Understanding new tests for risk of clinically significant prostate cancer

Over the next few years we are going to see the development and marketing of a plethora of new tests related to the diagnosis and prognosis of prostate cancer. Some of these tests may have high utility and value. Others are likely to have a much lower value (but still see high use). As an example, let’s look at the (relatively new) Confirm MDx for Prostate Cancer test.

The Confirm MDx for Prostate Cancer test (which we’ll call CMDxPC) is developed and marketed by MDx Health and is solely available though MDx Health’s approved clinical laboratories. Provision of the test in this manner does not require FDA approval. The doctor simply sends specified pathology slides or other specimens to MDxHealth.

Like the PCA3 test, CMDxPC is designed to help to better identify men who have a negative result on an initial, systematic prostate biopsy, but who the doctor (or perhaps the patient himself) has a high concern that the negative biopsy result is not actually correct.  It is certainly the case that some 20 to 25 percent of men who have an initial negative biopsy for suspicion of prostate cancer will turn out to have prostate cancer if they are given a sufficient number of re-biopsies. Thus CMDxPC was designed to help urologists identify which of their patients really don’t need unnecessary repeat biopsies (because they have a very high probability of really not having prostate cancer at all) and those patients who really do require repeat biopsies (and potential treatment) because they have a high probability for a positive re-biopsy result.

How does CMDxPC work? Well, that’s kinda complicated, but basically it investigates the methylation levels of three genes that are known to be associated with heightened risk for prostate cancer when present and methylated.

We now have data from two studies of the application of CMDxPC. The results of these two studies have also been discussed in an article on the Medscape Oncology web site.

The first of these studies is the so-called MATLOC study, and the results of this study have just been published by Stewart et al. in the Journal of Urology. The MATLOC study used archived biopsy tissue samples from 483 patients in the UK and Belgium who had initially had negative biopsy results, and who and then had either positive results (cases, n = 87) or negative results (controls, n = 396) on re-biopsy within 30 months.

Interpreting the results of this paper is complex, but let’s see if we can give you the basics:

  • Of the 87 men who had a positive re-biopsy (before use of the CMDxPC), 56 had a Gleason score of ≤ 6; 22 had a Gleason score of 7; and just 7 had a Gleason score of 8-10.
  • The sensitivity of the CMDxPC test in accurately identifying the 87 men who had a positive biopsy core on re-biopsy was 68 percent, and the specificity was just 64 percent.
  • The test was 100 percent accurate in identifying those men who had a positive biopsy core on re-biopsy with a Gleason score of 8-10.
  • DNA methylation based on this test was an independent and significant risk factor for prostate cancer detection at up to 30 months before a re-biopsy.
  • Use of this test would definitely allow for a significant reduction in the number of repeat biopsies (but at a relatively low level of accuracy as defined by the sensitivity and specificity of the test).

The test — as used in this study –presents us with a problem. Why?

  • It can certainly be used to reduce the need to re-biopsy patients at low risk for a positive biopsy (but it is going to “miss” some of those men who might really benefit from a re-biopsy because they have Gleason 7 disease).
  • It will help us to identify many men with negative first biopsies who would have positive second biopsies with a Gleason score of 7 or less (but it doesn’t tell us what percentage of these men have clinically significant prostate cancer).
  • We are not told how many of the controls were identified as being at risk for prostate cancer according to the CMDxPC test despite two negative biopsies.

This test is most certainly a novel test, and it may have utility in the hands of some experienced physicians. However, it also may not represent any major breakthrough. We can see value for it in the management of some men who had poor experiences on a first biopsy and who are reluctant to undergo a second unless absolutely necessary, but then the low selectivity and specificity concern us.

A second study, presented by Gaston et al. just last week at the Genitourinary Cancers Symposium in Orlando, was based CMDxPC assassment of biopsy materials from just 76 patients. Gaston and her colleagues report that, in this study, evidence of gene promoter methylation seemed to be more prevalent in histologically benign cores from biopsy patients diagnosed with Gleason 7 disease than it was in biopsy cores from men with low-volume Gleason 6.

It seems to me that other tests in development may be able to offer us greater benefit than the CMDxPC. On the other hand, in the short term, we can see some doctors and their patients wanting to try this test. However, what we really need is something a lot more accurate, and preferably one that can be used before even a first biopsy!

We should add that we have no idea what this test costs or whether it is currently covered by Medicare or by commercial insurance companies.

2 Responses

  1. Myriad Genetics has a similar test under development. It will probably use some variation of the gene expression profile used in the Prolaris test they are currently bringing to market. The idea is to test tissue collected during a “negative” biopsy for the presence of biomarkers that would indicate that cancer actually was present, but the needle missed it. (Or, to verify that no cancer is present.) From a marketing perspective, I’m sure Myriad would suggest that all biopsy samples, positive or negative, could benefit from testing by Myriad. Genomic Health is bringing a test similar to Prolaris to market, and I imagine they will also develop (or are developing) a similar test for negative biopsies. (For positive biopsies, Prolaris is supposed to characterize the aggressiveness of the cancer).

    I am glad these tests are becoming available. If I had a positive biopsy I would want the Prolaris test results as part of the information to consider before deciding on treatment. Even if I had to pay the $3,500 out of pocket. (I’m not wealthy … spending $3,500 on this would require that I not do something else … maybe forgo a vacation, keep a 12-year-old car another year, etc.)
    I have been biopsied (no fun). Knowing what I know now, I would not have had this done based on my 3.8 PSA score alone. Unless something odd was detected during a DRE, or something showed up on an MRI image, I think that was an unnecessary biopsy.

  2. I agree with Mr. Miller. I would never subject myself to a biopsy without some indication on my DRE, a PCA3 test, or an MRI indicating that that something was unusual. If I did get a biopsy, I would definitely add [a genomic test like] the MDx test to the list. If the DRE, PCA3, and MRI don’t indicate [risk for] cancer, it seems like a biopsy is unjustified.

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