Is free, circulating DNA a useful marker for prostate cancer?

Elevated levels of free, circulating DNA (fcDNA) have previously been been found in the serum of prostate cancer patients compared with the levels in the serum of patients with benign prostate conditions.

A new report from Gordian et al. has examined the potential role of fcDNA as a biomarker for prostate cancer in a cohort of patients undergoing normal prostate cancer testing. This study was based on data from 252 men, all of whom had a PSA level  > 4 ng/ml and/or and abnormal digital rectal exam. The levels of fcDNA in the men’s serum before they received a prostate biopsy was based on PCR amplification of a gene coding for an enzyme known as glutathione S-transferase — the so-called pi gene.

The results of this study showed that

  • Patients with a PSA level  ≤ 10 ng/ml and with an fcDNA level > 180 ng/ml were at significantly  increased risk for prostate cancer compared with those with an fcDNA level ≤ 180 ng/ml (odds ratio = 4.27).
  • A multivariate model (including age, race, PSA, fcDNA, and interaction between fcDNA and PSA) yielded a negative predictive value of 93.1 percent compared with negative predictive value of 73.3 percent in a model that did not include fcDNA data.

The authors conclude that that fcDNA data may be able to improve the specificity of prostate cancer testing, which would potentially lead to a reduction in the number of unnecessary prostate biopsies.

The “New” Prostate Cancer InfoLink (as is often the case) believes we need additional data from an independent group of investigators to substantiate these initial findings. However, a specificity is 93.1 percent is a distinctly high degree of accuracy if it can be replicated. We should hasten to add that there are no data (yet) to suggest that this test is able to distinguish between clinically significant and indolent forms of prostate cancer.

8 Responses

  1. But researchers are trying to find out how to differentiate between slow growing and aggressive prostate cancer. Next step.

  2. If it can’t distinguish between indolent and aggressive forms of prostate cancer, it’s money down a rat hole. What can we do to stop spending dollars on testing that increases the risk of inappropriate, life-altering treatment for 47 out of 48 men?

  3. A test that meant that 75-80% of men who currently need a biopsy that turns out to be negative could avoid that biopsy would not be “money down a rat hole,” Tracy.

  4. Hmmmmmm … more deja vu!

  5. By definition a test that could distinguish between aggressive and indolent cancers would classify who needs further diagnosis and treatment and who needs observation.

    A whole lot of energy (and lots of research dollars that could be spent on other things — like distinguishing between prostate cancer that is truly a risk to men’s lives and prostate cancer that’s not) appears to be spent trying to avoid prostate biopsies. While there are certainly real risks to biopsies, infection, bleeding, etc., the risks are relatively small (certainly not on the scale of risk of quality of life outcomes from prostate cancer treatment) and very manageable. And believe me, I get it that prostate biopsies are a relatively inadequate as a diagnostic tool (too many “misses”).

    However, it seems in some ways that the desire to avoid biopsy is more culturally driven than medically desirable. While no one wants to be unnecessarily penetrated (until they do), it is more than a little ironic that we’re spending precious research dollars to avoid a 5-minute, comparatively low-risk diagnostic procedure at the cost of finding diagnostic and treatment procedures that would protect men from being rendered impotent for decades at odds as high as a flip of of a coin.

    Imagine an anonymous, representative poll of men where they’re asked: Would you rather the medical research industry finds a way for you to avoid having your rectum penetrated for a 5 minute test or would you rather we find a way to cure prostate cancer that doesn’t destroy your ability to ever again feel an orgasm? My guess is they would find the former a fairly inconsequential invasion compared to the benefit of the latter’s long-term good.

  6. Tracy:

    I don’t think that any of the money that commercial companies put into research is designed or intended to develop tests that will “avoid the need for a biopsy.” I think that tends to be a possible outcome of research that starts out trying to find a much better diagnostic test for prostate cancer than a PSA test. The problem is that finding a test that really can distinguish between clinically significant and indolent prostate cancer has been extremely difficult (although we may be getting closer).

    Finding curative treatments for prostate cancer than have truly minimal side effects has been even harder, but I don’t disagree with your premise.

  7. Just a reminder that generations of individuals pay a huge price for embracing an incrementalist approach to treatment. Sometimes advocacy is about making it clear that “not good enough” is truly not good enough.

  8. Thanks for posting this news.

    While it needs confirmation, I’m impressed with the specificity and how it complements PSA.

    By way of perspective, chapter 8 of Dr. Scholz new book (with Ralph Blum), Invasion of the Prostate Snatchers — No More Unnecessary Biopsies, Radical Treatment or Loss of Sexual Potency, gives his approach to trying to limit unncecessary biopsies. He mentions the importance of estimating the size of the prostate with ultrasound, calculating PSA density and PSA velocity, and use of the PCA-3 test, but with a relatively small role for the free PSA assay. He touches on using finasteride or Avodart to increase the usefulness of PSA testing.

    However, it’s pretty clear that an additional indicator would be welcome.

    There is no reason why such an indicator and other research targets, such as homing in on potential lethal prostate cancer, could not be pursued.

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