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Nyberg M, Ulmert D, Lindgren A, Lindström U, Abrahamsson P-A, Bjartell A. Scand J Urol Nephrol 2010;44:378-83

  • This small study in 62 men scheduled for first or repeat biopsy because of elevated prostate specific antigen (PSA) levels or suspicious digital rectal examination (DRE) confirms that PCA3 is a diagnostic marker for prostate cancer
  • A total of 62 men scheduled for first (55%) or repeat biopsy (45%) with a median total PSA level of 7.9 ng/mL were included. The time between PCA3 testing and PSA assessment was 0-92 days
  • The informative rate for the ProgensaTM PCA3 Assay was 100% demonstrating that all urine samples contained sufficient PCA3 and PSA mRNA for analysis
  • The positive (repeat) biopsy rate was 29%
  • The median PCA3 Score was statistically significantly higher in men with a positive biopsy (49; range 24-103) vs. those with a negative biopsy (22; range 14-42; P=0.003)
  • The probability of a positive biopsy increased with increasing PCA3 Scores
  • The risk of a positive biopsy increased by 2.6% with every one-step increase in PCA3 Score
  • A logistic regression model predicting biopsy outcome combining PCA3 and PSA did not show an improvement to either PCA3 or PSA alone. Receiver operating characteristic curve (ROC) analysis showed an area under the curve (AUC) of 0.74 for PCA3, 0.80 for total PSA and 0.82 for PCA3 and PSA combined, with the differences not being statistically significant
  • No correlation was found between PCA3 and prostate volume nor between PSA and prostate volume
  • It was discussed that it was surprising that the logistic regression model predicting biopsy outcome combining PCA3 and PSA did not show an improvement to either PCA3 or PSA alone as PCA3 and PSA are independent markers for prostate cancer. In addition, it is strange that no correlation between PSA and prostate volume was found as this correlation has been shown in many previous studies. Furthermore, previous studies evaluating the performance of the PCA3 Assay have consistently shown an improved diagnostic accuracy for PCA3 compared to PSA, which was not confirmed in this study. The authors explain this by the lack of inclusion criteria for either PSA or biopsy in this study. The small sample size may also have played a role
  • It was concluded that this study confirms that PCA3 is a diagnostic marker for prostate cancer. However, in this small set of patients with first and repeat biopsies, the PCA3 test does not fulfil the requirements for a new diagnostic marker to replace or complement PSA

Editorial comment

The authors of this study conclude that the PCA3 test does not fulfil the requirements for a new diagnostic marker to replace or complement PSA as PCA3 and serum total PSA performed equally well as diagnostic markers and a combination of PSA and PCA3 did not improve the diagnostic accuracy. However, as this study only included 62 men scheduled for a first or repeat prostate biopsy (median PSA level 7.9 ng/mL), the results should be regarded with caution. In a study including 570 men scheduled for a first or repeat biopsy (median PSA level 5.6 ng/mL), the ROC AUC for PCA3 was higher for PCA3 compared to serum PSA1. Prior large scale studies in men scheduled for a repeat biopsy (median PSA level 6.1-6.7 ng/mL) have also shown a statistically significantly better diagnostic accuracy for PCA3 compared to PSA or %free PSA2,3. In a recent analysis of the REDUCE study in 1,140 placebo-treated patients (serum PSA > 2.5 ng/mL), the diagnostic accuracy (ROC AUC) of the PCA3 Score for predicting a positive repeat biopsy was also statistically significantly higher for PCA3  vs. total PSA4. Also in 516 men scheduled for a first biopsy (median PSA level 5.5 ng/mL) ROC analysis showed a significantly higher AUC for the PCA3 Score vs. tPSA, PSA density and %free PSA5. A recent evaluation of two risk calculators/nomograms have also confirmed the additive value of the PCA3 Assay in predicting biopsy outcome5.
Therefore, it is indeed surprising that the logistic regression model predicting biopsy outcome combining PCA3 and PSA did not show an improvement to either PCA3 or PSA alone as PCA3 and PSA are independent markers for prostate cancer and several other studies have shown an increase in predictive accuracy when PCA3 and other risk factors for prostate cancer such as PSA were combined2,4,5,6,7. As this study also failed to show a correction between PSA and prostate volume, which has been demonstrated in many studies, the sample size may have been to small to evaluate these outcomes and come to such conclusion.From this small study in 62 men scheduled for first or repeat biopsy it can be concluded that PCA3 is predictive of biopsy outcome.

  1. Deras IL, et al. PCA3: a molecular urine assay for predicting prostate biopsy outcome. J Urol 2008;179:1587-92
  2. Haese A, et al. Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur Urol 2008;54:1081-8 
  3. Marks LS, et al. PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy. Urology 2007;69:532-5
  4. Aubin SM, et al. 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;184:1947-52
  5. Perdona S, et al. Prostate cancer detection in the “grey area” of prostate specific antigen below 10 ng/mL: head to head comparison of the updated PCPT calculator and Chun’s nomogram, two risk estimators incorporating prostate cancer antigen 3. Eur Urol 2010; in press: doi: 10.1016/j.eururo.2010.09.036.
  6. de la Taille A, et al.. The PCA3 Assay improves the prediction of initial biopsy outcome and may be indicative of prostate cancer aggressiveness. J Urol 2011; in press
  7. Chun FK, et al. Prostate cancer gene 3 (PCA3): development and internal validation of a novel biopsy nomogram Eur Urol 2009;56:659-67

More information: Article at PubMed

PCA3 is indicative of prostate cancer significance; pooled analysis of 2 multi-centre studies including 1,009 men