MRI-guided focused ultrasound in focal treatment of low-risk, localized prostate cancer

In October last year, the US Food and Drug Administration approved the ExAblate MRI-guided focused ultrasound technology for the treatment of pain associated with cancer metastasis to bones, which is obviously a potential benefit for men with late stage, metastatic prostate cancer. However, The “New” Prostate Cancer InfoLink was conscious, when we first heard of this technology several years ago, that it would have the potential to be used in the treatment of early, localized forms of prostate cancer.

Apparently a Phase II trial of the use of ExAblate technology in the focal treatment of men with low-risk, early stage prostate cancer was, in fact started, in late 2010. This trial is still enrolling patients at five centers around the world (including centers in Canada, Israel, Italy, Singapore, and the United Kingdom). The trial is only designed to enroll 80 patients altogether, so we are surprised that it is still enrolling patients. However, we hadn’t heard of the trial, so we presume most patients had never heard of it either!

The use of MRI-guided focused ultrasound as a means to deliver focal therapy for low-risk, localized prostate cancer is actually extremely interesting. It comes with a high potential for accurate delivery of high-intensity focused ultrasound to a highly specific target area within the prostate, thereby eliminating small tumors while minimizing the risk for side effects and complications of treatment. One way to think about this type of therapy is that it is HIFU with the potential for increased accuracy.

A recent paper by Lindner et al. reports on the early application of this technology to offer focal therapy. The full text of this paper can, in fact, be downloaded (at no cost) as a PDF from the web site of the Canadian Urology Association Journal if you go to the link to the abstract. The paper provides a single case report of the first case treated by the Canadian investigators, and so we learn little about the long-term effectiveness and safety of the technique from this paper. However, the authors do make a couple of interesting statements based on their experience of treating a 51-year-old male who had a palpable nodule on his right lobe (clinical stage T2a), a PSA of just 1.07 ng/ml, and a Gleason score of 3 + 3 = 6. A 16-core mapping biopsy had shown two positive cores in the right lobe (with only 1 percent of each core positive for cancer). The area of the prostate treated using ExAblate technology was limited to the two regions of the prostate where tumor was evident on biopsy.

Lindner et al. state that:

In our first case, we have demonstrated that this procedure can be performed safely with no adverse effects up to 1 month post-procedure. It also demonstrates that we were successful in devascularizing the area that we targeted, with persistent non-perfusion of the site of ablation at the 1-month follow-up [MRI] scan.

They go on to note that:

We believe that added complexity of using MRI-guided [focused ultrasound] over ultrasound-guided [focused ultrasound] is well worth it for the precision and uniformity of tumor vascularization, as well as the ability to avoid the unwanted tissue damage by monitoring temperatures in the treatment field. The short- and long-term oncologic outcome remains to be determined by sequential biopsies. The present patient awaits repeat biopsy, which will be performed at 6 months post-ablation, as per protocol.

We do need to be clear that overuse of technology like this to treat men with low- and very low-risk disease would probably be unwise, but this type of technology is certainly a potential option for the treatment of some men (and particularly younger men) with small amounts of low-risk disease that progress to intermediate risk on active surveillance … and for the treatment of men with focal areas of low-risk disease who are simply unable to deal with living with cancer in their prostate (however indolent).

24 Responses

  1. As a past HIFU patient with no cancer or side effects, it is encouraging to see greater use of focal therapy in dealing with prostate cancer. And although long-term success data for HIFU are still limited, current HIFU prostate proximity mapping and understanding of temperature ranges for ablation under skilled and experienced physicians improved for the last decade. Too bad many uninformed physicians continue to “sell” their radiation and surgery as a solution without edifying themselves, or their patients, on other treatments.

    Soon it won’t matter, though. HIFU will be FDA approved and patients will be offered less invasive procedures.

  2. Interesting that the trial is with a low-risk patient rather than a late stage patient. Methods that would fail to treat a late stage condition may be very effective with a early stage patient. (What has no effect on a house fire may put out a match.)

  3. Dear Mike:

    I am not sure what you are implying when you say it is interesting that this trial is focused on low-risk patients. This form of therapy is highly unlikely to be curative (or appropriate) for men with high-risk, localized disease. The whole point of this therapy is that it may be both effective and safe in men with low- and perhaps intermediate-risk disease whose cancer is confined to a well-defined area of the prostate. The first step is therefore, very naturally, to see if it is indeed safe and effective in such men with small amounts of low-risk disease before seeing if it can also be used on men with larger amounts of low-risk disease or any amount of intermediate-risk disease.

    The approved use of this therapy (as a palliative form of care in men with bone pain associated with metastatic disease) has already been extensively tested. The technology is also approved for use in the ablation of uterine fibroids in women (a painful and problematic, but not malignant, condition).

  4. Really not implying anything, more pondering the dilemma of patient safety versus medical advancement. Trials with the sickest patients must fail to find benefit for procedures which would help the less advanced patients.

    Here though, in a new use of existing method, a pool of one is rather conservative. If the one is not successful, does that imply the method is without value? Hope not.

  5. Mike:

    Early case data like this are not usually about the clinical outcome in an individual patient, they are about the practical feasibility of the method. In other words, is it actually sufficiently easy for physicians to carry out and does it seem likely that it might produce good results in a larger cohort of patients.

    Although this is an “existing” technique, it has not been widely applied in the treatment of early stage, localized prostate cancer. All that this study would claim to demonstrate is that application of the technique to focal treatment of men with localized disease appears to be practical (and therefore potentially useful).

  6. I expect no randomized study will be done to evaluate focal therapy, which means we will never know if the treatment is really worth doing.

  7. Dear Gerry:

    What’s new? We have little to no evidence that any available treatment is actually worth doing in men with low-risk prostate cancer … but most (sexually active) patients would probably tell you that anything they can do to preserve their sexual function (if they are going to get treated) is worth trying!

  8. If sexual function is a priority for patients, which procedure (e.g., radiation, cryo, RALP, HIFU, etc.) has the best results in sparing the nerve bundles and how is success measured?

  9. Dear Elucidated1:

    Respectfully, that is not a very elucidated question.

    Even for patients who meet all of the criteria for low-risk disease, the answer still depends on that patient’s individual anatomy, the precise location and extent of his cancer, his PSA level and clinical stage at diagnosis, his PSA density, the skill of the person carrying out the specific technique used, etc., etc. Some of those factors may be unpredictable.

    No one technique has “the best” results, there are only levels of risk and those will vary based on the above factors. Furthermore, until we actually can tell whether a man with low-risk disease even needs treatment (which we can’t, as of today), it is (arguably) an irrelevant question, because it is trumped by a more important one: Is the individual patient’s priority elimination of his cancer or quality of his life?

  10. Of course my question is not elucidated. But that is the exact kind of question being asked every year by 240,000 newly diagnosed patients in the US and there are too many different answers. Even though the “everyone is different” argument is valid, physician competence and experience, as well as obsession to get it right also plays a large role in patient success.

    “Active surviellance” is the best choice with one tiny caveat: People who get cancer want to get rid of it right now. And if they don’t, their wife does. First, get rid of cancer. Second seems to be the issue of side effects. They don’t want to wait. Many feel it is just rolling the dice.

    So, how do patients deal psychologically with AS? What strategies are available? BTW, my apologies for the pretense of “elucidated” but that is my pseudonym for political writing. My real name is the same as yours.

  11. Dear Elucidated1:

    The question being asked every year by 240,000 newly diagnosed men and their family question is biased by some very false assumptions.

    With regard, very specifically to a diagnosis of prostate cancer, it is way past time that we all (1) began to stop “reacting” to the word “cancer”; (2) learned to seek out professional medical advisors who are also not “reacting” to the word “cancer”; (3) realized that the percentage of that 240,000 men who are going to die of their prostate cancer is now down to about 12%, and that even most of them will not die for another 10+ years.

    The entire way we think about the management of prostate cancer today is prejudiced by the assumption that every man so diagnosed has a “deadly” form of the disorder … and it isn’t even close to being the truth.

  12. Nice one. But just like any classroom, it’s up to the teacher to set the tone and get learning buy in. In the field of medicine, the word “cancer” has been successfully demonized way too much, and its use as a common metaphor seems to now compromise rational thought.

    The “professional medical advisors” you refer are part of the problem, in my opinion. As we’ve previously discussed, urologists continue to disagree with each other … so how the heck is a patient supposed to figure it out? The statement that the “management of prostate cancer is prejudiced by the assumption …” is certainly valid.

    It’s seems so easy to rationalize cancer and recommend watchful waiting for patients if you are a physician. But when it is you who has cancer and may not have the intellectual tools to deal with 10 different recommended treatments or the emotional fortitude to stay the course, knee jerk results happen.

    For professional credibility, I’d just like to see a 5-year data base of just 100 urologists who were diagnosed with prostate cancer themselves, the treatment choices they made and the rate of recurrence and side effects. Everyone seems to be an expert and know the proper treatment … until it is they who get the cancer … and gets to deal with concerned family members, friends and the inherrent fear of not knowing if the cancer will leave the prostate causing other issues along with ten different “recommended” treatments they really don’t understand.

  13. Elucidated1:

    This is a classic circular argument. Stop asking questions and seeking “data” and become an advocate for common sense — to your friends and your acquaintainces, to your doctors, and to anyone else you talk to! Smart patients are the greatest resource we have to encourage rational change.

    Oh … and actually I disagree with you. I happen to think the student has a high responsibility to set expectations in any educational setting, and to challenge the perceived standards whenever it seems appropriatre.

    Specialists today are as much victims of their training as patients are victims of the demonization of cancer. If you had spent 12 years training to become a urologic oncologist, and then practised as one for the next 12 years, don’t you think that you would tend to believe in the value iof surgery as a treatment for prostate cancer? Most of the surgeons I know who have been diagnosed with prostate cancer are completely convinced that the surgery they received was absolutely the best thing they could have had done. I don’t know many radiation oncologists who have had prostate cancer so I don’t know if they chose to have radiation therapy.

  14. Site, you are just a star in your acceptance of stupidity and a rational voice in this discussion.

    Right now, I am sitting at 7,800 feet in Tahoe, about to jump off the back deck, ski down to the lift at Heavenly … and try and get in 4 hours of cancer-free skiing before the SuperBowl. It’s been 9 months since my HIFU. I have no side effects. My family and friends are ebullient at my success. And I crank up my earphones, and drop in, I’m not going to look back. I hope every prostate cancer patient enjoys the success I’ve had. And the peace of mind.

  15. I would like to hear more on HIFU.

  16. Jim: Just enter HIFU into the search engine at the top of the blog.

  17. Jim,

    I can tell you my experience with HIFU if you e-mail me. I am not paid by anyone, am exactly 1 year out of HIFU, which had no pain and no side effects in my case. My PSA is now 0.3 ng/ml.

  18. I am a registered nurse and the wife of an otherwise healthy, 60 year-old-male who has recently been diagnosed with early prostate cancer (Gleason 7; stage T1c); have been to two urologists for consultations … had to “piss off” the first to get to the second as the 10-minute consultation left us both with many questions; can’t see a urologic oncologist here unless your disease has already metastasized; of course urologists want to do surgery … It’s their bread and butter and emotionally they cannot care about everyone they see. Patients and families need to advocate for themselves; do your research and don’t be afraid to ask the questions. Active surveillance is difficult, especially when you have a frame of reference of other family members who have suffered with the disease. How do you forget what that looks like? We will be contacting Ontario re the TULSA procedure. All procedures are risky but so is “living with cancer”. Our urologist describes it as “a crap shoot”. I also wonder what he would do if it were him?

  19. Dear “Other Half”:

    It is not yet clear to us whether the trial you refer to as the TULSA trial, which is now (apparently) open in London, Ontario, is based on the use of Insightec’s ExAblate technology or some other form of MRI-guided focused ultrasound methodology. It is also not clear whether this trial is only open to enrollment for men with low-risk disease (in which case, potentially, your husband may not meet the eligibility criteria since he has Gleason 7 disease, which would place him in the intermediate-risk category).

    As far as we are aware, only one patient has been treated on this protocol so far, and we have a lot of questions about the technology and the experience with its use in the treatment of localized prostate cancer. (All of which does not mean it may not be viable; we just recommend caution and lots of questions.)

  20. Dear “Other Half”:

    OK … We have found the outline of the trial protocol for the TULSA study. It uses a completely new technology that combines MRI guidance with focused ultyrasound (the so-called Prostate Ablation Device: PAD-105). This means that no one actually has much experience of the use of this technology in actual clinical practice.

    It will include men with Gleason 3 + 4 = 7 prostate cancer (but not Gleason 4 + 3 = 7) so long as the patients’ PSA levels are < 10 ng/ml. However, there are lost of exclusion criteria that you may want to review.

  21. Sorry, I stand corrected. His Gleason score is 6 in 1/12 core samples. Second TRUS 0/12 but PSA rising and last test 8.92 to 11.2. He also has chronic prostatitis and history of controlled ulcerative colitis on no meds. Not sure if UC would be exclusion criteria. Unable to have any radiation, brachytherapy, etc.

  22. Just read the exclusion criteria. … Rats!

  23. The trial protocol includes, as one of the exclusion criteria, “History of ulcerative colitis or other chronic inflammatory conditions affecting rectum.” This may or may not apply to your BF. However, if his latest PSA was “8.92 – 11.2” (and I am not sure exactly what you mean by that), that may in itself exclude him.

    My guess would be that at this very early stage of testing a very new device, your BF is not (sorry) going to meet the inclusion criteria for this trial for one reason or another. In Phase I trials of new technology like this, developers like to make absolutely sure that there are no extraneous reasons why anything would go wrong.

    Have you explored whether other forms of focal therapy might be appropriate (i.e., forms of treatment in which only the portion of the prostate that is actually cancerous gets treatment)? One of the reasons that your husband’s PSA is elevated is almost certainly because of his chronic prostatitis (as opposed to the prostate cancer).

  24. Other Half:

    It might help you to join our social network, where it is easier to get into a lot more detail (and where you can learn from the personal experiences of others too).

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