Can Urinary PCA3 Supplement PSA in the Early Detection of Prostate Cancer?

Abstract

Purpose Given the limited sensitivity and specificity of prostate-specific antigen (PSA), its widespread use as a screening tool has raised concerns for the overdiagnosis of low-risk and the underdiagnosis of high-grade prostate cancer. To improve early-detection biopsy decisions, the National Cancer Institute conducted a prospective validation trial to assess the diagnostic performance of the prostate cancer antigen 3 (PCA3) urinary assay for the detection of prostate cancer among men screened with PSA. Patients and Methods In all, 859 men (mean age, 62 years) from 11 centers scheduled for a diagnostic prostate biopsy between December 2009 and June 2011 were enrolled. The primary outcomes were to assess whether PCA3 could improve the positive predictive value (PPV) for an initial biopsy (at a score > 60) and the negative predictive value (NPV) for a repeat biopsy (at a score < 20). Results For the detection of any cancer, PPV was 80% (95% CI, 72% to 86%) in the initial biopsy group, and NPV was 88% (95% CI, 81% to 93%) in the repeat biopsy group. The addition of PCA3 to individual risk estimation models (which included age, race/ethnicity, prior biopsy, PSA, and digital rectal examination) improved the stratification of cancer and of high-grade cancer. Conclusion These data independently support the role of PCA3 in reducing the burden of prostate biopsies among men undergoing a repeat prostate biopsy. For biopsy-naive patients, a high PCA3 score (> 60) significantly increases the probability that an initial prostate biopsy will identify cancer.

PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3

“…Notably, the most specific biomarker in human prostate cancer identified to date is an lncRNA, prostate cancer antigen 3 (PCA3, also known as PCA3 DD3 or DD3 PCA3 ), which is up-regulated in human prostate cancer (2). Since its discovery more than 15 y ago, PCA3 has been extensively investigated (3) and has been approved for clinical applications to aid the diagnosis of prostate cancer in both the European Union and the United States. Paradoxically-despite its striking clinical specificity-the inherent cellular role of the lncRNA PCA3 in human prostate cancer, if any, remains completely unknown (1).…”

Canadian Urological Association recommendations on prostate cancer screening and early diagnosis

“…In a prospective validation study conducted by the National Cancer Institute, the performance of PCA3 was assessed in 859 men that were enrolled from 11 centres. 87 In the biopsy-naive setting, there was a high rate of undiagnosed high-grade cancers (13%) using a PCA3 score <20, compared to 3% in the repeat setting.…”

Nuclear magnetic resonance spectroscopy as a new approach for improvement of early diagnosis and risk stratification of prostate cancer

“…PCA3 (prostate cancer gene 3) in urine is the only Food and Drug Administration (FDA)-approved urinary biomarker of clinical PCa, while the fusion gene TMPRSS2 ERG, α-formyl coenzyme A racemic enzyme (AMACR), single nucleotide polymorphism (SNP), and others have also been reported and confirmed to have correlations with PCa. Therefore, they could be rated as potential PCa biomarkers in urine and may find their way into clinical diagnosis and assessment of therapeutic efficacy (Prensner et al, 2012;Salagierski and Schalken, 2012;Salami et al, 2013;Shipitsin et al, 2014;Wei et al, 2014;Bansal et al, 2015;Frantzi et al, 2015). Recently, prostate born exosomes in urine-called prostasomes-have been used as a promising source of biomarkers (Ronquist and Brody, 1985;Duijvesz et al, 2011;Zijlstra and Stoorvogel, 2016).…”