The genetics of prostate cancer risk — as seen by the WSJ

There’s an article in today’s Wall Street Journal that begins, “Scientists may soon be able to answer the agonizing question facing men with prostate cancer.” The agonizing question is whether a specific individual actually needs early and aggressive treatment for his cancer or can simply monitor it for risk of progression.

The article is primarily focused on research that suggests we are beginning to “tease out” which forms of prostate cancer are genetically predisposed to be more aggressive types of the disease (“tigers”) and need early treatment as compared to those types that can simply be monitored over time, and which will generally be found to be relatively indolent (“pussycats”). The article’s content also refers in detail to recent data from the University of Michigan and from Memorial Sloan-Kettering Cancer Center that has already been discussed on this site.

However, we want to be sure that the idea that “Scientists may soon be able to answer the agonizing question …” is placed in an appropriate context.

It seems highly likely to The “New” Prostate Cancer InfoLink that we are close to the development of genetic profiling methods that will allow a urologist to test for specific genes and to “classify” a newly diagnosed prostate cancer patient as being at greater or lesser risk for clinically significant disease over time based on these tests. However, what we will certainly not have any time soon are prospective clinical data validating the accuracy of that classification system. In other words, we will not be able to say, with a high degree of certainty, that (for example) 87 percent of men with D’Amico low-risk prostate cancer and genetic profile xxxx will never have progressive prostate cancer that becomes clinically significant. It will likely take at least another decade after we develop a genetic profiling system before we can validate such a clinical prognostic system.

So, what we are actually moving toward in the interim is more information that will help a man and his doctor make decisions about what to do, but they will still be making those decisions based on retrospective data as compared to prospective data. Are such retrospective data better than nothing? Sure they are. Are they “good enough”? No they aren’t.

One of the things that has been demonstrated over and over again in the biological sciences is that genetics is not the sole determinant for development of specific clinical disorders. The biological and social environment also has profound impact on the development of disease — even among identical twins with identical genotypes. This is because biologic systems (e.g., man) adapt to their environment in both the short term and the long term. Knowing the genetic profile of a particular subtype of prostate cancer will certainly help us to assess risk for an individual patient. However, it will not be the only factor that affects risk for progression of prostate cancer, which is a complex disease which seems to have multiple “trigger points” in the evolution of specific cases from small, localized tumors in the prostate to progressive, extraprostatic disease that may become lethal.

In saying this, we don’t wish in any way to undermine the importance of genetics. One of the things clearly shown by Bova and his colleagues at Johns Hopkins last year was that most (but not all) cases of lethal prostate cancer can be tracked back, over time, to a specific group of prostate cancer cells in the prostate at the time of diagnosis that come with a particular genetic makeup. In other words, the genetic profile of a specific prostate cancer may be critical to its ability to metastasize and become a lethal form of prostate cancer — but it may not be the only factor. The other thing that Bova and his colleagues showed in this research was that the initial DNA mutations among the patients with lethal disease were all different!

3 Responses

  1. Please describe for us how an individual might operationalize this information today. Where would he go? What kind of test would he ask for? Who should see?

  2. As far as I am aware, this information can not be “operationalized” at this time. To date all data is based on materials from archived tissue and related specimens. There are no recognized, clinically applicable tests to date. These data are based on purely scientific research.

  3. Mike,

    You may recall that I contacted the researchers at Michigan to find out if I could be tested for the RAF oncogene (gene fusion). At first they told me there was no clinical application to their research at the current time. A few weeks later they contacted me and asked if I would like to be put on a list to be tested if their application for a clinical trial was approved. I am on the list.

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