The real clinical utility of tests like Prolaris and Oncotype DX in management of prostate cancer

Regular readers (and others) who are interested in gaining more understanding of the potential clinical utility of the new, gene-based prognostic tests for the management of localized prostate cancer will be interested in reading a new article on the Medscape Oncology web site.

This article covers a presentation at ASCO — given by Jack M. Cuzick, PhD, of Queen Mary College University of London — on the potential of the Prolaris test (developed by Myriad Genetics) as well as the follow-up discussion following the presentation. (Click here for the original abstract of Dr. Cuzick’s ASCO presentation.) It also addresses similar issues discussed by your correspondent when talking to representatives of Genomic Health at the meeting regarding their Oncotype DX test.

We don’t wish to give anyone the impression that these are “bad” or “useless” tests. Clearly they aren’t. The available data do clearly show a significant correlation between the predictions made by these tests of risk for more or less aggressive disease and the short-term outcomes of patients after surgery and radiation therapy. However, as we have said before, all these data are based on retrospective studies, which raises the question of their day-to-day, practical, clinical value in predicting patients’ long-term clinical outcomes.

To quote Scott Tomplins, MD, PhD (an assistant professor of pathology and urology at the University of Michigan in Ann Arbor), who was one of the discussants after Dr. Cuzick’s initial presentation,

In prostate cancer, [tests like these] can certainly make some men more confident in their decision to choose active surveillance, but if you were to tell a patient that their risk [of progression on active surveillance] goes from 4 percent to 8 percent, is that enough to change a treatment decision?

The “New” Prostate Cancer InfoLink wants to be clear that we are keen to see tests like these fully developed and supported by better, prospective data. Representatives of Genomic Health were very clear in talking with us at ASCO that they were committed to the development of such data (but that is going to take time). In the meanwhile, we can see why men who seek greater clarity about whether they should or should not consider active surveillance might want to have tests like this done to assist their decision processes. … However, we say that with the warning that the prospective data still to come may demonstrate some very different outcomes when compared to those currently projectable based on the retrospective data. On top of which, the willingness of payers to cover the costs of these tests over time is still a major unknown … and these tests are not cheap.

8 Responses

  1. The link to the Medscape article doesn’t go anywhere?

  2. Sorry about that … It’s fixed now.

  3. Putting this together with the post on Sweden’s experience with AS, it seems to me that these tests are quite promising. According to the post on Sweden from a couple of days ago, they have quite a few men with intermediate (as classified without the CCP score) levels of risk opting for AS. (I liked your US vs. Swedish dueling perspectives on why each country does or does not make use of AS).

    Here in the good old USA, it’s all about having enough confidence to not treat a cancer. That kind of goes against American thinking in general … we see a problem and we think we can, and indeed must, fix it. We have, after all, been in a long “War Against Cancer”. (On a side note, consider how over the top we’ve gone in the “War on Terrorism”. The other day they arrested a kid that works at DisneyLand for playing around with dry ice in a plastic bottle and are holding him on $1 million bail. Absurd.)

    In any event, if the best these tests could do was adjust your risk estimate from 4% to 8%, then they would be of limited use. But earlier in the article the statement is made “For patients with intermediate risk (a CAPRA scores of 3 to 5) and a 10-year mortality risk of 12%, the addition of CCP scoring led to “a huge separation,” boosting some patients’ risk to 25% and lowering others to 5%.” That is a big deal. If we can be very confident that the cancer is not going to advance much over the next year or two, then it becomes so much easier to wait. So, the value is not that the estimate changes from 4% to 8%, but that you know the estimate shouldn’t really be 25%.

  4. I think the research should be more focused towards finding a non-invasive cure (or a proven way to prevent metastases without affecting quality of life) for localised, non-agressive prostate cancer (as well as finding better ways to keep stage IV prostate cancer in check , but that is already thankfully being done) rather than on all these next to useless tests to determine aggressiveness of prostate cancer.

    I wonder why there isn’t any research being done on vaccines for typical low-risk prostate cancer. Seems intuitive that if a vaccine might slow aggressive, metastatic prostate cancer, then a (perhaps slightly different) vaccine might well turn out to be the perfect weapon against low-risk prostate cancer, a nearly perfect compromise between aggressive, often unnecessary treatment and the stressful (to some patients) watchful waiting.

  5. Dear Doug:

    For the patients whose risk for clinically significant disease changes from 5% to 25% (or better still, from 25% to 75%), I don’t think there is any question that having such a test would be helpful … but such patients are probably going to be in a very small minority, which means that we are now adding another $3,000 or $4,000 test for an awful lot of patients, and most of them won’t really get definitive information. And the data are still retrospective, not prospective!

  6. Dear Pawel:

    I think you might be surprised how much effort (and money) has been invested over the years in seeking immunotherapies (“vaccines”) against early-stage and low-risk forms of cancer. The problem seems to be that unless there is an infection-related cause for the cancer (as, for example, with HPV in cervical cancer, against which we now have two vaccines of the type you describe), we have to date been unable to find a way to stimulate the immune system effectively against the actual cancer itself.

  7. Some people may be interested in an article by Peter Ubel that appears on line in Forbes today and suggests an entirely different way to consider the efficient use of diagnostic/prognostic products like Prolaris and Oncotype DX. The article’s title, “Is there a smart way to use the new Oncotype prostate cancer test?” might be considered a tad misleading by some readers.

  8. Thanks for the Forbes link. I’m wondering if that “action imperative” may be more relevant to US citizens than to Swedes (or Europeans in general) as I suggest above.

    In response to the small number of folks who are going to have their risk adjusted from 5% to 25% … it doesn’t matter that it’s going to be a very small number. The point is, it gives all the folks whose risk is just 5% considerable additional certainty that their risk is truly just 5%. So those folks are paying $4K to validate that it’s safe to pursue AS. The other folks are paying $4K to discover that they need aggressive treatment sooner rather than later. (If, as the Forbes article suggests, they are going to opt for aggressive treatment anyway, then the test is kind of pointless for them. Maybe the author has a good idea).

    And, finally, there is a small company called Nymox that is testing an injectable treatment for benign prostatic hyperplasia to see if it will also slow the growth of prostate tumors. I have questions about the company (such as why their drug has been tested so long without coming to market). But, it is an example of a company trying to treat non-aggressive cancers.

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