The clinical relevance of new biomarkers is tricky


Assiduous readers of this blog will have noted that there are relatively frequent mentions of “new” biomarkers that may have potential as indicators of the aggressiveness of prostate cancer — but that in most cases those biomarkers are never heard of again.

The problem is that it is (relatively) easy to find new biomarkers (e.g., specific genetic material and  the downstream products of genetic material, including proteins and enzymes and other biological products) that are associated with early stage or progressive prostate cancer. It is much, much harder to show definitively that the presence or absence of such biomarkers is a clearly prognostic factor for a specific clinical or biological event in  the development or the progression prostate cancer from the first cell to the presence of castration-resistant disease. And even when the association seems very likely to have prognostic or evaluative significance, we still need to be able to prove it through some form of prospective study, even if we think we can demonstrate it in retrospective analyses.

An article developed by HealthDay that appears on the Businessweek web site today provides an excellent example of how this plays out in the real world. Dr. Concato and his colleagues at Yale have identified “[t]hree molecules associated with prostate cancer might provide the long-sought markers that could discern which tumors are life-threatening and need aggressive treatment.” (Their original article is published in full in the Annals of Internal Medicine.)

Dr. Concato is quoted as follows, “We’re not trying to say these are the only markers. … This is a proof of principle. … If the markers are positive, that might be an indication that more aggressive therapy is indicated.”

By contrast, in an accompanying editorial, Gelmann and Henshall have challenged the value of all three biomarkers. In their opinion, we don’t yet have enough information to know if the potential of these biomarkers can even be appropriately validated.

The truth is that we have to be able to appropriately validate new biomarkers. It doesn’t matter if Dr. Gelman or Dr. Concato is right in the present case. However, it might be a great deal better for everyone if there was less publicity given to the possibility that individual biomarkers had value and great deal more attention to proof of the possibility in each individual case!

At present, as we have pointed out before in this blog, there isn’t even any proof that PSA velocity is a better predictor of prostate cancer risk than an individual PSA level at a point in time. Many physicians act as though it is, but the truth is that we don’t know! If we aren’t able to prove this yet — with all of the accumulated data that we have on PSA velocity — how much more difficult do you think this may be for more specific forms of biomarker?

One Response

  1. I’ve gained a new focus on this kind of issue while reading Dr. Judah Folkman’s biography (a really good read incidentally) and how the media tend to leap on “good news” extracts from scientific papers that merely suggest that some piece of scientific investigation will prove to be the Holy Grail for a specific disease.

    Of course there is also sometimes a degree of manipulation of the media, especially where there is money involved — like share prices for example, but I believe that most of the breathless announcements of breakthroughs are merely a byproduct of the fact that all journalists face a blank sheet (or screen) every day and it has to be filled.

    On the other hand … it is truly difficult to get people to change their minds. As Galbraith said, “Faced with the choice between changing one’s mind and proving that there is no need to do so, almost everybody gets busy on the proof.”

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