PCA3 Materials & News

Roobol MJ, Schröder FH, van Leeuwen P, Wolters T, van den Bergh RCN, van Leenders GJLH, Hessels D. Eur Urol 2010;58:475-81

• This analysis of the Rotterdam section of the European Randomised Study of Screening for Prostate Cancer (ERSPC) shows that the Prostate CAncer antigen 3 (PCA3) test has improved performance characteristics and better identifies significant prostate cancer (PCa) compared to prostate specific antigen (PSA) as a first-line screening test in 721 older men undergoing re-screening
• This analysis of the Rotterdam section of the ERSPC included 721 re-screened men aged 63-75 years, receiving a 6-core biopsy because they had either a serum PSA ≥ 3 ng/mL (N=492) or  a PCA3 Score ≥ 10 (N=32) or both (N=197). About 30% of men had a prior negative biopsy. Mean PSA level was 2.74 ng/mL and mean (median) PCA3 Score 51.9 (33.0) 
• The biopsy was positive for PCa in 16.9% of cases
• The PCA3 test showed improved performance characteristics and identification of significant PCa compared to serum PSA (Table)
• There was a trend for PCA3 to have a higher Area Under the Receiver Operating Characteristic (AUC ROC) curve vs. serum PSA in all men, men with a repeat biopsy and men with a PSA < 3.0 ng/mL; however, statistical significance was not reached
• In 492 men with a serum PSA < 3.0 ng/mL, a PCA3 Score of 35 and 20 would miss  4 (36%) and 0 of 11 significant PCa, respectively while avoiding 247 (50%) and 112 (23%)  unnecessary biopsies, respectively
• In 212 men with a repeat biopsy, a PCA3 Score of 35 and 20 would miss 0 and 0 of 3 significant PCa, respectively while avoiding 110 (52%) and 55 (26%) unnecessary biopsies, respectively
• It was discussed that the limitations of this study were that only a 6-core biopsy was performed potentially leading to missed cancers, and that the study was performed in pre-screened men potentially leading to selection bias (i.e. two-third of men had a PSA level < 3.0 ng/mL)
• It was concluded that the PCA3 test as a first-line screening test shows improvement of the performance characteristics and identification of significant PCa compared to serum PSA in this population of pre-screened men with a serum PSA ≥ 3.0 ng/mL

Editorial comment

This is the first time that the utility of PCA3 is studied in men that have been systematically pre-screened for prostate cancer at least twice. This information is crucial to provide a rationale for the indication(s) for the use of PCA3. As expected in this cohort, few men have significant cancer (n=19) which is quite different from what is seen in a typical population of men that undergo their first biopsy. Due to these low numbers, one has to be prudent in attempts to extrapolate the studies, yet there is a good indication that unlike for serum PSA  there is a safe threshold for PCA3.  Based on these findings and other reports by Haese (1) and de la Taille (2) a threshold for the PCA3 Score around 25 misses <10 % of significant cancers. This is considerably better than for serum PSA for which such a threshold cannot be defined and for which we know from the PCPT study that at a cut-off level of 3 ng/mL, 41% of significant cancers are missed. Considering that we are challenged to find biomarkers that reduce overdiagnosis, and improve underdiagnosis, PCA3 presents itself as a good candidate. Well designed studies based on PSA and PCA3 based algorithms, and ideally combined with methods to improve the prostate biopsies as diagnostic tools are likely to results in significant steps forward in the oncoming 5 years!

1) Haese A, de la TA, van PH, Marberger M, Stenzl A, Mulders PF, et al. Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur Urol 2008;54:1081-8.
2) de la Taille A, Irani J, Graefen M, et al. The PCA3 Assay improves the prediction of initial biopsy outcome and may be indicative of prostate cancer aggressiveness Eur Urol Suppl 2010:9:53 (abstract n.61).

More information: Article at PubMed