OBJECTIVES: To assess the impact on medical decision-making by an in-vitro diagnostic test that predicts the risk of clinically recurrent prostate cancer following prostatectomy. METHODS: ProsVue™ is an FDA-cleared prognostic test that measures the linear slope of 3 ultrasensitive prostate-specific antigen levels over time. In the 510(k) clinical study, ProsVue was the strongest independent predictor of clinically recurrent prostate cancer in a 304-man cohort study. However, its clinical utility in adjuvant treatment decision-making has not yet been demonstrated. We prospectively enrolled men treated by radical prostatectomy in a multicenter, IRB-approved clinical trial. At postsurgical followup, urologist investigators (N=17) stratified each of their patients into a low, intermediate or high risk group for cancer recurrence based on clinicopathologic findings and documented their initial treatment plan. We employed the CAPRA-S postprostatectomy nomogram to standardize risk assessments across the investigative sites. After a patient’s ProsVue result was reported, urologists recorded whether or not the patient’s initial treatment plan was changed. The proportion of cases referred for secondary treatment before and after ProsVue and the significance of the difference was determined. RESULTS: Of 225 men reported; 128 (56.9%) were stratified into intermediate and high CAPRA-S risk groups. Investigators reported that they would have referred 41/128 (32.0%) at-risk men for adjuvant radiotherapy without ProsVue information. After results were known, investigators referred only 15/128 (11.7%) men. The difference in proportions (-20.3%, 95% confidence interval [CI] -29.9 to -10.3%) is significant (p <0.0001). Odds of a referral after the ProsVue result was reported was significantly reduced (Odds Ratio =0.28, 95% CI 0.15 to 0.54, p <0.0001). CONCLUSIONS: ProsVue has significant clinical utility in high-risk postprostatectomy cancer patients. A ProsVue result ≤2.0 pg/mL/month significantly reduced the proportion of urologists’ recommendations for adjuvant radiotherapy. Followup studies are needed to demonstrate whether or not ProsVue utilization reduces health care costs.