Evaluation of the real utility of new biomarkers for prostate cancer risk

There is a fascinating comment by Kattan scheduled for publication in a forthcoming issue of the new journal Urology Practice. It makes a truly critical point about whether any of the new biomarkers are actually adding significantly to what we know about how to assess risk for prostate cancer.

In discussing a new paper on the value of the PCA3 test, Kattan writes,

What really becomes clear from this review is that it is almost impossible to define the value of any biomarker until we actually define what the goal of PCa assessment really is. In other words we will first need to reach agreement on what end point is necessary and feasible for prediction. If there were agreement on that (the preferred and feasible end point), it would be relatively straightforward to determine the potential value of any biomarker such as PCA3. We could simply examine whether a novel biomarker improves our ability to predict this agreed-on end point of interest by quantifying the incremental predictive accuracy that the biomarker delivers.

We are in complete agreement with Kattan in his assessment of the situation.  There is no consensus at all on what any of the markers currently used to assess risk for prostate cancer should actually do (i..e, the “preferred and feasible” endpoint).

It would be reasonable to think about this as follows:

  • Let’s say that a PSA test result of a certain value (say 4.0 ng/ml) is able to predict that a man undergoing a 12-core, systematic, TRUS-guided biopsy will be found to have at least one positive biopsy core containing Gleason 3 + 4 = 7 prostate cancer with a probability of 15 percent. (This is a guesstimate; we don’t know that to be true.)
  • Then a new and “better” test would have to be able to predict the likelihood of at least one positive biopsy core containing Gleason 3 + 4 = 7 prostate cancer with a higher probability (of say at least 20 percent).

But we have no idea what a PSA test can actually do with a high level of probability. We have no meaningful endpoint (either preferred or feasible). So how can we possibly know whether a PCA3 test of a phi test or a 4KScore test is any “better” than a PSA test?

The nice thing about researchers like Michael Kattan is that they have no problem asking questions that other people really don’t want to address!

The truth is that all a PSA test can tell us is that “something seems to be up” about a man’s prostate. And one should really only conclude that if the PSA test is similar on a repeated blood draw (unless there are other clear symptoms of a specific problem).

And since we can’t tell what a PSA test can tell us with accuracy, then how are we going to be able to know if anything else is actually any “better”?

4 Responses

  1. Perhaps PCA3 combined with PSA is better than either alone?

  2. Dear Sammy:

    I think Dr. Kattan’s point would be “better at what?”

  3. I suppose the goal is to find prostate cancers that will cause significant morbidity and mortality to the patient before he dies of something else.

    No answer for that yet.

  4. Sam: I think Dr. Kattan is looking for something a lot more scientifically specific, as I tried to outline in the original commentary above.

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