Beyond the Abstract - Clinical Evaluation of the PCA3 Assay in Guiding Initial Biopsy Decisions , by Alexandre de la Taille, MD., Et Al

BERKELEY, CA ( - This prospective, open-label, multi-centre European study evaluated the clinical utility of the PROGENSATM PCA3 (Prostate CAncer gene 3) Assay in guiding initial prostate biopsy decisions in men with suspicion of prostate cancer (PCa). Briefly, the results show that the PCA3 Score improves the prediction of initial prostate biopsy outcomes in these men and may be suggestive of PCa aggressiveness.


The PCA3 Assay is CE-marked and been commercially available in Europe since November 2006. It has the ability to detect and quantify PCA3 mRNA in urine samples. Its development was based on the finding that PCA3 mRNA has a much higher expression in malignant (i.e. tumour or metastatic) than in benign and normal prostate tissue. Therefore, it was believed that PCA3 may act as a marker for PCa. Recently, the PCA3 Assay has shown promise in guiding repeat prostate biopsy decisions and in differentiating clinically significant from insignificant (indolent) PCa [1-7]. The current study examined its usefulness in guiding initial biopsy decisions.

Post-digital rectal examination (DRE) urine samples were collected from 516 men with a serum total prostate specific antigen (PSA) level 2.5-10 ng/mL scheduled for initial prostate biopsy and PCA3 Scores were determined. The informative rate was 99%, which means that 99% of urine samples provided sufficient mRNA for PCA3 analysis, confirming the robustness of the test and ease of use in clinical practice.

It was found that the probability of having a positive initial biopsy increased with increasing PCA3 Scores. Men who had a positive biopsy (40% of men) had in general higher mean PCA3 Scores than those with a negative biopsy (69.6 vs 31.0; median values 50 vs 18, P<0.0001), with the scores being independent of age, total PSA and prostate volume. The optimal balance between sensitivity (64%) and specificity (76%) of the PCA3 Assay was achieved at a PCA3 Score cut-off of 35. Men who had a PCA3 Score ≥ 35 (64%) had a 2.7-fold higher probability of a positive biopsy than those with a PCA3 Score < 35 (24%, P<0.0001). It was deducted that at a PCA3 Score cut-off of 35, 60% of initial biopsies could have been avoided while 11% of cancers with Gleason sum ≥ 7 would have been missed. A cut-off of 20 could still have avoided 40% of initial biopsies but would only have missed 2% of cancers with Gleason sum 7. A study by Deras also showed that the performance of PCA3 in 277 men undergoing an initial/first biopsy was comparable to that in 280 men undergoing a repeat biopsy [3].

The diagnostic accuracy for predicting initial biopsy outcome was found to be significantly better for the PCA3 Score (Area Under the Receiver Operating Characteristic Curve [AUC ROC] 0.761) than for total PSA (0.577), PSA density (PSAD; 0.689) and %free PSA (0.606). If a PCA3 Score cut-off 35 was included in a base multivariate model (including PCa risk factors age, DRE, serum total PSA, and prostate volume), it increased the diagnostic accuracy by up to 5.5% (from 0.737 to 0.792; P=0.03). The latter finding shows that PCA3 can be considered clinically meaningful for deciding on the usefulness of an initial prostate biopsy and justifies its application in clinical practice.

The study also provided further evidence that PCA3 Scores may be predictive of PCa aggressiveness. PCA3 Scores were significantly higher in men with a biopsy Gleason sum ≥ 7 than in those with a Gleason sum < 7 (median 72 vs 40; P<0.0001), in men with > 33% positive biopsy cores vs those with ≤ 33% positive cores (median 78.5 vs 39; P<0.0001), and in men with significant vs those with indolent PCa (median 57 vs 31; P=0.0016). Indolent PCa was defined as T1c, PSAD < 0.15 ng/mL, biopsy Gleason sum < 7 and ≤ 33% positive cores according to Epstein biopsy criteria. Although several previous studies have also shown an association between PCA3 Score and signs of PCa aggressiveness [4-7], others did not confirm these findings [1,3]. However, the latter negative studies did not use the PROGENSA PCA3 Assay .

Overall, the results of this study suggest that the PCA3 Assay can aid in the decision which men need an initial prostate biopsy, with a better diagnostic accuracy than total PSA, PSAD or %free PSA. In addition, they show that PCA3 Scores may be indicative for PCa significance and may therefore aid in the selection of men for whom active surveillance is a suitable treatment option.

References 1. Marks LS, Fradet Y, Deras IL, et al. Urology 2007;69:532-5. 2. Haese A, de la Taille A, Van Poppel H, et al. Eur Urol 2008;54:1081-8. 3. Deras IL, Aubin SM, Blase A, et al. J Urol 2008;179:1587-92. 4. Nakanishi H, Groskopf J, Fritsche HA, et al. J Urol 2008;179:1804-9. 5. Whitman EJ, Groskopf J, Ali A, et al. J Urol 2008;180:1975-8. 6. Aubin SMJ, Reid J, Sarno MJ, et al. J Urol 2010;184:1947-52. 7. Ploussard G, Durand X, Xylinas E, et al. Eur Urol 2011;59:422-9.

Written by:
de la Taille A, Irani J, Graefen M, Chun F, de Reijke T, Kil P, Gontero P, Mottaz A, and Haese A. as part of Beyond the Abstract on This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

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