Clinical evaluation of the PCA3 assay in guiding initial biopsy decisions

We evaluated the clinical utility of the PCA3 assay in guiding initial biopsy decisions in prostate cancer. A European, prospective, multicenter study enrolled men with a serum total prostate specific antigen of 2.5 to 10 ng/ml scheduled for initial biopsy. After digital rectal examination first catch urine was collected. PCA3 scores were determined using the PROGENSA(®) PCA3 assay and compared to biopsy outcome. The diagnostic accuracy of PCA3 was compared to total prostate specific antigen, prostate specific antigen density and %free prostate specific antigen. In 516 men the positive biopsy rate was 40%. An increasing PCA3 score corresponded with an increasing probability of a positive biopsy. The mean PCA3 score was higher in men with a positive vs a negative biopsy (69.6 vs 31.0, median 50 vs 18, p <0.0001). The PCA3 score was independent of age, total prostate specific antigen and prostate volume. The PCA3 score (cutoff of 35) had a sensitivity of 64% and specificity of 76%. ROC analysis showed a significantly higher AUC for the PCA3 score vs total prostate specific antigen, prostate specific antigen density and %free prostate specific antigen. The PCA3 score was significantly higher in men with biopsy Gleason score 7 or greater vs less than 7, greater than 33% vs 33% or fewer positive cores and significant vs indolent prostate cancer. Inclusion of PCA3 in multivariable models increased their predictive accuracy by up to 5.5%. The PROGENSA PCA3 assay can aid in guiding biopsy decisions. It is superior to total prostate specific antigen, prostate specific antigen density and %free prostate specific antigen in predicting initial biopsy outcome, and may be indicative of prostate cancer aggressiveness