OBJECTIVES: Active Surveillance (AS) is increasingly recommended as a viable management option for many patients with clinically low risk prostate cancer (PCa). Genomic testing assesses tumor biology, provides an independent and individualized risk assessment, and has the potential to optimize care. Here, we assessed the economic impact of genomic testing by assessing the influence of a 17-gene panel (Oncotype DX® Genomic Prostate Score™, GPS) on treatment selection and healthcare costs in patients with NCCN Very Low, Low, and Intermediate risk PCa.   METHODS: We conducted a chart based analysis for 1087 men with NCCN Very Low, Low, and Intermediate risk PCa managed in four large urology practices (LUP). Shared treatment decisions, with GPS testing, were captured through electronic health records from May 2014 through July 2016. Active Surveillance (AS) was defined as documented AS or lack of treatment documentation within six months of prostate cancer diagnosis. We estimated economic outcomes using peer-reviewed and published cost numbers from baseline (untested) and tested patients from a fifth LUP.   RESULTS: Baseline (untested) practice patterns in the LUP from which cost data was available included 32% of men following AS, 37% receiving Radical Prostatectomy (RP) and 29% Radiation Therapy (IMRT). In the 5 LUPs with GPS testing, AS, RP and RT were utilized by 59%, 20% and 9% of patients, respectively. In these practices, utilization of GPS was calculated to result in a total savings of $5.574M ($5,128 per-patient) over the first 180 days post-diagnosis, including GPS list price. We estimate that a 2M member commercial payer that tests all appropriate localized PCa patients with GPS would result in approximately $4.5M in savings. CONCLUSIONS: In this economic assessment, using real-world cost data and GPS guided treatment selection, we project that GPS utilization would decrease direct healthcare spend through appropriate treatment selection for clinically low-risk PCa patients.