PCA3 Materials & News

van Poppel H, Haese A, Graefen M, de la Taille A, Irani J, de Reijke T, Remzi M, Marberger M. BJU Int 2012;109:360-6.

• This analysis of data from 2 multi-centre European studies enrolling 1,009 men shows that the PCA3 Score is associated with many biopsy and pathological features of insignificant or indolent prostate cancer (PCa), including biopsy and pathological Gleason score, clinical and pathological stage, % of positive biopsy cores and biopsy Epstein criteria
• This pooled analysis included data from 2 multi-centre European prospective trials evaluating the clinical utility of the PCA3 Assay in guiding initial¹ or repeat biopsy² decisions
• Of the 1,009 men enrolled, 348 (34%) had a positive biopsy
• The median and mean PCA3 Scores were statistically significantly lower in men with biopsy Gleason score < 7 vs. ≥ 7, with clinical stage T1c vs. T2-T2c, T3a cancers, with ≤ 33% vs. > 33% positive biopsy cores and with ‘biopsy indolent’ vs. ‘biopsy significant’ PCa (Figure 1; ‘biopsy indolent PCa’ defined according to Epstein criteria: T1c, PSA density < 0.15 ng/mL, biopsy Gleason score ≤ 6 and % positive cores ≤ 33%) 
• A total of 175 men with a positive biopsy underwent radical prostatectomy. Median and mean PCA3 Scores were statistically significantly lower in men with pathological Gleason score < 7 vs. ≥ 7, and with pathological stage T2a-T2c vs. T3a-T3b cancers (Figure 2)
• In men with a positive biopsy, the PCA3 Score had a statistically significantly higher diagnostic accuracy for predicting the presence of ≤ 33% positive cores than total PSA (P=0.005) and % free PSA (P=0.028). The percentage of positive cores in the biopsy is assumed to be a proxy for tumour volume
• It was discussed that several other studies have also shown a relationship between prostate cancer significance and the PCA3 Score^3,4,5. When compiling data from these studies and this pooled analysis it seems that there is increasing evidence that the PCA3 Score is indicative of PCa significance
• Treatment selection should be based on a combination of clinical and pathological variables to which the PCA3 Score may be added. When comparing across studies, the median PCA3 Score in men with ‘indolent’ PCa was about 20 and the median PCA3 Score in men with ‘significant’ PCa was about 50. It can therefore be suggested that a PCA3 Score ≤ 20 may identify patients with indolent PCa in whom active surveillance may be appropriate. A PCA3 Score threshold of 50 may be used to identify men at high risk of harbouring significant PCa who may be candidates for active therapy
• It was concluded that, although the association between the PCA3 Score and PCa aggressiveness needs further evaluation, the inclusion of PCA3 into management strategies may provide physicians with another tool to more accurately determine the course of treatment    

1) de la Taille A, et al. Clinical evaluation of the PCA3 assay in guiding initial biopsy decisions. J Urol 2011;185:2119-25
2) Haese A, et al. Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur Urol 2008;54:1081-8
3) Aubin SM, et al. PCA3 molecular urine test for predicting repeat prostate biopsy outcome in populations at risk: validation in the placebo arm of the dutasteride REDUCE trial. J Urol 2010;184:1947-52
4) Nakanishi H, et al. PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance. Urology 2008;179:1804-9
5) Whitman EJ, et al. PCA3 score before radical prostatectomy predicts extracapsular extension and tumor volume. J Urol 2008;180:1975-8

Figure 1. Median PCA3 Scores were statistically significantly lower in men with features of biopsy indolent PCa

Figure 2. Median PCA3 Scores were statistically significantly lower in men with pathological Gleason score < 7 vs. ≥ 7, and with pathological stage T2a-T2c vs. T3a-T3b cancers

Editorial comment

In this manuscript two studies are combined in which the urinary PCA3 test was evaluated. The study comes to a carefully formulated recommendation that PCA3 can be particularly helpful to aid in the decision to omit a biopsy at low values (<20), where the NPV is highest. The significant PPV especially for high risk cancers at the higher end of the scale (>50) prompts careful consideration of the possibility that a patients has high risk prostate cancer even when a previous biopsy was negative.

More information:
Abstract on PubMed