1. The PCA3 Assay improves the prediction of initial biopsy outcome and may be indicative of prostate cancer aggressiveness de la Taille A, Irani J, Graefen M, Chun F, de Reijke T, Kil P, Gontero P, Mottaz A, Haese A. Clinical evaluation of the PCA3 Assay in guiding initial biopsy decisions. J Urol 2011;185:2119-25

2. Methods ► Prospective, multi-centre, European, real-life clinical practice study ► Evaluating the clinical utility of the PCA3 Assay in guiding initial biopsy decisions in 516 men with a serum total PSA level 2.5-10 ng/mL ► Informative rate 99% ► 40% had a positive biopsy *informative rate: percentage of urine samples that contain sufficient PCA3 mRNA and PSA mRNA to determine the PCA3 Score

3. Results: PCA3 predictive of initial biopsy outcome ► PCA3 Score higher in men with a positive than in those with a negative biopsy (median Score 50 vs. 18; P<0.0001) ► 2.7-fold higher probability of a positive biopsy in men with a PCA3 Score ≥ 35 than in those with a PCA3 Score < 35 PCA3 Score (N=207) P < 0.0001 (N=309)

4. ► The AUC ROC for predicting biopsy outcome was higher for PCA3 than for serum PSA, PSAD or %free PSA ► Inclusion of a PCA3 Score cut-off 35 in a multivariate model (including PCa risk factors age, digital rectal exam, serum total PSA, and prostate volume) increased the diagnostic accuracy from 0.737 to 0.792 (5.5%; P=0.03) Results: Diagnostic accuracy of PCA3 higher than PSA AUC ROCP-value vs PCA3 PCA3 Score (cut-off 35; N=516)0.761 Total PSA (ng/mL; N=513)0.577<0.0001 PSAD (ng/mL/cc; N=455)0.6890.0232 %free PSA (N=291)0.606<0.0001 AUC ROC: area under the receiver operating characteristic curve PSAD: PSA density

5. ► At a sensitivity of 80% and 90%, PCA3 Score had a higher specificity than serum PSA, PSAD or %free PSA Results: Specificity of PCA3 at sensitivity of 80% and 90% higher than PSA Specificity at:Sensitivity of 80%Sensitivity of 90% PCA3 Score58% (cut-off 22)37% (cut-off 13) Total PSA (ng/mL)44%30% PSAD (ng/mL/cc)27%15% %free PSA27%16%

6. ► PCA3 Score was significantly higher in men with biopsy Gleason score ≥7 vs. 33% vs. ≤ 33% positive cores and significant vs. indolent prostate cancer (PCa) according to Epstein biopsy criteria Results: PCA3 indicative of PCa significance P<0.0001

7. Conclusions ► This study shows that the PCA3 Score improves the prediction of initial biopsy outcome in men with a serum PSA level 2.5-10 ng/mL. An increasing PCA3 Score corresponded with an increasing probability of a positive initial biopsy ► The diagnostic accuracy of PCA3 was higher than that of total PSA, PSAD or %free PSA. Combining PCA3 with PSA and other PCa risk factors significantly increased diagnostic accuracy ► The PCA3 Score appeared to be indicative of PCa significance and may therefore aid in the selection of men with indolent PCa who can be managed with active surveillance