Risk for and detection of clinically significant prostate cancer in previously unbiopsied patients


The “best” way to identify clinically significant, localized prostate cancer continues to evolve. But there is still no consensus about what that “best” way might be to do this, let alone any consensus about the detection of “clinically insignificant”, localized prostate cancer.

Back in 2018, we commented on the results of the PRECISION trial, a randomized, multi-center, Phase III trial designed to compare whether patients who had an MRI scan prior to biopsy and then only an MRI-targeted biopsy, were more accurately diagnosed with prostate cancer than men who had just a systematic, 10- or 12-core, TRUS-guided biopsy. The results of that trial were clear. The men who had an MRI and an MRI-guided biopsy were more accurately diagnosed. However, we expressed concern about the results of the PRECISION trial because, at the time, we felt that the “best” way to identify clinically significant, localized prostate cancer was by giving patients an MRI followed by an MRI/TRUS fusion-guided biopsy.

Data from another randomized, Phase III trial — the PRECISE trial (reported by Klotz et al.) — have now just been published in JAMA Oncology. The PRECISE trial was also designed to compare the outcomes of patients who had previously been undiagnosed and unbiopsied when they were randomized to either

  • An MRI-guided biopsy if an MRI showed a PI-RADS score of ≥ 3 or
  • A straightforward, systematic, 12-core biopsy (with no prior MRI)

All eligible patients had to have a risk level for diagnosis of prostate cancer that was ≥ 25 percent based on use of the Prostate Cancer Prevention Trial (PCPT) Risk Calculator.

The bottom line, once again, was that the combination of an MRI and an MRI-targeted biopsy did better than a systematic, 12-core biopsy with no prior MRI.

A total of 453 patients were enrolled in the PRECISE trial. Of these 453 patients:

  • 227 were randomized to the MRI + MRI-guided biopsy arm, of whom 221 actually went on the have the MRI
  • 226 were randomized to the systematic, TRUS-guided biopsy arm, of whom 202 went on the have the biopsy
  • A lesion with a PI-RADS score of ≥ 3 was detected in 138/221 men (62.4 percent) of men who were given an MRI and therefore had no biopsy
  • 83/221 men (37.6 percent) had a negative MRI result (i.e., a PI-RADS score of 2 or less)
  • Of the 138 men who had a positive MRI result, 136 (98.6 percent) went on to have an MRI-guided biopsy.
    • 34/136 had a negative biopsy finding.
    • 102/136 had a positive biopsy finding.
      • 23 were found to have Grade Group 1 prostate cancer.
      • 79 were found to have Grade Group 2 prostate cancer.
      • 30 were found to have Grade Group 3, 4. or 5 prostate cancer.
  • Of the 202 men who were given a systematic, 12-core biopsy
    • 86/202 had a negative biopsy finding.
    • 116/202 had a positive biopsy finding.
      • 49 were found to have Grade Group 1 prostate cancer.
      • 67 were found to have Grade Group 2 prostate cancer.
      • 25 were found to have  Grade Group 3, 4, or 5 prostate cancer.

Klotz et al. conclude, accurately, that the combination of an MRI scan and an MRI-guided biopsy in men at evident risk for prostate cancer

results in similar detection rates of clinically significant prostate cancer in the [intention to treat] population compared with systematic biopsy in all men while avoiding biopsy in more than one-third of men and reducing the diagnosis of clinically insignificant prostate cancer.

They also conclude that

This strategy offers substantial advantages over an initial systematic biopsy.

and this is also true. However, … there are problems …

  • We already know that MRI data and PI-RADS scores cannot be relied on (with a high degree of accuracy) to be predictive of risk for prostate cancer.
  • We have no idea how many of the 83 patients who had a negative MRI (i.e., with a PI-RADS 1 or 2)  might actually have had  prostate cancer and especially any with a Grade Group of 3 or higher.
  • We have no idea how many of the patients (in either arm of the trial) might have been found to have prostate cancer if they had had an MRI/TRUS fusion-guided biopsy.
  • We have no idea how many of the patients might have been shown to be a risk from prostate cancer through the use of other tests — such as a genomic test or a test like the (potentially) soon-to-be approved miR Scientific Sentinel™ urine-based test (which Klotz and his colleagues have also been significantly involved in developing).

We would note that this is not, in any way, a criticism of the PRECISE study. On the other hand, it does seem to us that we still have a long way to go before we can define, with a high degree of accuracy, the “best” ways to

  • Identify those patients who really don’t need a biopsy at all because their probability of being found to have clinically significant prostate cancer is truly negligible (say < 2 percent)
  • Identify those patients who can decide at a point in time that their risk for clinically significant prostate cancer is < 25 percent and so they may be able to defer an immediate biopsy but should (perhaps) be monitored for any increase in that risk
  • Determine what the “best” biopsy technique is to ensure that a man who arguably needs and wishes to have a biopsy can be accurately diagnosed using such a biopsy and whether this can be done with only an MRI-guided biopsy or requires an MRI/TRUS fusion-guided biopsy

An editorial by Rouvière in JAMA Oncology addresses some — but not all — of these issues. Another commentary, on the MedPage Today web site, also reports on the results of the PRECISE trial and some of these related issues.

Editorial note: We thank one of our regular readers for providing us with the full text of the original paper by Klotz et al. as well as the full text of the editorial by Rouvière.

 

 

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