PCA3 Materials & News

Durand X, Moutereau S, Xylinas E, de la Taille A. Expert Rev Mol Diagn 2011;11:137-44

• This paper reviews current knowledge on the diagnostic and prognostic value of Prostate CAncer gene 3 (PCA3). The Progensa^TM PCA3 Test has proven its clinical relevance and predictive abilities for prostate biopsy outcome and has established a place in the clinical decision process to repeat a biopsy after a first negative procedure. Its relevance for the prognosis of prostate cancer (PCa) aggressiveness needs to be confirmed.
• Low specificity of serum prostate specific antigen (PSA) for detection of PCa leads to many unnecessary prostate biopsies and overdiagnosis/overtreatment of indolent cancer. The PCA3 Assay was developed in response to the need for additional diagnostic tests to better select patients at risk of a positive prostate biopsy, as well as to provide prognostic information on the significance of PCa. PCA3 mRNA is highly expressed in prostate tumour but has a low expression in benign prostate tissue.
• The PCA3 Progensa^TM PCA3 Assay measures both PCA3 and PSA mRNA concentrations in urine samples taken after a digital rectal examination (DRE). The test has demonstrated good reproducibility with low intra- and inter-assay variability. The stability of the PCA3 mRNA and PSA mRNA and PSA in urine was shown to be at least 5 days at 2-8°C. A DRE of 3 strokes per prostate lobe yields informative rates of at least 94% (informative rate: % of urine samples providing sufficient mRNA for PCA3 analysis).
• Between 2003 and 2010, eight European and North-American prospective studies reported PCA3 test outcomes from patients scheduled for prostate biopsy (initial or repeat) because of elevated PSA and/or abnormal DRE. Test sensitivity ranged from 54 to 82%, specificity from 56.3 to 89%, positive predictive value from 66 to 89% and negative predictive value from 74 to 90%. Receiver Operating Curve (ROC) analyses showed higher positive and negative predictive values of the PCA3 Score over total and/or free PSA level, but slightly lower sensitivities. The performance of the PCA3 Score persisted regardless of the PSA level. There was no significant difference in diagnostic performance between initial and repeat biopsy groups.
• Recent preliminary results from a European study showed a good diagnostic performance of the PCA3 Score in patients with PSA Scores 3-10 ng/mL undergoing a first biopsy. Higher PCA3 Scores were associated with a higher probability of having a positive biopsy. A patient who initially had a PCA3 Score > 35 had a cumulative probability of 96% of having a positive biopsy after 3 series. In another study including men screened for the third, fourth or fifth time for PCa, the PCA3 test eliminated 52% of unnecessary biopsies and had a higher ROC area under the curve (AUC) than PSA (0.635 vs. 0.581).
• Two prospective, multi-centre studies in patients undergoing a repeat biopsy showed a correlation between PCA3 Score and the probability of a positive second biopsy. A PCA3 Score cut-off of 35 had a greater diagnostic accuracy than %free PSA (cut-off 25%). The PCA3 Score was independent of the number or previous biopsies, age, prostate volume and total PSA level. According to other studies in men with a previous negative biopsy, PCA3 is a better independent predictor of positive biopsies than %free PSA and men with a positive follow-up biopsy tend to have a higher PCA3 score. Adding PSA3 Score (threshold 17) to a decision-making tool increased the predictive value with 5%.
• Several studies have shown an association between PCA3 Score and PCa aggressiveness features of prostatectomy specimen, i.e. total tumour volume, postoperative tumour stage and Gleason score. These findings could not be reproduced when urine sediments were used instead of whole urine. Further studies are needed to confirm the prognostic value of the PCA3 score. The correlation between PCA3 Score and tumour size suggests the possibility for determining the potential aggressiveness of PCa in patients with a high PCA3 Score and stratifying patients according to tumour volume.
• Several studies have investigated the diagnostic performance of a combination of PCA3 and other gene fusion transcripts (e.g. TMPRSS2-ERG) or other mRNA biomarkers for PCa. Several of these combinations have been suggested to improve the diagnostic value, although more research is warranted.

More information: Article at PubMed