The practical clinical value of the PCA3 test

The prostate cancer gene 3 or PCA3 test has been commercially approved in Europe as a test that provides relevant information associated with the need for a prostate biopsy. It is still awaiting approval in the USA. The commercial name of this test in Europe is the PROGENSA® PCA3 assay. Various forms of PCA3 test can already be ordered in the USA from specialized laboratories.

Since the initial European approval, there have been a number of papers that have suggested that the PCA3 test may have little value in the “real world” outside of formal clinical trials. A new study by de la Taille et al. comes to a rather different conclusion.

de la Taille and colleagues set out to conduct an open-label, investigator-driven, prospective, multinational, multi-center, real-life study of the use of the PROGENSA PCA3 assay in actual clinical practice. While recruitment and assessment of patients was conducted according to a well defined protocol, the protocol could be adjusted based on the standards of care at the eight participating clinical centers. Between February 2008 and August 2009, the eight centers enrolled men with a total PSA of between 2.5 and 10 ng/ml and/or a suspicious DRE scheduled for initial biopsy. All participating patients had blood drawn for a total PSA test and provided urine for a PCA3 test (after a prostate massage); a %free PSA test was carried out on some but not all patients. All patinets then received a prostate biopsy with an average (median) of 12 cores per patient.

Here are the key findings of the study:

  • A total of 528 men were included in the study.
    • 516/528 (97.7 percent) were considered to be evaluable for PCA3.
    • 513/528 (97.2 percent) provided evaluable biopsy data.
    • 99 percent of the patients provided urine samples with sufficient PCA3 and PSA mRNA to allow calculation of their PCA3 scores.
    • 207/213 (40.4 percent) had a clearly positive biopsy result.
  • Higher PCA3 scores corresponded with a higher probability of a positive biopsy.
  • The average PCA3 score was higher for men with positive biopsy results compared to negative biopsy results.
    • Mean: 69.6 vs 31.0.
    • Median: 50 vs 18.
  • PCA3 scores were independent of age, total PSA level, and prostate volume.
  • The PCA3 score (at a cutoff of 35) had a sensitivity of 64 percent and a specificity of 76 percent.
  • The PCA3 score was significantly higher in
    • Men with biopsy Gleason score of ≥ 7 compared with men with a Gleason score of < 7
    • Men with > 33 percent positive biopsy cores compared to ≤ 33 percent positive cores
    • Men with clinically significant compared with indolent disease
  • Inclusion of PCA3 data in prognostic models (e.g., the PCPT prostate cancer calculator) increased their predictive accuracy by up to 5.5 percent.

The authors also calculate that:

  • At a PCA3 score cutoff of 35,
    • 309 biopsies (60 percent) could have been avoided.
    • 22 cancers with a Gleason score of ≥ 7 would have been missed.
  • At a PCA3 score cutoff of 20,
    • 205 biopsies (40 percent) could have been avoided
    • 5 cancers with a Gleason score of 7 would have been missed.

Based on the data from this study, it would seem reasonable to give every man with a total PSA of between 2.5 and 10 ng/ml a PCA3 test before they wedre given a biopsy. At worst, it would appear that the cost of giving the PCA3 test would be offset by the money saved by not giving biopsies to men with a PCA3 of < 20 (assuming that there was no other clear signal that a biopsy was warranted, such as a clearly positive DRE). Having said that, it also seems likely that some additional studies may be needed before appropriate protocols for use of the PCA3 test are finalized in both Europe and the USA.

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