The prostate cancer gene 3 (PCA3) urine test in men with previous negative biopsies: does free-to-total prostate-specific antigen ratio influence the performance of the PCA3 score in predicting positive biopsies?

OBJECTIVE To determine the performance characteristics of the prostate cancer gene 3 (PCA3) score on the outcome of biopsy relative to different ranges of free-to-total prostate-specific antigen (PSA) ratio (f/tPSA) in men with a previous negative biopsy and a PSA level of 2.5-10 ng/mL, as urine tests like PCA3 are currently under investigation in order to improve prostate cancer diagnosis and to decrease the rate of unnecessary rebiopsies. PATIENTS AND METHODS Data from the previous prospective European multicentre study were reviewed. Only patients with a PSA level of 2.5-10 ng/mL were included in the present study. In all, 301 patients had complete data. The diagnostic accuracy of the PCA3 score for predicting a positive biopsy outcome was studied using sensitivity, specificity, negative and positive predictive values. The PCA3 performance was evaluated relative to three different subgroups of f/tPSA, as follows: > 20% (group 1), 10-20% (group 2) and < 10% (group 3). RESULTS The prostate cancer detection rates were 18.8%, 23.9% and 34.8% in groups 1, 2 and 3, respectively. The area under the receiver operating characteristic curve of the PCA3 score, total PSA and f/tPSA was 0.688, 0.553 and 0.571, respectively. The percentage of men with positive biopsies was 30.6%, 37.0% and 44.4% in those with a PCA3 score of > 30, vs 10.3%, 15.5% and 28.6% when the PCA3 score was < 30, in groups 1, 2 and 3, respectively. The difference was significant only in groups 1 and 2. In men with a f/tPSA of < 10% the difference in detection rates relative to the PCA3 score was not statistically significant regardless of which PCA3 threshold was used. A high PCA3 score was significantly associated with age, clinical T2 stage and positive biopsy (P < 0.001, 0.013 and < 0.001, respectively). In bivariate analysis accounting for the PCA3 score and the f/tPSA, a PCA3 score of > 30 was a significant independent predictor of positive biopsies (odds ratio 3.01; 95% confidence interval 1.74-5.23; P < 0.001). CONCLUSIONS PCA3 remained a better predictor of prostate cancer than f/tPSA. In men with a f/tPSA of > 10%, the use of the PCA3 score was highly correlated with the risk of having cancer on re-biopsy, and could prevent unnecessary prostate biopsies if the value is low.