The newly available, urine-based ExoDx Prostate(IntelliScore) test

Back in April this year we reported on the publication of an article in JAMA Oncology that gave information about the development of a new test for risk of clinically significant prostate cancer — a test that could be conducted using a simple urine sample.

The original paper was by McKiernan et al. and our prior report on that paper can be found if you click here.

We have now learned (from the company that developed this test and provides it) that the test described in the original paper and in our report — the ExoDx Prostate(IntelliScore) test, from Exosome Diagnostics — is now formally available. The company issued this media release about the availability of the test on September 7. Additional information about the test for patients (and also for physicians) can be found on the company’s web site.

According to Exosome Diagnostics,

ExoDx® Prostate(IntelliScore) is a non-invasive urine-based test designed to be used along with PSA and other standard of care factors (including age, race and family history) to enable physicians to predict whether a patient presenting for an initial biopsy does not have high-grade prostate cancer and, thus, could potentially avoid an initial biopsy and, instead, continue to be monitored.

If the test can perform as suggested by the company, then it may well have value in assessing whether or not individual patients really do need to have an immediate prostate biopsy. However, we suspect that many clinicians will want to see more data from more studies before they will feel able to rely on a test like this in managing risk for prostate cancer.

According to data provided by the company, the test is intended for men of ≥ 50 years of age with a PSA level of between 2 and 10 ng/ml. Basically, the lower the ExoDx® Prostate(IntelliScore), then the lower probability for high-grade disease on an initial biopsy. A cut-point score of 15.6 correlates with a 34 percent specificity for a negative prostate biopsy. This cut-point was optimized to increase the probability of finding clinically (more) significant high-grade disease, so a percentage of men with low-grade and benign biopsies will have false positive results using this test. In other words, the test is structured to err on the side of finding at least some prostate cancer that is lower in risk so as to optimize the chances that it will find high-risk prostate cancer.

The other place that a test like this may have future potential is in the regular monitoring of men on active surveillance. If this test shows no indication of risk for higher-grade prostate cancer in a man who is on active surveillance for low-risk prostate cancer, then it is possible that follow-up biopsies may not be necessary. However, again, more data may be needed to substantiate this possibility. We understand that the company is already in discussions with clinical research groups about testing the utility of this new test in this setting.

The great advantage of this test is that it is based on a simple urine sample as opposed to a blood sample or a biopsy. Consequently, the safety of the test is undoubtedly high. Unlike the PCA3 test, it doesn’t even require a vigorous digital rectal exam prior to collection of the urine sample.

The downside of this test is that it is exclusively available from the manufacturer though a CLIA-approved laboratory. Therefore, it has not been approved or evaluated by the US Food and Drug Administration — and nor does it have to be. However, this does mean that there has been no independent evaluation of the test’s accuracy by any type of regulatory agency. That may affect coverage of the costs for this test by at least some insurance providers.

What we can say for certain is that this is indeed the first available test that appears to be able to give highly specific information about the possibility that a man with a low but elevated PSA level or other possible signs and symptoms that might be associated with prostate cancer is at risk for clinically significant prostate cancer or not. Uptake of this test by urologists and other physicians over the next couple of years — and additional published data — are likely to be crucial to knowing just how well this test can perform in the “real world” of clinical medicine in lowering the need for prostate biopsies.

14 Responses

  1. Since it will almost certainly not be approved by Medicare or insurance, the cost of $595 becomes a crucial issue. That is especially true if anyone were to use it for monitoring while on active surveillance. I’m not even sure it can be used for continual monitoring — if it is giving a genetic profile of one’s type of prostate cancer, what do we know about whether those genomic elements change over time? That is, does this “3 gene signature” of the cancer progress as the cancer progresses, or does it just describe a time-invariant characteristic of that particular cancer?

    At $595, it is about $100 more than the 4Kscore, and about $400 more than PHI (which is FDA approved and covered by insurance and Medicare). Yet, all three of these tests have about the same accuracy (AUC of 0.73, 0.72 and 0.71 for predicting a Gleason score of ≥ 7 for EPI, 4Kscore, and PHI, respectively). Based on the information provided, they all seem to be similar in their sensitivity/specificity trade-offs. Ideally, we want a test with both good sensitivity and specificity at a given cutpoint. I agree that this requires more validation too.

  2. Where does the free PSA test fit in this scenario?

  3. Dear John:

    The role of the %free PSA test value has long been able to “suggest the possibility” that a man might be more likley to have prostate cancer if this percentage was very low (i.e., 25%), but the specificity of this test in defining who would or would not be found to have prostate cancer on biopsy has never been particularly high.

  4. John:

    Free PSA is one of the three kinds of PSA used in PHI and one of the four kinds in the 4Kscore (“K” stands for kallikrein, which is a family of proteins that includes PSA). Using several kinds of PSA has greater specificity than using just one (PSA) or two (% free PSA).

  5. This is not the first urine-based test to detect whether or not prostate cancer is aggressive. The miProstate Score index test has been available from the University of Michigan for over a year, and is highly reliable.

  6. Dear Ms. Hunt:

    Thank you for letting us know about this test. Apparently (according to a media release issued by the University of Michigan), the Mi-Prostate Score-associated test has been available since September 2013. I cannot comment on it’s accuracy since I haven’t seen data to support this. I must also point out that this is the first time I have ever seen any data about this test or had it brought to my attention by anyone, which does make me wonder just how widely it has been being used.

    Apparently to obtain an Mi-Prostate Score, one must combine data from the urine test (which gives data on PCA3 levels and on the presence of the T2:ERG genetic marker) with PSA data. Since one must get a PCA3 level, it is my assumption that the patient therefore needs a “vigorous” DRE prior to giving a urine specimen, and I have to say that I have found all PCA3 data to date to be unreliable at best.

  7. Hello, everyone.

    I would appreciate your input on my ExoDx urine test data. They showed a score of 26% which is above cut point of 15.6%. Should I be concerned? My recent PSA was 3.6 comparing to 2.6 a year ago. I am 67 years old.

  8. Dear Mark:

    That is a conversation that you really need to have with your urologist. However, the combination of a rise in PSA level from 2.6 to 3.6 and an ExoDx score of 26% do indicate a significant potential risk for a diagnosis with prostate cancer that might be clinically significant.

  9. Dear Mark Ioffe:

    I’ve recently had a similar ExoDx score result and would like to compare notes. If you are willing, please e=mail or call me as indicated below.


  10. I need to understand this better. I have had a consistent PSA of 1.7 over the past 10 years. I am now 61 years old and I had a PCA3 test 7 years ago which was 2. Now my doctor did this new test on me and it came in at 24. I don’t think he was that well versed in this test though. DRE showed calcification and increased prostate size over 7 years from 36 to 72 g. What does all this mean???

  11. Dear Mr. Warner:

    Your doctor appears to have a talent for trying out relatively new tests of unproven value on his patients (or at least on you). I don’t think the results of either of these two tests (the PCA3 test or the ExoDx test) can be relied on to tell us anything of any great importance (as yet), and most people think that the PCA3 test has “come and gone” in the sense that the results of that test have been shown to have high levels of false negatives and false positives.

    If I was wearing your shoes, I would be much more interested in having data from the older and simpler %PSA test (which can help to discriminate between risk for prostate cancer and risk for benign prostatic hyperplasia); from the Prostate Health Index or phi test; or from from the 4KScore test. The latter two tests can also provide reasonably reliable information about whether men do or don’t need a biopsy for risk of prostate cancer.

    I am also uncertain how a DRE can be used definitively to diagnose areas of calcification in the prostate (prostate “stones”).

    On the other hand, if your prostate mass has risen from 36 to 72 g over the past 7 years and your PSA level has been stable, it doesn’t seem very likely to me that you have prostate cancer. Perhaps what you really need is a different urologist?

  12. Mr Warner:

    I further note that your PSA level is below the level for which the developer of this test suggests that it is useful (men with a PSA level of at least 2.0 ng/ml). This would seem to be one more reason why you might want to consider getting a second (different) opinion on your risk for any type of prostate disorder.

  13. My PSA was relatively stable, hovering around 2.x while the prostate was enlarged. This was for about 5+ years. About 2 years ago (age 61) the PSA started climbing, to 3.x, then 4.x then into the 5.x range. This climb also coincided with having to take care of my wife, who had major back surgery and I still working full time. Increased stress? Oh my, yes.

    The urologist first did an ultrasound. A few months later he performed a biopsy, 14 samples, that, if I remember correctly, did not indicate cancer. I failed to ask about the Gleason score. The PSA since then has dropped a bit to the low 5.x range and has stayed there for the past year. Judging by the prostate size, he feels the PSA should be around 9.

    Two weeks ago we did the ExoDx test. (I had to sign a paper that I would pay the $795 cost if BCBS did not cover, which I have high confidence they will not.) The score was 20.58.

    He also wants me to get a MRI using the latest Siemens 3T Tesla machine. The results can be mapped onto the previous ultrasound. This mapping lets him see if the 14 sample sites did not miss an area that should be sampled.

    Considering all of the above, I put off the MRI until I can have a discussion on all the previous historical PSA values, the ultrasound, the samples, the Gleason score and the ExoDx.

    With all the legal wording I read on this test, just how much “weight” does it have within all the other test information? Might it be enough extra information to decide to put off the MRI and stick with monitoring the now stable, and unexpectedly low, PSA levels?

  14. Dear Martin:

    It is impossible to say what the level of relevance of the ExoDx test result might be relevant to the other tests you have had done to date.

    The one thing that I think I can say with a high degree of certainty is that your previous biopsy was negative for cancer. Just ask the urologist for a copy of the pathology report to confirm that.

    Might it be found that you have some cancer if you had an MRI carried out followed by an MRI/TRUS fusion-guided biopsy. Sure it might. You are 61 years of age, so there is a roughly 60% chance that you have at least a small amount of prostate cancer somewhere in your prostate. However, the real question is whether that risk is clinically significant. If your PSA has decreased form the highest levels it had reached previously, it would seem unlikley that you could have a clinically significant forms (or amount) of prostate cancer (although you probably do have an enlarged prostate, which is very common for a man in his 60s).

    What you want to do about this — if anything — is a matter for you and your doctors to discuss. The only known way to resolve that question with a high degree of accuracy is to have the MRI and then the MRI/TRUS-guided biopsy. My bet would be that you may well have a small focus of low-risk or very low-risk prostate cancer, but if you do it is probably not something that needs to be treated (at least at thsi time).

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