Plasminogen activation inhibitor-1 improves the predictive accuracy of prostate cancer nomograms

Purpose: We tested whether the addition of preoperative circulating plasminogen activator inhibitor type I levels improves the accuracy of standard preoperative and postoperative models for prediction of biochemical recurrence after radical prostatectomy. Materials and Methods: Preoperative plasma levels of plasminogen activator inhibitor type I were measured in 429 consecutive patients treated with radical prostatectomy for clinically localized prostate cancer. The patients were randomly divided into a development (67%, 286) and a split sample validation cohort (33%, 143). Cox regression analysis was used to develop prognostic nomograms for prediction of biochemical recurrence. Results: In standard univariate analyses categorically coded preoperative plasminogen activator inhibitor type I was significantly associated with biochemical recurrence (p < 0.001). In standard preoperative and postoperative multivariate analyses preoperative plasminogen activator inhibitor type I was independently associated with biochemical recurrence (p < 0.001 and p = 0.002, respectively). In the split sample validation cohort the addition of plasminogen activator inhibitor type I increased the predictive accuracy of the preoperative multivariate model by 1.2%, 7.7%, 10.3%, 6.7% and 5.4% at 1, 2, 3, 4 and 5 years, respectively (p values < 0.001). Moreover, the addition of plasminogen activator inhibitor type I increased the predictive accuracy of the postoperative model by 0.5%, 1.1%, 4.0%, 2.4% and 3.6% at 1, 2, 3, 4 and 5 years, respectively (p values < 0.001). Conclusions: Preoperative circulating plasminogen activator inhibitor type I is a predictor of biochemical recurrence, and it enhances the accuracy of preoperative and postoperative nomograms. After external validation these nomograms may assist clinical decision making regarding treatment choice and followup as well as identification of patients at high risk for biochemical recurrence who may benefit from neoadjuvant and/or adjuvant treatment.