A four-kallikrein panel and biopsy outcomes in previously untested men

In 2008, Vickers et al. initially proposed that a panel of four kallikrein markers, together with patient age, could potentially reduce the need for unnecessary biopsies in previously untested men with an elevated PSA level and a theoretical risk for prostate cancer. The four markers are the serum (blood) levels of total PSA, free PSA, “intact” PSA, and kallikrein-related peptidase 2 (hK2).

In a newly published report, Vickers et al. sought to replicate their original findings in an independent, population-based cohort of 2,914 previously unscreened men who underwent biopsy as a result of a PSA level ≥ 3 ng/ml in the European Randomized Study of Screening for Prostate Cancer, Rotterdam. This cohort of patients included 807 men (28 percent) in whom prostate cancers were, in fact, detected on biopsy.

The results of this study showed the following:

  • Addition of free PSA, intact PSA, and hK2 data to a model containing total PSA and age significantly improved the ability to predict the outcome of prostate biopsy compared to total PSA and age alone.
  • The increase in predictive accuracy of the four-kallikrein model was evident with and without the availability of DRE data.

According to the authors, application of the four-kallikrein panel to 1,000 men with elevated PSA levels would reduce the number of recommended biopsies by 513. However, it would also mean that 54/177 low-grade cancers (32 percent) and 12/100 high-grade cancers (12 percent) would not be diagnosed at the time of initial screening.

This study clearly confirms the earlier finding that a panel of four kallikreins can predict the result of biopsy for prostate cancer in men with an elevated PSA. It also confirms that this panel would dramatically reduce biopsy rates. The question that has to be addressed is whether the use of this panel is appropriate clinically if it simultaneously reduces the probability of diagnosis of 12 percent of men with high-risk disease and 32 percent of men with low-risk disease.

Since men with low-risk disease would presumably continue to get regular tests, there is a reasonable expectation that they could still be diagnosed in time to have curative therapy if it proved necessary. The greater concern must surely be for the men who might not be diagnosed early with high-risk disease. These are the men at highest risk for potentially lethal prostate cancer and therefore the ones who would benefit the most (in theory) from early detection of their disease.

It is worth noting that Vickers and his colleagues have very recently reported data suggesting that the same four-kallikrein model can  be used to predict the outcomes of biopsies with considerable accuracy in men who have undergone prior testing for prostate cancer.

2 Responses

  1. Well, what do you think Doc? Supposing you had a patient with a PSA of say 5 ng/ml, and the patient asks: “Should I get this four-kallikrein panel test, or should we go straight to a biopsy?”

  2. First, let’s be clear: I am not a doctor.

    Second, this kallikrein panel test is not (as far as I know) commercially available at the present time, so I’m not sure I would be able to get the test done very easily.

    Third, I would be concerned about how to interpret the results of this test in any patient with a low PSA who had other clear signals of high risk (e.g., family history; a positive DRE).

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