MRI-guided biopsy in the diagnosis of prostate cancer (again)

The results of the so-called PRECISION trial were just published in the New England Journal of Medicine this morning.

The PRECISION trial was a randomized, multi-center trial conducted in previously undiagnosed men thought to be at risk for prostate cancer and it was designed to compare the outcomes of a standard, 10- to 12-core, transrectal ultrasound-guided biopsy in men who did not get an MRI scan prior to biopsy to those of an MRI-targeted biopsy alone after an MRI scan. (For more details of the trial design, please click here.) The trial enrolled a total of 500 men in 2016 and 2017.

It is important to understand that, among the men in the MRI-scanned arm of the trial, patients who showed no sign of prostate cancer on their MRI scan did not receive a biopsy at all, of any kind. Also, the men who received an MRI scan only had biopsy samples taken from the regions of the prostate that showed risk for prostate cancer, so, for example, some men in this arm of the trial might have had just one biopsy core taken.

What Kasivisvanathan et al. report finding is as follows:

  • Among the 252/500 men randomized to the MRI-targeted biopsy group,
    • 71/252 (28 percent) were negative for risk of prostate cancer on MRI results and were given no biopsy.
    • 95/252 (38 percent) had a positive MRI-targeted biopsy result — or 95/181 of the men who were given a biopsy (52 percent)
    • 86/252 (34 percent) had a negative MRI-targeted biopsy result — or 86/181 of the men who were given a biopsy (48 percent)
  • Among the 248/500 men randomized to a standard TRUS-guided biopsy
    • 64/248 (26 percent) had a positive TRUS-guided biopsy result.
    • 184/248 (74 percent) had a negative TRUS-guided biopsy result.

They go on to state the following:

  • MRI, with or without targeted biopsy, was noninferior to standard biopsy, and that
  • Fewer men in the MRI-targeted biopsy group than in the standard biopsy group received a diagnosis of clinically insignificant prostate cancer.

They conclude that

The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography–guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously.

The New England Journal of Medicine also includes an editorial commentary on this article by Barry and Rosenkrantz, but only the first 100 words of the editorial are available to those of us who are not subscribers to the NEJM.

In all honesty your sitemaster is more than a little concerned by this article, and he hopes that, in their editorial, Barry and Rosenkrantz have also expressed some of these concerns.

First, we know from other studies that standard TRUS-guided biopsies can find clinically significant prostate cancer in men when it is not found by MRI-targeted biopsies. Does this happen frequently? No. Does it happen often enough to be worrisome? Yes, it does.

Second, we know that even 3 T MRI scans read by real experts in uroradiology are going to “miss” very small foci of cancer. So one has to ask how many cases of clinically significant prostate cancer might have been “missed” in this study because the patients with a negative MRI scan never got a biopsy at all.

The problem here is that the failure to diagnose even one man with a high-risk (Gleason 8 to 10) form of prostate cancer could lead to a death that might have been prevented.

In your sitemaster’s mind, it is fine if an individual patient, having had the risks appropriately explained to him, chooses to have only an MRI-guided biopsy. That has then become the individual patient’s decision. Your sitemaster has yet to be convinced that MRI scanning is capable of identifying all high-risk prostate cancer (let alone all “clinically significant” prostate cancer).

What the results of the PRECISION trial have shown us is that in men who have a positive MRI scan and who have biopsy samples taken only from those areas of the prostate that show positive for risk of prostate cancer

  • The results of the MRI scan are actually demonstrably accurate in identifying prostate cancer only 38 percent of the time.
  • A “blind” 10- to 12-core TRUS-guided biopsy detects prostate cancer only 26 percent of the time in an analogous group of men.

The fact that an MRI-targeted biopsy is better at identifying possible risk for prostate cancer than a blind 10- to 12-core TRUS-guided biopsy should hardly come as a surprise to anyone. But these data do not answer the real unanswered question, which is whether any form of MRI-guided biopsy can — as yet — identify clinically significant prostate cancer with (say) 95 percent accuracy or higher. As far as your sitemaster is aware, that is not currently the case (even when in-bore MRI-guided prostate biopsies are carried out).

When a man is at risk with a potentially low-risk form of prostate cancer, it may well, today, be perfectly reasonable to give him an MRI scan (or not) and then have a conversation with him about the need for a prostate biopsy and how that should be done. However, …

At least in the mind of your sitemaster, as of today, any man who is at risk with a potentially intermediate- or high-risk form of prostate cancer should have an MRI scan and an 10- or 12-core TRUS-guided biopsy together with additional, targeted biopsy cores taken from any area of the prostate shown to be at risk on an MRI scan.

After this, it becomes possible for a patient to make appropriate decisions — in concert with his doctors — about the management of his disease and whether he needs treatment or can be (at least initially) managed on active surveillance.

Without wishing to be critical, your sitemaster considers that the PRECISION trial was flawed by its design. If all 500 patients in this trial had been given both an MRI-guided biopsy and a standard 10- to 12-core TRUS-guided biopsy (sequentially on the same day), we could finally have known just how accurate these two methods of biopsy were when compared to each other in a well-defined set of patients. And it would not have been difficult to carry out the trial in such a way.

Additional commentary about this trial and its results can be found on the MedPage Today web site.

3 Responses

  1. I fully agree with your comments, and they are worth repeating, but I had a sense of deja vu in reading this. You covered this just about a month ago.

  2. Dear Mike,

    Yes, yes and yes! How is it possible that medical professionals can come up with such a flawed trial design? Sadly, this was just one more lost opportunity to improve accuracy in prostate cancer diagnosis.

  3. Oh well … Better twice than not at all! :O)

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