Who really needs to be given a prostate biopsy?

A newly published article in Reviews in Urology argues that, on economic grounds alone, the majority of patients thought to be at risk for prostate cancer should have a 4KScore test prior to them being given a biopsy since this test can rule out the need for biopsies with a high degree of accuracy.

Now one can quibble with this suggestion for all sorts of possible reasons, including the idea that there are other tests that might be just as good at ruling out the need for a biopsy. The full text of this paper by Voight et al. is available on line for those who are interested.

What one can not quibble with is the fact that prostate biopsies come with a significant risk for complications, some of which are serious and require hospitalization (which is very expensive indeed, especially if the patient has septicemia as a truly life-threatening complication of their biopsy).

What this paper does do, therefore, is further elevate the question of how best to determine who really does and who really doesn’t actually need to have an early biopsy after an initial PSA test suggests possible risk for prostate cancer in a man with no other apparent signs or symptoms of such risk.

The currently available tests that could relatively easily be given to such patients include:

  • A %free PSA test
  • A Prostate Health Index or phi test
  • A 4KScore test
  • A multiparametric prostate MRI scan

Other tests that could be considered (but have yet to be well validated in this situation) might arguably include

  • The new isoPSA test (still in development)
  • The new ExoDx™ Prostate(IntelliScore) test (available but yet to be validated prospectively)
  • The older PCA3 tests (which appear to be less than completely reliable)

With the exception of the MRI scan, all of these tests can be run on either a blood sample or a urine sample.

It would seem to your sitemaster that the time has come for someone to look into a carefully constructed prospective study that could be carried out in a large set of men (i.e., 1,000 or more) who were initially diagnosed with a PSA level of (say) > 3 ng/ml and < 20 ng/ml, a negative rectal exam, and no other evident signs or symptoms of risk for prostate cancer who then received all of these tests (with the possible exception of the PCA3 test) and who went on to have an MRI/TRUS fusion biopsy that combined a standard 12-core biopsy with targeted biopsies of evident areas of risk shown on MRI.

Data from such a trial should be able to allow us to determine:

  • Whether there was one single such test that allowed us to rule out the need for prostate biopsies in such men with a very high degree of certainty (probably unlikely)
  • Whether there was a combination of two such tests that could have the same effect (possibly much more likely).
  • Whether there were certain patients with exceptional indicators of need for biopsy among such patients that could not be currently identified by the available tests.
  • Whether using such a testing process would be cost-effective by comparison with the current general strategy of moving straight to a standardized 12-core biopsy.

While we continue to give biopsies as a first element of the diagnostic work-up for every patient who is at possible risk for prostate cancer, we also continue to put hundreds of thousands of men at risk, every year, for  the complications of those biopsies. This is not good medicine … and it is probably also not particularly cost effective.

The one fly in the ointment in the current conduct of such a trial is that high-quality, multiparametric MRI scanning and high-quality interpretation of the results of such imaging are not available in a standardized fashion to men across the USA as yet.

If others have better ideas, we’re listening.


7 Responses

  1. Good idea, but the trial should use in-gantry biopsy, not fusion.

  2. Dear Doug:

    The tiny number of centers where in-gantry MRI biopsies is a possibility at the present time make this a practical impossibility.

  3. This is exactly what was done for PHI to get its FDA approval (see this link). It predicts significant prostate cancer reasonably well (see this link and see this link). Its diagnostic accuracy is probably about the same as the other multi-kallikrein-based markers like 4Kscore and isoPSA (see this link and see this link). I am hopeful that a new biomarker called %α2,3-sialic acid PSA in addition to PHI will be the magic test we’re seeking. In an early trial, the two combined had 100% sensitivity and 97% specificity and was not affected by BPH ((see this link). It’s not ready for prime time, of course.

    Because PHI is FDA approved, covered by insurance and Medicare, and relatively inexpensive (I’ve heard quotes of about $125), I recommend it to patients over the others. One of the more exciting potential uses is for monitoring patients on active surveillance.

  4. T2:ERG plus PCA3 (MiPS) may be helpful.

  5. @Allen Edel: “One of the more exciting potential uses is for monitoring patients on active surveillance.” Please elaborate, since you have described it as a binary test. Does it also convey degree in your view; i.e., would it supplement the MRI and (hardly) PSA I rely on?

  6. Actually, withdraw that. The test is for significant prostate cancer, so by its nature binary.

  7. It has been explored for use with active surveillance, but will require long-term validation. Here are a few studies you may find of interest:

    PHI and PCA3 improve the prognostic performance of PRIAS and Epstein criteria in predicting insignificant prostate cancer in men eligible for active surveillance.
    Active surveillance for prostate cancer: a systematic review of clinico-pathologic variables and biomarkers for risk stratification
    Elevated Prostate Health Index (phi) and biopsy reclassification during active surveillance of prostate cancer

    This one shows how lower PHI predicts staying on active surveillance:

    Evaluation of the prostate health index (phi) as a novel biomarker in active surveillance of prostate cancer

    Yes, it would supplement mpMRI in helping to determine whether a repeat biopsy is warranted on active surveillance:

    The Prostate Health Index adds predictive value to multi-parametric MRI in detecting significant prostate cancers in a repeat biopsy population
    In-parallel comparative evaluation between multiparametric magnetic resonance imaging, prostate cancer antigen 3 and the Prostate Health Index in predicting pathologically confirmed significant prostate cancer in men eligible for active surveillance.

    Because phi includes PSA (and %free PSA) and is relatively inexpensive and covered by Medicare/insurance, a patient on active surveillance really has little to lose by monitoring with phi instead of PSA alone.

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