Another investigational test may refine data on need for prostate biopsy

A newly published paper  in the Journal of Urology describes a multi-center, prospective study of the potential of the investigational, urine-based, ProCaM™ assay as a test to offer improved evaluation of the need for prostate biopsy among men with an initial total serum PSA level between 2 and 10 ng/ml.

The ProCaM™ assay has been developed to detect epigenetic modifications among three markers (GSTP1, RARβ2 and APC) that appear to be indicative of significant risk for prostate cancer. Baden et al. initially enrolled 704 men with and without cancer at 18 clinical sites in the continental USA. All patients were between 40 and 75 years of age, had a PSA level between 2 and 10 ng/ml, received a digital rectal examination (DRE) prior to providing a urine sample, and were subsequently given a TRUS-guided biopsy with 10 or more biopsy cores being removed.

The results of the study were as follows:

  • 320/704 men (45.5 percent) were cancer-positive on biopsy.
  • 384/704 men (54.5 percent) were cancer-negative on biopsy.
  • 189/704 men (26.8 percent) were excluded because of study protocol violations.
  • Therefore only 515/704 men proved to be eligible for data analysis.
    • 232/515 (45.1 percent) were cancer-positive on biopsy.
    • 283/515 (54.9 percent) were cancer-negative on biopsy.
  • Based on analysis of data from these 515 men
    • Assay sensitivity was 60 percent.
    • Assay specificity was 80 percent.
    • The predictive accuracy of the assay was higher than that of age, DRE, family history, PSA level, prior negative biopsy and prostate volume.
    • Standard risk factors plus the assay result improved overall predictive power.
    • A man with a positive ProCaM result was 7.7 times more likely to have high grade cancer than a man with a negative ProCaM result.
    • A positive ProCaM assay correlated with a positive biopsy result and with Gleason score.

Bladen et al. conclude that the ProCaM assay “has the potential to add value to the biopsy decision making process by improving current prostate cancer screening algorithms to more accurately identify men with prostate cancer.”

The authors are careful to note a variety of limitations to this study, and it is a little disturbing to note the high level of protocol violations in a study of this type. What is clear, however, is that this is yet another test that may well have the potential to limit the need for inappropriate biopsies among men who are otherwise healthy but have PSA levels in the range between 2 and 10 ng/ml.

It seems likely that additional data would be necessary to define with greater precision the risks and benefits of this test, and the authors identify some of the issues that need resolution in the full text of their article. The authors of the study are all on the staff of the developers of this test.

7 Responses

  1. Now all we need to do is to get Medicare and all other health insurers on board to cover the half-dozen or so “package” of pre-biopsy testing that “just might” come to a somewhat close conclusion that a biopsy would be merited. Let’s see: PSA test, DRE, PCA3, now ProCaM, and I just know I must have left a couple others out. Just test with them all and if the percentage of positives is sufficient (what, over 50%?). As the saying goes, likely to be accepted “when h..l freezes over.” Gives all the more reason to at least be satisfied with “what we have:” PSA and DRE. And as another saying goes, “Close enough for government work.”

  2. Great article. I have been looking for information on the ProCaM. It would be great to find a paper published by non-conflicted researchers on this topic.

  3. Is the Wikipedia article on sensitivity and specificity, what is meant by those terms in this context?

    Are there any accepted data on the sensitivity and specificity of 10+ core biopsies?

  4. Dave:

    Sensitivity and specificity are correctly defined in the Wikipedia article as far as I can tell. (I am not a statistician.)

    The sensitivity and specificity of prostate biopsy using anywhere between 6 and 20 biopsy cores have been studied many times over the years. There are numerous articles in the literature going back in time to the development of TRUS-guided biopsy procedures in the 1980s. It has been shown over and over again that biopsy is not a particularly specific or sensitive procedure for the accurate diagnosis of prostate cancer, and there are all sorts of reasons for this. It is most certainly true today that biopsies conducted under color Doppler ultrasound guidance or MRI guidance are much more likely to be accurate than the current “standard” 12-core biopsy carried out under black and white TRUS guidance. However, a whole bunch of factors affect the specificity and sensitivity of prostate biopsy, including the skill and experience of the physician carrying out the biopsy and the skill and experience of the pathologist who is looking at the biopsy specimens in order to make a diagnosis.

    Think about one of the simplest problems … If I find any amount of cancer tissue (down to a single cell) in a biopsy core, then I can say with 100% certainty (specificity) that you have cancer in your prostate. However, if I give you a 12-core biopsy and every core is negative, all I can tell you is that there was no sign of cancer in the biopsy cores I took … but I may have simply “missed” a growing tumor by a millimeter or two, or there may actually be a very small tumor in one of the biopsy cores that was too small for the pathologist to identify.

    And then there is the whole question of whether the cancer that is found is actually clinically significant (i.e., worth treating) or not.

    A biopsy is a crude test. We need much better tests if we are ever going to be able to tell and individual patient that either, “You have an early form of aggressive prostate cancer that we can cure if we treat you now” or “You have an evident but indolent form of prostate cancer that we can keep an eye on but we almost certainly will never need to treat because it is indolent and will never cause you any problem.”

  5. So, the sensitivity and specificity of ProCaM is (considerably) further crowded by the uncertain sensitivity and specificity of a biopsy.

  6. My 64-year-old husband had a PSA of 3.6 ng/ml 6 weeks before having a second PSA of 6.0 ng/ml. This was after the local urologist put him on medication similar to Avodart. My question, does he go to the “standing room only” urologist for a “general assembly line” biopsy? We live in Sedona, AZ, which is a small town. The Mayo Clinic is “out of network” for us since we live in the state. My husband just wants to get another PSA to see what it is now. What should we do?

  7. Dear Anne:

    PSA levels can vary a great deal — even from day to day — although it is odd that your husband’s PSA should have risen after he was put onto a drug like Avodart. (Do you mean finasteride?)

    Also, if you live in Sedona, can’t you go to The Mayo Clinic in Scottsdale? That’s in Arizona.

    Here’ s what I would do:

    (a) Get another PSA test done by the local doctor, but make sure no sex and no bike riding or similar for 48 hours befcore the blood draw. They can both elevate PSA levels.

    (b) If you feel uncomfortable with the local urologist in Sedona, find out whether you could get the biopsy done either at The Mayo Clinic in Scottsdale or whether there is a good urologic oncology practice up in Flagstaff.

    (c) If the repeat PSA result is still 5 to 6 ng/ml or higher, it’s time for the biopsy, but get it done by someone who is really good at this.

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