OBJECTIVES: NADiA ProsVue is a prognostic system developed to identify men at lower risk for clinical recurrence of prostate cancer following radical prostatectomy, as indicated by a prostate-specific antigen (PSA) slope <=2 pg/mL/month.  We evaluated the potential cost-effectiveness of using the prognostic system to guide adjuvant radiotherapy (ART) in men considered to be at intermediate- or high-risk for recurrence based on the CAPRA-S nomogram.  METHODS: We developed a decision analytic model consisting of a decision tree to stratify men into risk groups and a state transition model to generate long-term costs and outcomes. We derived model parameters using patient-level data from the product’s 510(k) registration study, the medical literature and other sources.  We conducted probabilistic, one-way and two-way sensitivity analyses to examine the cost-effectiveness of the system (i.e. with PSA slope findings) versus standard care (i.e. without PSA slope findings). RESULTS: The cost-effectiveness of a PSA slope-guided strategy varied widely due to small differences in QALYs at 10 years.  Assuming that 20% of men in the intermediate-risk CAPRA-S group receive ART with standard care, the incremental cost-effectiveness ratio (ICER) is less than $50,000 per QALY when use of ART is less than 8.2% among men with PSA slopes <=2 pg/mL/month.  Assuming that 40% in the high-risk CAPRA-S group receive ART with standard care, ART would have to decrease to at least 11.5% among men with PSA slopes <=2 pg/mL/month to achieve an ICER less $50,000 per QALY.  ICERS were also sensitive to varying the costs of the prognostic system and ART, varying the benefits of salvage therapy and utility weights for ART toxicities. CONCLUSIONS: The ProsVue system has the potential to be cost effective, but its value will be dependent on the magnitude of reduction in ART among men identified as having a low risk of recurrence.