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 Nov;184(5):1947-52. doi: 10.1016/j.juro.2010.06.098. Epub 2010 Sep 17.

Abstract

Purpose: We determined the performance of PCA3 alone and in the presence of other covariates as an indicator of contemporaneous and future prostate biopsy results in a population with previous negative biopsy and increased serum prostate specific antigen.

Materials and methods: Urine PCA3 scores were determined before year 2 and year 4 biopsies from patients in the placebo arm of the REDUCE trial, a prostate cancer risk reduction study evaluating men with moderately increased serum prostate specific antigen results and negative biopsy at baseline. PCA3, serum prostate specific antigen and percent free prostate specific antigen results were correlated with biopsy outcome via univariate logistic regression and ROC analyses. Multivariate logistic regression was also performed including these biomarkers together with prostate volume, age and family history.

Results: PCA3 scores were measurable from 1,072 of 1,140 subjects (94% informative rate). PCA3 scores were associated with positive biopsy rate (p <0.0001) and correlated with biopsy Gleason score (p = 0.0017). PCA3 AUC of 0.693 was greater than serum prostate specific antigen (0.612, p = 0.0077 vs PCA3). The multivariate logistic regression model yielded an AUC of 0.753 and exclusion of PCA3 from the model decreased AUC to 0.717 (p = 0.0009). PCA3 at year 2 was a significant predictor of year 4 biopsy outcome (AUC 0.634, p = 0.0002), whereas serum prostate specific antigen and free prostate specific antigen were not predictive (p = 0.3281 and 0.6782, respectively).

Conclusions: PCA3 clinical performance was validated in the largest repeat biopsy study to date. Increased PCA3 scores indicated increased risk of contemporaneous cancers and predicted future biopsy outcomes. Use of PCA3 in combination with serum prostate specific antigen and other risk factors significantly increased diagnostic accuracy.

Publication types

  • Validation Study

MeSH terms

  • Antigens, Neoplasm / urine*
  • Azasteroids / therapeutic use
  • Biopsy / statistics & numerical data
  • Controlled Clinical Trials as Topic
  • Dutasteride
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Male
  • Placebos
  • Predictive Value of Tests
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / urine*
  • Risk Factors

Substances

  • Antigens, Neoplasm
  • Azasteroids
  • Enzyme Inhibitors
  • Placebos
  • prostate cancer antigen 3, human
  • Dutasteride