Increasing our ability to predict who really needs to be biopsied


Data from a large study reported in the July issue of the Journal of the National Cancer Institute has confirmed the potential ability of a four-kallikrein marker test to lower the need for biopsies in men at risk for prostate cancer while delaying diagnosis of high-grade cancers in a few men.

This study by Bryant et al. (which is available on line as a full text article) was based on cryopreserved blood samples from > 6,000 men participating in the so-called ProtecT study in the United Kingdom, where the majority of man still do not undergo routine PSA testing for risk of prostate cancer.

The researchers measured the kallikrein levels of cryopreserved blood in 6,129 men with a PSA level of 3.0 ng/ml or higher. Marker levels from 4,765 men of these men were then used in statistical models to predict any-grade and  intermediate + high-grade prostate cancer (i.e., and Gleason score of 3 + 4 = 7 or higher) on systematic 10-core biopsy. The four kallikrein markers measured were total PSA, intact PSA, free PSA, and kallikrein-related peptidase 2.

Bryant and his colleagues report the following basic findings:

  • The four-kallikrein test was superior to a total PSA test together with age in the detection of prostate cancer.
    • The area under the curve (AUC) for total PSA and age was
      • 0.634 for any-grade prostate cancer
      • 0.738 for intermediate + high-grade prostate cancer
    • The AUC for the four-kallikrein panel of markers was
      • 0.719 for any-grade prostate cancer
      • o.820 for intermediate- + high-grade prostate cancer
  • Using a 6 percent risk of intermediate- or high-grade cancer as an illustrative cutoff, for each 1,000 biopsied men with PSA levels of 3.0 ng/ml or higher, the current model would
    • Reduce the need for biopsy in 428 men
    • Detect 119 intermediate- or high-grade cancers
    • Delay diagnosis of 14 out of a total of 133 intermediate- or high-grade cancers.

The authors are very careful to observe that a definitive evaluation of the utility of the four-kallikrein marker test would necessitate the use of fresh blood samples as opposed to the cryopreserved samples used in the current study. They also point out that definitive utility would require  prospective analysis of samples taken from men with elevated PSA levels in whom urologists had already made the clinical judgment to perform a biopsy. Such a cohort of patients would need to include “all-comers”, irrespective of prior screening, PSA cutoff used, or biopsy history.

They state that just such a study is currently under way in the USA — a study in which kallikrein markers are being measured from plasma in a clinical laboratory within 48 hours of the blood draw, and the biopsy involves the type of 12- or 14-core approaches common in US practice today.

We should note that the four-kallikrein marker panel used in the above study and in the ongoing trial is (presumably) the one already available as the 4KScore test from OPKO Laboratories.

For purposes of future clinical applicability, the “New” Prostate Cancer InfoLink would hope to be able to see data from this and future studies broken down according to the five new prostate pathology grades recently described by Epstein et al. (see this report). These new prostate pathology grades are scheduled to replace Gleason grades over the next few years.

The combination of being able to get much better at determining which patients really need to be biopsied, along with the ability to determine which patients really are good candidates for active surveillance post-biopsy, is starting to shift us away relatively rapidly from the over-treatment of low-risk prostate cancer that was commonplace in the 1990s and early 2000s. This will also help to leave many men with low-risk prostate cancer with a far higher quality of life for a much longer time period.

2 Responses

  1. in the United Kingdom, where the majority of man still do not undergo routine PSA testing for risk of prostate cancer

    “Still” meaning they haven’t been sucked into PSA screening.

    Fortunately some men realise the onus is not on them to disprove that PSA screening works. Doctors try to suck them in with the burden of proof logical fallacy.

  2. Dear Michelle:

    With the greatest respect, I was making no point at all about whether regular PSA testing for risk of prostate cancer was a good idea or not. I was simply reporting a fact.

    The question of whether regular PSA testing is a good idea for individual men rather depends on their known risk levels and what the doctor and the patient do with such data.

    I do not think that annual, mass PSA screening on a population-wide basis is a good idea. I do think it is a good idea for selected men known to be at high risk for clinically significant prostate cancer for any one or more of several possible reasons.

    Like many other issues in medicine, this is not a “black” or “white” issue. … The shades of grey are of critical importance.

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