Next
Publication

Roobol MJ, Schröder FH, van Leenders GLJH, Hessels D, van den Bergh RCN, Wolters T, van Leeuwen PJ. Eur Urol 2010; in press (doi:10.1016/j.eururo.2010.09.030)

  • This analysis of the Rotterdam section of the ERSPC (European Randomised Study of Screening for Prostate Cancer) shows that the positive predictive value (PPV) of the PCA3 Assay in pre-screened men with a PCA3 Score ≥ 100 is comparable to that in other studies and averages 59%. The specificity of the PCA3 Assay in these men is reported to range between 89.7-95%
  • This analysis of the Rotterdam section of the ERSPC included pre-screened men (prostate specific antigen (PSA) ≥ 3 ng/mL) aged 63-75 years. In a prior analysis, 31% of men with a PCA3 Score ≥ 100 had a positive 6-core biopsy while specificity was 90%1. This analysis further evaluated the reproducibility and detection characteristics of the PCA3 Assay in men with a very high PCA3 Score. After a mean period of 19 months, repeat PCA3 testing was performed in men with a PCA3 Score ≥ 100 and < 100 and repeat biopsies (8-12 cores) were performed if PSA was ≥ 2.5 ng/mL and/or the PCA3 Score was ≥ 35
  • Retesting of original frozen PCA3 urine samples was performed to exclude possible analyses or processing errors at initial testing. PCA3 Scores < 100 were confirmed in 96.5% of 117 cases and PCA3 Scores ≥ 100 in 50.6% of 83 cases. This discrepancy was attributed to thawing of the frozen urine specimens causing gel formation which raised problems in obtaining adequate samples for the PCA3 Assay
  • In 20 men with a PCA3 Score ≥ 100 who had a repeat biopsy, prostate cancer was detected in 6 cases (30.0%). This was higher than in 16 men with a PCA3 Score < 100 in whom prostate cancer was detected in 3 cases (18.8%). Combining initial and repeat biopsy data resulted in a positive repeat biopsy rate of 52.2% in men with a PCA3 Score ≥ 100. It remains unknown why in 47% of men with high PCA3 Scores cancer was not detected. Possible explanations are presence of anterior prostate cancer or high-grade prostatic intraepithelial neoplasia (HGPIN). Longer follow-up of these men may provide more information. The specificity of the PCA3 Assay in men with PCA3 Scores ≥ 100 is reported to be high (89.7-95%)
  • Over a period of 19 months PSA levels and PCA3 Scores remained within ± 0.25% change in 64% and 41% of cases. The variation in PCA3 Scores could be due to thawing of frozen urine samples
  • It was concluded that the PPV of the PCA3 Assay in men with a PCA3 Score ≥ 100 in this study is comparable to that in other studies and averages 59%. There is still no good explanation why in some men PCA3 Scores are very high but biopsies are negative. Nevertheless, adding PCA3 to the decision to biopsy in men with PSA < 3.0 ng/mL, resulted in detecting 64% additional cases of PCa of which 15% could be considered as potentially life threatening if detected at a later stage.
  1. Roobol MJ, et al. Performance of the Prostate CAncer antigen 3 (PCA3) and prostate-specific antigen in prescreened men: exploring the value of PCA3 for a first-line diagnostic test. Eur Urol 2010;58:475-81

Editorial comment

This study showed that the PPV of the PCA3 Assay in men with a PCA3 Score ≥ 100 scheduled for a repeat biopsy is on average 50-60%. When looking at men scheduled for initial biopsy, the PPV of the PCA3 Assay has been reported to be 78%1.  The authors stated that there is no good explanation why in some men PCA3 Scores are very high but repeat biopsies are negative. It could be hypothesized that men undergoing repeat biopsy have a tumour on a site that is difficult to detect with a classic biopsy, for example an anterior tumour. It could also be suggested that the high PCA3 Scores are related to precancerous states, such as high-grade prostatic intraepithelial neoplasia (HGPIN), that may progress in the future. Indeed a recent analysis of the REDUCE study has shown that a high PCA3 Score was predictive of a positive biopsy outcome 2 years later2. This has also been suggested by a follow-up study of men with high PCA3 Scores but an initial negative biopsy3. The predictive value of high PCA3 Scores should be further evaluated in large-scale, long-term studies.  

  1. De la Taille A, et al. Clinical evaluation of the PROGENSA® PCA3 (Prostate CAncer gene 3) Assay in guiding initial biopsy decisions. J Urol 2011; in press
  2. 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
  3. Remzi M, et al. Follow-up of men with an elevated PCA3 score and a negative biopsy: does an elevated PCA3 score indeed predict the presence of prostate cancer? BJU Int 2010; 106:1138-42

More information: Article at PubMed

PCA3 is indicative of prostate cancer significance; pooled analysis of 2 multi-centre studies including 1,009 men