Among the estimated 230,000 men diagnosed with prostate cancer in the US each year there has been a rise in the number of radical prostatectomies (RP). There is some debate over the value of immediate adjuvant therapy following RP in men with high-risk pathological features versus delayed salvage radiation therapy when signs of disease progression are observed. Thus, it would be potentially useful to inform post-RP management strategies by more clearly identifying those patients at higher risk of progression and death from prostate cancer. A 22 gene-expression assay, Decipher® (GenomeDx Biosciences), has been developed in men treated with radical prostatectomy to predict the five-year risk of metastatic prostate cancer. Published and unpublished literature was evaluated to determine the analytic validity, clinical validity and clinical utility of Decipher. Limited information is available on the analytic validity of Decipher. In both discovery and validation studies, Decipher was shown to have good performance in discriminating men with metastasis from men without metastasis five years after surgery (AUC 0.75 to 0.90). In terms of clinical utility, no evidence was found reporting improved outcomes (lower prostate cancer specific mortality and treatment related adverse effects) from using this test to guide post-operative treatment. Four studies provided weak indirect evidence of clinical utility in which 31% to 43% of post-operative treatment recommendations were changed in men with high-risk prostate cancer based on test results, with 27% to 52% of treatment recommendations changing from any treatment to no treatment.