Publication

Shappell SB, Fulmer J, Arguello D, Wright BS, Oppenheimer JR, Putzi MJ. Urology 2008;73:363-8

  • This community-based study shows that the PCA3 test performs well in clinical practice with a high informative rate (98%), a strong agreement between laboratories (94%) and a high sensitivity (72.7%) and specificity (84.2%; PCA3 Score cut-off 35).
  • This US study evaluated the patterns of use of the PCA3 test by community urologists and determined the performance of the PCA3 test in a reference laboratory setting.
  • A total of 278 PCA3 tests were performed between December 2006 and June 2007. Of the men with available data in biopsy history, 55.5% had undergone > 1 prior biopsy. Of the men with available serum prostate specific antigen (PSA) levels, 80.6% had a PSA level 2.5-10 ng/mL.
  • The PCA3 test was very robust: the informative rate was 97.5% (informative rate: percentage of urine samples that contain sufficient PCA3 mRNA and PSA mRNA to determine the PCA3 Score). This implies that in clinical practice few men have to come back to repeat the PCA3 test.
  • The PCA3 test showed good inter-laboratory agreement: 47 of 50 (94%) PCA3 testing samples sent to 2 independent laboratories showed concordant results.
  • No correlation was found between the serum PSA level and the PCA3 Score (r=-0.0845) for patients with both a PCA3 Score and PSA level available (n=183).
  • In 35 men who had a reflex PCA3 test (i.e. a PCA3 urine sample was collected at biopsy), the mean PCA3 Score was higher in those with a positive biopsy compared to those with a negative biopsy (Figure; note: no statistical analysis was performed).
  • In 35 men who had a reflex PCA3 test, the PCA3 test had a sensitivity of 72.7% and specificity of 84.2% for detecting prostate cancer on biopsy (PCA3 Score cut-off 35).
  • A total of 32 men with a positive PCA3 test (PCA3 Score ≥ 35), of which 19 had had a prior biopsy, underwent a (repeat) biopsy. In 13 of these 32 men (41%) prostate cancer was detected; 11 (85%) of these tumours were considered to be clinically significant. 4 of 32 biopsies (12.5%) demonstrated HGPIN. 10 out of 19 men (53%) with a positive PCA3 test and a prior negative biopsy, had a positive repeat biopsy.
  • A total of 9 men with a negative PCA3 test (mean PCA3 Score 14.8) underwent a first biopsy, of which 4 (44%) were positive. However, two of these tumours (50%) were considered clinically insignificant (while this was the case in 15% of tumours found in patients with a positive PCA3 test).
  • It was concluded that the PCA3 test performs well in clinical practice, showing a high informative rate and a strong agreement between laboratories as well as a high sensitivity and specificity for detecting prostate cancer. In patients with a high PSA level and prior negative biopsies, the PCA3 test may be useful in choosing between a repeat biopsy and a more conservative follow-up.

Mean PCA3 Scores in benign tissue, HGPIN/ASAP and prostate cancer

Editorial comment

This study assesses the true clinical utility of PCA3 in a community based setting. Unlike, the first proof of principle paper on the potential value of urine PCA3 analysis, most studies reported deal with a selected academic population. The studies shows that in the community based population the PCA3 test performs very well. Interestingly, a positive PCA3 and a negative biopsy was often associated with a positive repeat biopsy, indicating that the positive predictive value (PPV) is higher when the follow up is taken into account. A positive PCA3 test indicates stringent follow up!

More information: Article at PubMed