PCA3 density as a marker for prostate cancer risk?

Regular readers will be aware that a PSA density (i.e., PSA ÷ prostate volume) > 0.15 has been identified and characterized as a risk factor for clinically significant prostate cancer by researchers at Johns Hopkins.

The accuracy of PSA density as a risk factor for clinically significant disease has never been actually tested in any type of prospective clinical trial. However, a group of French researchers has now carried out a first study to assess whether PCA3 density may also have potential as a marker that might demonstrate risk for prostate cancer. By analogy to PSA density, PCA3 density is assessed as the urinary PCA3 score ÷ prostate volume.

Ruffion et al. obtained relevant data from a series of 595 consecutive patients scheduled for initial prostate biopsy. For all 595 patients, their data included PSA levels, PCA3 scores, and estimated prostate volume, all assessed prior to a prostate biopsy, thus allowing appropriate calculation of PSA density and PCA3 density levels.

The authors report the following results from their study:

  • PSA density performed better than absolute PSA level and PCA3 density performed better than absolute  PCA3 score as predictors of a positive biopsy result.
  • PCA3 density predicted a positive biopsy result with the highest specificity (76 percent) among the four biomarkets.
  • The best calculated cutoff for PCA3 density was 1.
  • The probability of a positive biopsy result was
    • 70  percent if a patient’s PCA3 density ≥ 1
    • 29  percent if a patient’s PCA3 density was < 1.
  • At a cutoff for PCA3 denity of 0.5,
    • Biopsies could have been avoided in up to 52  percent of patients without prostate cancer, but
    • 15  percent of all prostate cancers would have been missed
    • 10 percent of prostate cancers with a Gleason score ≥ 7 would have been missed.
  • PSA density was the best predictor of Gleason score at biopsy.
  • PCA3 density was the best predictor of the proportion of invaded cores.

Whether PCA3 density really has a significant role to play in determining whether an individual patient needs a biopsy or not can certainly not be determined on the basis of this study alone, but the concept of PCA3 density does offer us another tool to explore in the continuing attempt to find ways to discriminate with accuracy between men at risk for clinically significant (as opposed to clinically insignificant) prostate cancer.

One of the problems with the above study is that we have no clarity about what percentage of the patients evaluated in this series might have been up- or down-graded at the time of any subsequent surgery (if surgery was carried out). Thus, we have no way to evaluate the true accuracy of the risk predicted by PSA, PCA3, PSA density, or PCA3 density in this retrospective analysis.

4 Responses

  1. I’m not very familiar with the PCA3 test. Does it check for aggressiveness? Or is it like the PSA that really doesn’t tell you much about this.

  2. How well are doctors able to estimate prostate volume? Do they do this based on a DRE, or ultrasound?

  3. Jerry:

    At present, the only thing that the PCA3 test is approved for is to tell whether a man who has had at least one prior negative biopsy but other continuing indicators of risk (such as a rising PSA) whether a repeat biopsy would be a good idea. Thus, it is a little hard to tell exactly what PCA3 is measuring from a clinical perspective. In that sense it is more like a PSA test than a Gleason score (that is definitely association with risk for aggression).

  4. Doug:

    In most cases prostate volume can be assessed on the basis of an ultrasound image, but I would assume it can also be done on the basis of MRI images as well (and perhaps slightly more accurately).

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