP1 and TP53, among others. We are evaluating additional patient samples as part of the data set, which will be added to the final abstract presentation with a cutoff date of 12-31-2019. Conclusions: Genomic testing for high risk and advanced prostate cancer patients per the NCCN recommendations, with somatic testing, using tissue and liquid biopsy testing, as well as germline testing in selected cases, identifies DNA alterations which have potential clinical utility for clinical trial enrollment.