PCA3 Materials & News

de la Taille A, Irani J, Graefen M, Chun F, de Reijke T, Kil P, Gontero P, Mottaz A, Haese A. J Urol 2011;185:2119-25

• This prospective, multi-centre European real-life clinical practice study shows that the PCA3 Score improves the prediction of initial biopsy outcome in 516 men with a serum total prostate specific antigen (PSA) level 2.5-10 ng/mL and may be indicative of prostate cancer (PCa) aggressiveness.
• The informative rate was 99% (informative rate: % of urine samples providing sufficient mRNA for PCA3 analysis).
• Of the 516 men, 207 (40%) had a positive biopsy. The mean PCA3 Score was higher in men with a positive (69.6) than in those with a negative biopsy (31.0; P<0.0001; median values 50 vs. 18).
• The PCA3 Score cut-off of 35 provided the optimal balance between sensitivity (64%) and specificity (76%). Men with a PCA3 Score of ≥ 35 had a 2.7-fold higher probability of a positive biopsy (64%) than those with a PCA3 Score < 35 (24%, P<0.0001; Figure 1).
• Receiver Operating Characteristic (ROC) curve analysis revealed that the diagnostic accuracy for predicting initial biopsy outcome was statistically significantly better for the PCA3 Score than for total PSA, PSA density (PSAD) and %free PSA (Table 1).
• At a sensitivity of 80% and 90% the specificity was 58% and 37%, respectively, for the PCA3 Score (cut-offs of 22 and 13, respectively), vs 44% and 30% for PSAD, and 27% and 15% to 16% for total and %free PSA, respectively (Table 2).
• The PCA3 Score was significantly higher in men with biopsy Gleason score ≥7 vs < 7 (median 72 vs 40; P<0.0001), > 33% vs ≤ 33% positive cores (median 78.5 vs 39; P<0.0001) and significant vs indolent PCa according to Epstein biopsy criteria (median 57 vs 31; P=0.0016). The PCA3 Score may therefore be indicative for PCa significance and may aid in the selection of men to be managed with active surveillance (Figure 2).
• When using a PCA3 Score cut-off of 35, 60% of biopsies could be prevented while 11% PCa with a Gleason score ≥ 7 would be missed. Likewise, at a PCA3 Score cut-off of 20, 40% of biopsies could be prevented while 2% of PCa with a Gleason score ≥ 7 would be missed.
• In multivariate regression analysis, PCA3 was a strong risk factor for the presence of PCa, independent of  age, DRE outcome, serum total PSA level and prostate volume (P<0.001).
• 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) statistically significantly increased the diagnostic accuracy from 0.737 to 0.792 (5.5%; P=0.03).
• The results of this study show that the PCA3 Assay aids in the decision of which men need an initial biopsy and may aid in the selection of men who can be treated with active surveillance.

Figure 1. A PCA3 Score ≥ 35 is associated with a 2.7-fold higher probability of a positive biopsy than a PCA3 Score < 35

Figure 2. The PCA3 Score is higher in men with biopsy Gleason score ≥7 vs < 7, > 33% vs ≤ 33% positive cores and significant vs indolent PCa

 AUC ROC: Area Under the Receiver Operating Characteristic Curve

Editorial comment

This prospective European multi-centre study shows that the PCA3 Assay may not only have a good predictive potential in patients undergoing a repeat prostate biopsy, but also in biopsy-naive patients with a PSA 2.5-10 ng/mL. Deras et al. (J Urol 2008;179:1587-92) have also reported that the performance of the PCA3 Assay is similar in men scheduled for a first or repeat biopsy. In addition, the test appears to be predictive of clinically insignificant prostate cancer. The clinical relevance of PCA3 testing is that PCA3 testing at a cut-off of 35 could prevent up to 60% of initial biopsies while missing 11% of tumours with a Gleason score ≥ 7. At a PCA3 Score cut-off of 20, 40% of biopsies could be prevented while only 2% of tumours with a Gleason score ≥ 7 would be missed. Avoiding unnecessary biopsies is very important in light of the discomfort and pain related to prostate biopsies and the risk of complications (including hospitalisation in 4% of patients) associated with the procedure.

More information: Article at PubMed