Let’s compare the media hype to the actual data (about MR-guided biopsy)

According to an article online in The Australian today, “Men won’t need to have numerous painful needles in their rectum to find out if they have prostate cancer anymore”. However, the article is short on facts and long on emotive language.

Supposedly, two researchers at the Wesley Research Institute in Brisbane, Queensland have worked out a way to use MRI imaging to identify, target, and “micro-biopsy” specific areas in the prostate. However, the article offers no information about the accuracy of this technique, let alone whether this diagnostic technique can provide the level of diagnostic information necessary to determine whether an individual patient actually needs treatment or not.

The “New” Prostate Cancer InfoLink is always interested in advances is the diagnosis and management of prostate cancer — but we do like actual data that allow us to make realistic evaluation of the potential of such advances in real clinical practice.

A media release from the Wesley Research Institute provides some more information, related to an article in European Urology. However, it does not appear to us that the available data in that media release can be used to justify all the hype either.

If you give a man with an elevated PSA a multiparametric MRI (mpMRI), and it doesn’t show any area of the prostate that needs to be biopsied, that doesn’t actually mean that the man doesn’t have an identifiable tumor. It just means you couldn’t see it on the MRI! So then, when you don’t do a biopsy, naturally you can’t fail to find it! And when you do do a “micro-biopsy” into an MRI-visible area of tissue that looks like cancer, you have a very high probability of a positive result.

So this takes us to the actual abstract of the paper on which all this is based (a paper by Pokorny et al., published on line yesterday).

Pokorny and his colleagues set out to compare the diagnostic efficacy of the MRI-based pathway with a standard TRUS-guided biopsy, based on data from a series of 223 consecutive biopsy-naive men referred to a urologist with an elevated PSA level. The study was a prospective, single-institution, investigator-blinded, diagnostic study carried out between July 2012 and January 2013. The “single institution” involved was Brisbane’s Wesley Hospital.

All 223 participants were given an mpMRI and a TRUS-guided biopsy; the men with equivocal or suspicious lesions on mpMRI also underwent the MR-guided “micro-biopsy”.

Here are the findings:

  • 126 cases of prostate cancer were detected by TRUS-guided biopsy.
    • 47 of these cases (37.3 percent) were classified as low risk.
    • 79 of these cases (62.7 percent were classified as intermediate/high risk.
  • 142 men were identified as having an equivocal or suspicious mpMRI.
  • Among those 142 men, MR-guided “microbiopsy” identified 99 cases of prostate cancer.
    • 6 of these cases (6.1 percent) were classified as low risk.
    • 93 of these cases (93.9 percent) were classified as intermediate/high risk.
  • The MR-guided “microbiopsy” path
    • Reduced the number of biopsies “needed” by 51.0 percent
    • Decreased the diagnosis of low-risk prostate cancer by 89.4 percent
    • Increased the detection of intermediate/high-risk prostate cancer by 17.7 percent.
  • The negative predictive values of the two type of biopsy for intermediate/high-risk disease were
    • 71.9 percent for TRUS-guided biopsy
    • 96.9 percent for MR-guided “microbiopsy”.

The authors note that the main limitation of this study is the lack of long follow-up, while concluding that the combination of mpMRI followed by MR-guided biopsies of selected patients

reduces the detection of low-risk [prostate cancer] and reduces the number of men requiring biopsy while improving the overall rate of detection of intermediate/high-risk [prostate cancer].

Now The “New” Prostate Cancer InfoLink does not dispute the value of this study, but we also do not believe it justifies the hype in either the media release or the article in The Australian.

We have no significant follow-up data on these patients whatsoever. As the authors themselves observe, long-term follow-up on all the patients with negative results of any type will be essential before we can tell whether there has been significant risk for under-diagnosis and/or under-grading in the patients diagnosed with low-risk disease by TRUS-guided biopsy.

What is also not clear from this study is why the number of patients identified as having an “equivocal or suspicious mpMRI” included such a small number of patients with low-risk prostate cancer. (This may be explained by additional data in the full text of the paper, which we have not seen.)

Are there potential benefits to be gained from mpMRI evaluation and MRI-guided “microbiopsies”? Sure there are. However, at this point in time, The “New” Prostate Cancer InfoLink is very clear that an mpMRI and a follow-up MR-guided “microbiopsy”can not yet be considered to be an appropriate standard of care for the identification of prostate cancer that needs treatment (as opposed to indolent prostate cancer that can be ignored). And what, for example, does one do with the men who have an elevated PSA but no signal of risk on an mpMRI? Is one just going to tell them they can go home because they don’t have prostate cancer, or do they also need follow-up re-evaluation on a regular basis (“active monitoring”)?

It should also be noted that there is a great deal of skill and experience needed to be able to appropriately “read” mpMRIs and appropriately identify patients with “equivocal or suspicious” indications of prostate cancer. The vast majority of radiologists do not have that level of skill as yet.

17 Responses

  1. If verified, 96.9% negative predictive value seems far better than anything else out there.

  2. Yes, but as noted above, this is a negative predictive value based on only biopsying “equivocal or suspicious” signals on mpMRI, and it is unclear whether those signals are themselves accurate.

  3. I think the most important point is the last one you made. It takes a great deal of experience to read these, and the inter-observer differences are quite high.

    My knowledge is limited to one program (at UCLA) where they use mpMRI as a tool, but do not depend on it totally. They still take cores from random areas to pick up microfoci and other tumors that may not show up on an MRI. Unlike TRUS, it also finds anterior tumors, which is a benefit of particular interest to African-American men, and those for whom suspicion of PC persists despite negative TRUS-guided biopsies.

    In the hands of an expert radiologist, it is an excellent tool from distinguishing low-risk men — who can be safely monitored on AS, which would include follow-up mpMRI-guided biopsies — from higher risk men who require treatment. My question is how cost-effective it is — should it be used for initial biopsies, repeat biopsies after negative biopsies, and/or in conjunction with active surveillance programs?

  4. Allen:

    Unfortunately, here in the USA all MRI scanning is often ridiculously expensive (compared to the costs everywhere else in the world). Furthermore, costs vary dramatically from place to place. As a consequence, here in the USA (surprise) it is extremely difficult to ascertain what is cost effective and what isn’t. However, at present, here in America, I suspect it is highly unlikely that using initial mpMRI scans for all patients is going to be even close to cost-effective. You will note that in Australia the cost of the mpMRI was only about A$500, which is peanuts by comparison with what one might have to pay here.

  5. The other possible cost-effective uses for mpMRI include ways it can be used to prevent or forestall unnecessary biopsies, which may be more costly than the MRI, depending on where its done. (1) Initial mpMRI screening to possibly avoid an initial biopsy, raises big safety issues, which are best examined in a RCT. (2) negative mpMRIs after negative biopsies (and rising PSA) may prevent unnecessary repeat biopsies in a cost-effective way. (3) For men on AS with a couple of biopsies that show indolent tumors, perhaps an mpMRI may be used without the third biopsy if no growth is apparent.

  6. Dear Allen:

    There is no doubt in my mind that we are gradually going to see a far greater role for mpMRIs in all three of the areas that you outline. I would also note that CMS has the power to “bundle” reimbursement for certain types of medical care. For example, they bundle annual payments for dialysis for patients with end-stage renal disease. Why could they not bundle annual payments for active surveillance, which might well lead to significant downward pressure on the reimbursement for mpMRIs.

    The other factor that is going to be important in all of this is the training of radiologists to read prostate-specific mpMRIs in a standardized manner, so that everyone is “comparing apples to apples”. At present there is no standardization, and relatively few radiologists are highly skilled and experienced in reading these mpMRIs.

  7. •The negative predictive value was 96.9 percent for MR-guided “microbiopsy

    How did they determine this? Did they follow up with a full specimen dissection, after a RP?

  8. Doug:

    This is a statistical result based on the number of men who had a suspicious MRI and the number of positive biopsies among that subset of men. They report no information about the subsequent treatment or pathology of any of these men, which is one of the reasons I so dislike the hype associated with this paper.

  9. My close family member had two negative TRUS biopsies with a continually rising PSA, negative exams, and no clinical symptoms. He also had two negative standard MRIs and three negative color doppler exams. All this was done over a 3-year time span. March 2013 we decided to go out of insurance network and seek a 3-T MRI-guided biopsy by a specialist in NYC. Gleason 9 with extensive lymph node involvement was found, anterior tumor. He is responding well to treatment, we are only sorry we did not do the MRI-guided biopsy sooner. (Only through private research did we find out about it.) To us this biopsy was superior, oh and painless according to the patient. With a well-educated radiologist and appropriate equipment this may be a better predictive path to follow for many men.

  10. An awful lot of this study depends on data not yet included. What was the threshold for referral? Was that the normal standard? Were those doing referrals aware of the study? Was staging consistent and reviewed?

  11. Susan:

    Who did the biopsy? What treatment did you choose?

  12. Dr Sperling is a radiologist who trained outside the US. We waited a long time but he spent 2 hours with us.

    Casodex and Lupron for 7 months; radiation the fourth month (x 30 sessions); Now just on Lupron q3 months. Also use alternative medicine and eat mostly organic; not vegetarian.

    Diagnosis is stage D1, Gleason 9. Prognosis was poor by surgical urologists (saw 3). Being treated by medical oncologist now. Response to treatment is remarkable, we have been told. PSA went from 928 to below 0.05; all bloodwork excellent, feels great. Please ask me any other questions in the future. I study prostate cancer several hours a day, worldwide treatments. We knew little as of a year ago.

    Good luck to you Doug,


  13. Dear Susan:

    I am glad to hear that your spouse/partner has been doing well on radiation and long-term ADT. This is now a pretty standard way to treat someone with D1 disease (commonly known today as TxNxM0 disease). And this sort of drop in PSA level is actually not as unusual as many people might think. The critical question, of course, is going to be how long the PSA remains down at about 0.05 ng/ml.

  14. Thank you for responding.

    We are aware that this treatment is typical for D1 prostate cancer, but in my family member’s case were told not to expect his PSA to fall below 1 with the amount of lymph gland involvement. We were also told that radiation was not typical with the extreme size and number of lymph glands (very unusual, we were told; few doctors had ever seen this). We had to argue our point for it. It was declined twice.

    We were seen by several top specialists in New York City. His actual stage is T4N5+. I am so glad you say it is not unusual; that is what our research lead us to believe. We had been reading a great deal from Meyers and Strum which lead us to push for the radiation. Supplements and treatments used in Japan gave us hope.

    Intermittent Lupron is now being discussed. The timing of this seems to be vague in most literature: 18 months on Lupron (based on new study in Europe)? 12 months in complete remission? Or the usual 2 years? Prior to our last visit we were told Lupron for the rest of his life. We are comfortable with 18 months.

    Thank you.


  15. Dear Susan:

    The type of diagnosis you describe is much less common today than it was 20 years ago, so a lot of younger clinicians have not seen this type of initial diagnosis.

    The issue of whether intermittent therapy is going to be appropriate in your family member’s case is not well defined. Certainly, if his PSA had not fallen down to the level it has, I don’t personally think that IADT would have been appropriate; and even though the PSA has fallen down into the effectively “undetectable” range (< 0.1 ng/ml) there are still good arguments to suggest that he should not consider this option until it is clear that he has had the best possible response to the combination of radiation + adjuvant ADT.

    I am not a physician, and so my opinions are based solely on 25 years of studying the prostate cancer literature. However, if the primary goal for your relative is survival, I would argue that his best bet was to stay on the ADT for a full 3 years and then, if his PSA is still stable and below 0.1 ng/ml, one could consider IADT at that time. I say this because your relative was at the extreme upper end of men eligible for treatment with the combination of radiation + adjuvant ADT (given his Gleason 9 disease and the PSA of 900+ ng/ml).

    On the other hand, if quality of life is the priority (and extent of life is secondary), then you could certainly consider trying the IADT at 18 months if the PSA is still stable.

    In the end, this is a matter of choice for the patient in discussion with his doctors. What the rest of us may think may be informative, but it is not clinically definitive. No one has good enough data to make high probability bets in a case like this.

    If I was your relative, and I wanted to do IADT, I would also tell my doctors that I wanted to start dutasteride treatment (Avodart) along with the Lupron, and that I would then want to stay on the dutasteride when I came off the Lupron (so that the dutasteride continued to block the conversion of testosterone to dihydrotestosterone, thereby [potentially] extending the length of the off-Lupron cycle).

    One last comment. If you join our social network, it is a lot easier to have this type of extensive discussion than it is on the main web site, and it is a lot easier for the other 4,000+ members of that network to join in the conversation.

  16. Susan,

    Glad to hear your husband is doing well.

    Did Dr. Sperling laser ablate the tumor, as well. From what I know, this is his usual treatment.


  17. Hello Doug.

    No, he did not laser the tumor as it was not confined to the prostate.


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