Currently, both clinicians and patients are faced with difficult treatment decisions when a diagnosis is made of prostate cancer because it is very difficult to predict whether a patient is likely to progress to aggressive, metastatic disease. Biomarkers that can predict the likely clinical outcome and recurrence for patients after surgical therapy are badly needed in order to aid clinicians in deciding on the appropriate course of treatment. We have developed a panel of biomarkers that is able to predict recurrence following surgery in our initial set of pilot cases. We plan to use three large sets of ethnically diverse patient samples with long-term, well-defined clinical follow-up data to validate these biomarkers that predict outcome for surgical therapy. Biomarker refinement and validation will be performed on platforms that are amenable to analysis of fixed tissues and ideal for rapid translation into widespread clinical use. Validation studies on separate groups of patients using biopsy specimens will be performed in a clinical laboratory environment at the Winship Cancer Institute Core Facilities to speed translation of these biomarkers. By the completion of the work in this proposal, we will have developed and validated a clinical lab test that could be translated to widespread use that would give doctors an idea what the best course of treatment is for patients with prostate cancer and help avoid unnecessary treatments. In the long run, this will result in better patient outcomes and reduced healthcare costs and treatment side effects.