Background: Approximately 30% of patients will have ≥pT3 disease and/or positive surgical margins at radical prostatectomy (RP), indicating a high risk of local recurrence. While current guidelines recommend consideration of adjuvant radiotherapy (aRT) in this setting, < 10% undergo aRT. The Decipher assay is a novel, tissue-based genomic classifier (GC) developed and validated in the post-RP setting as a predictor of metastasis. Current retrospective evidence suggests that patients with a high GC score may benefit from aRT, while observation may be safe for those with a lower GC score. However, there are no randomized prospective data evaluating the clinical utility of biomarkers in men with adverse features after RP. Here we see to determine the impact of GC test results on adjuvant treatment decisions for high-risk post-RP patients vs. clinical factors alone. Methods: Genomics in Michigan ImpactiNg Observation or Radiation (G-MINOR) is a 4-year (12-month enrollment, 3-year follow-up) prospective, cluster-crossover, unblinded, study of 350 subjects from twelve Urology practices in the Michigan Urological Surgery Improvement Collaborative (MUSIC). MUSIC is a physician-led quality improvement consortium nearly all academic and community urology practices within the state of Michigan. Each clinical center participating in this trial will be randomly assigned to either a Genomic Classifier (GC)-based strategy or control arm for a period of 3 months. Patients in both arms will receive a predicted risk of recurrence based on a validated clinical nomogram, the CAPRA-S score, enabling a head-to-head comparison of the Decipher assay with a freely-available validated prognostic tool. Random assignments will be generated centrally by a study statistician and provided to centers immediately before commencing enrollment in each 3-month period. Each center will have two GC and two UC enrollment periods, maintaining study-wide balance and blinding of assignments in subsequent periods. Patients will be followed for receipt of adjuvant therapy as well as oncologic (recurrence, metastasis, and death) and patient-reported quality of life. Clinical trial information: NCT02783950