Individual risk prediction of high grade prostate cancer based on the combination between total prostate-specific antigen (PSA) and free to total PSA ratio

Objectives: Clinical practice guidelines endorse the stratification of prostate cancer (PCa) risk according to individual total prostate-specific antigen (tPSA) values and age to enhance the individual risk-benefit ratio. We defined two nomograms to predict the individual risk of high and low grade PCa by combining the assay of tPSA and %free/tPSA (%f/tPSA) in patients with a pre-biopsy tPSA between 2 and 10 mu g/L.Methods: The study cohort consisted of 662 patients that had fPSA, tPSA, and a biopsy performed (41.3% with a final diagnosis of PCa). Logistic regression including age, tPSA and %f/tPSA was used to model the probability of having high or low grade cancer by defining 3 outcome levels: no PCa, low grade (International Society of Urological Pathology grade, ISUP < 3) and high grade PCa (ISUP >= 3).Results: The nomogram identifying patients with: (a) high vs. those with low grade PCa and without the disease showed a good discriminating capability (similar to 80%), but the calibration showed a risk of underestimation for predictive probabilities > 30% (a considerable critical threshold of risk), (b) ISUP50%. In ISUP 5 a possible loss of PSA immunoreactivity has been observed.Conclusions: The estimated risk of high or low grade PCa by the nomograms may be of aid in the decision-making process, in particular in the case of critical comorbidities and when the digital rectal examinations are inconclusive. The improved characterization of the risk of ISUP >= 3 might enhance the use for magnetic resonance imaging in this setting.