OBJECTIVES: Prostate Cancer (PCa) disease management for intermediate-risk patients is challenging due to the uncertainty in risk at the time of biopsy.  Novel prognostic tools that better estimate the risk of disease progression post-biopsy may save costs and improve quality of life by directing patients to more appropriate treatments.  We analyzed the cost of PCa management for patients stratified as intermediate-risk by American Urological Association (AUA) guidelines.  Management strategies were modeled according to standard care and following a new prognostic tool, Prostate Px®+.  The new test employs morphologic and biomarker features, in addition to the AUA clinical-pathologic ones, to predict PCa disease progression at biopsy. METHODS: A cost-minimization analysis was performed on a multi-institution cohort of 399 AUA intermediate-risk patients. Px+ reclassified 69% of patients as low-risk and 31% as high-risk. A decision analysis model was developed, accounting for five primary treatments (radical prostatectomy (RP), radiation therapy, primary hormonal therapy, brachytherapy and active surveillance) plus secondary treatments. Standard management for AUA intermediate-risk was compared with management post Px+ reclassification.  Patients reclassified as low-risk were assumed to follow low-risk treatment distributions and disease progression; those reclassified as high-risk were assumed to follow high-risk treatment distributions and disease progression.  The model was informed with costs and probabilities from the literature and analyzed from Medicare’s perspective with a 10 year time horizon.   RESULTS: The expected cost per patient of standard management was $30,287 and $27,987 for Px+ (including the $2,968 list price), resulting in an expected cost savings of $2,300. One-way sensitivity analysis confirmed that modeled management post Px+ saves costs for all variables except for certain values of recurrence probabilities post RP in low-risk and intermediate-risk patients. CONCLUSIONS: Novel personalized risk assessment tools such as Px+ improve PCa risk stratification, impacting disease management and potentially saving costs over current standards.