HIFU Expert: Cary N. Robertson, MD

Dr. Robertson is a urologic oncologist and Associate Professor, Division of Urology, Department of Surgery , Duke University Medical Center in Durham, North Carolina. He received his medical degree from Tulane University School of Medicine and was a Urologic Oncology fellow at the National Cancer Institute in Bethesda, Maryland. He has authored more than 100 published articles to date, lectured nationally and internationally, and held positions including the current president of the North Carolina Urological Association. Current areas of research interest include the associated immunological effects of HIFU on prostate cancer in vivo, and the clinical effectiveness of HIFU in human trials of localized prostate cancer. More information on Dr. Robertson can be found here and he can be reached at .

 

Robertson180Q: When and how did you get interested in focused ultrasound for the prostate?
My first real introduction to HIFU was around 2006 at the annual American Urological Association meeting. There was an investigator meeting there with EDAP, TMS, Inc. where the concepts of HIFU were discussed and an offer was made to participate in their upcoming clinical trial in localized prostate cancer. I had heard about HIFU tangentially as an up and coming technology but didn’t know a lot about it. I was fortunate to serve as the national Principal Investigator at Duke for this clinical trial, whose purpose was to the safety and effectiveness of HIFU as the initial treatment in men with newly diagnosed localized prostate cancer, compared to cryotherapy.

Q: Please describe the current nature and scope of your focused ultrasound research program for treating the prostate.
Sure, so I have been working with the Biomedical Engineering Department at Duke for about seven years now. Some of our past published works include survivorship in mice whose tumors were treated with mechanical dissociating HIFU [find/add link] -- which is similar to the University of Michigan work on histotripsy that you may be familiar with. We’ve also looked at immune modulators’ effect on treatment response, and published a manuscript looking at something called STAT 3 inhibition [add link]. Also, the checkpoint inhibition story in immunotherapy is a very hot topic right now, and we wanted to expand that into the basic science labs, so we are now exploring the same model that I just mentioned, but looking to use checkpoint inhibitors to modulate the immune response. We will also be monitoring immunologic markers, in combination with the immunotherapy team at the Cancer Institute at Duke; in that case we’re teaming with immunotherapists to look at the potential usefulness of HIFU. I do think HIFU can be a preparative treatment to enhance the immune response.

So I would say our preclinical models are our main focus of research. But we also believe there can be correlative science in any human trial, and so we’re working with the medical oncology research team at Duke to develop a line of investigation where we would monitor immunologic markers after HIFU and potentially have a therapeutic trial where we would have immunotherapy in combination with HIFU for the treatment of locally advanced prostate cancer. That’s a lengthy way of saying that our research effort is basic but it’s becoming clinical. And right now the only clinical trial with HIFU conducted at Duke was the registration trial with EDAP for the Ablatherm device that I mentioned earlier.

Q: What focused ultrasound system(s) do you use?
We used the Ablatherm device (EDAP, TMS, Inc.) in the clinical trial looking at low risk, low grade localized prostate cancer; we enrolled 27 patients at Duke and 135 nationwide. That efficacy data has been submitted to the AUA in abstract form and will hopefully get accepted and presented publicly in Spring 2016. Now that the Ablatherm device has received approval, we’re hoping to bring this device for clinical use to Duke.

Q: Any thoughts on watchful waiting/active surveillance versus treatment with HIFU for men with prostate cancer?
We routinely recommend surgery or radiation for patients with intermediate risk disease; those men would not be put on watchful waiting or active surveillance, unless they have really low volume disease. I think the sweet spot is intermediate risk disease. If we see a candidate with a clean MRI, even with a positive biopsy, and a Gleason score of maybe 6 or low grade 7, we can tell them they’re a good candidate for active surveillance – those are not the patients I think we’re looking at to enroll in HIFU treatment. While this recommendation hasn’t yet been formalized, I would say that the thought among the international community and leaders in the field is that the intermediate risk (Gleason 7) patients are the most appropriate potential candidates for HIFU.

Q: What can you tell us about focal treatment versus whole gland HIFU?
I think we’re going to be seeing whole gland HIFU for patients with small gland, low volume, Gleason 7 disease. And keep in mind that there certainly may be fewer side effects with hemi-ablation/focal HIFU compared to other treatments, but that is not the case for whole gland HIFU. Trial data showed that only 25% of whole gland HIFU patients completely recovered erections back to their baseline – and you see those same rates with surgery as well. Whole gland HIFU also treats the urethra so patients may temporarily stricture their urethra (15%) and may need some kind of secondary management like a catheter or dilation. But if you perform a pre-HIFU resection of the prostate (TURP) in advance and open up the bladder and the urethra a bit, they don’t have this problem as often.

For perspective, whole gland HIFU in Europe has been practiced in about 5% of prostate cancer patients, and Ablatherm is in 90% of HIFU sites, but there is limited experience with focal treatment. So I’d estimate that initially 90% of patients will be offered whole gland treatment and probably 10% will get focal treatment. That will change as data on focal therapy becomes more mature. If I had a male relative 55-60 years old, with a unilateral ½ cc lesion on MRI in the posterior lobe of the prostate, and everything else is clean, and biopsy confirms Gleason 7 pathology, I think I might advise focal therapy for that prostate as opposed to whole gland. It may better preserve erectile function and urinary control, with less risk to the urethra.

Q: How does FUS/HIFU fit into Duke's overall prostate program? What percentage of patients get FUS treatment compared to other approaches? Is this changing? How many patients have you/Duke treated with focused ultrasound for the prostate?
We treated 27 patients at Duke between 2007 and 2010 under the ENLIGHT Ablatherm clinical trial. I would say that HIFU fits in our overall program of GU cancer care as a new option for treatment, utilizing a multidisciplinary approach to patient evaluation. We have a combined clinic with medical oncology, radiation oncology and urologic oncology within the Duke Cancer Institute. We are having strategic planning meetings currently to develop an algorithm for new patient referrals which will expand our multidisciplinary clinics and incorporate HIFU eligibility determination at the time patients are referred for localized prostate cancer. So while no patients currently receive HIFU treatment at Duke, that’s in development and will likely change. My prediction is that we’d expect 10-20% of new patients with prostate cancer to be eligible for HIFU, either whole gland or focal.

Q: Can you share some thoughts about what the FDA approvals of SonaCare’s and EDAP’s HIFU systems mean for men with prostate disease in the US?
HIFU is an additional option for therapy that I believe is unique and potentially transformative – and by “transformative” I mean that it is a new approach to prostate tissue without tissue disruption. I think HIFU ablation is very interesting because it doesn’t involve a lot of pain, discomfort, or inconvenience. It’s an ambulatory treatment which is well tolerated. In that regard it’s also very different than the other treatments which need needles, catheters, surgeries, etc. Of the invasive treatments currently available, HIFU is the least invasive. External beam radiation therapy is obviously the least invasive as it is “touchless.”

Q: Where do you think FUS should fit in the treatment of prostate cancer?
I think HIFU has great potential. It can be used for localized disease, either whole gland or focal treatment, and it can be used as immunopreparative therapy for advanced disease or metastatic disease theoretically – and that remains to be proven as a good strategy. But it has the potential to be able to treat prostate cancer in many stages. I have a great feeling that in the future we may see HIFU transition from less of only tumoricidal thermal treatment and also of a tissue disruptive/preparative treatment.

Remember, over 40,000 prostate HIFU treatments have been completed worldwide and results are published demonstrating long term outcomes similar to alternative, more established therapies. The role for HIFU will continue to evolve as more experience is gained in various clinical settings.

Q: What do you think about the potential role of the Focused Ultrasound Foundation in advancing the technology for prostate treatment?
There is a strong track record of using forums, symposia, etc. to bring people together, even newsletters and just sharing general information on cross-disciplinary approaches. Your biannual symposium is excellent for this, and I should know as I’ve attended three symposia over the years! I think having the HIFU users in GU learn about how HIFU is being used in neurosurgery and how it’s being used overall, for example, increases the general awareness and acceptance of the technology. I personally find it fascinating to learn about HIFU and treatments for bone cancer, pain alleviation, Parkinson’s tremor, etc. I also think the general community is very large and we urologists tend to stay very focused, with blinders on if you will – and so having FUSF inform the group and maybe help create a stronger identity within the urologic oncology field would be very beneficial. We need a community of urologists who are interested in HIFU, and I think HIFU users around the country will need to form a working group and communicate, perhaps with the Foundation’s help.

Q: Anything else you would like to add?
I’m fascinated by the fact that when the prostate is treated with HIFU there is a significant decrease in tissue volume – 20 ccs will shrink to 5 ccs on average. It implies in my mind that there’s a real treatment effect on the tissue with HIFU. And it’s also remarkable how HIFU is really not uncomfortable, and is very well tolerated. There is minimal pain for the patient.

I would add that any procedure has risk. HIFU is not a no-risk procedure. I think it’s much, much better to say that for very selected patients I think HIFU can be an ideal alternative to more aggressive, traditional treatment. I think it’s really important to look at patient selection and let that dominate as we proceed with HIFU in the US and elsewhere for prostate treatment. Keep in mind, too, that it’s early and we’ll gain experience over time, and there will continue to be advances in HIFU devices as well. And I personally am excited to continue exploring the potential immunologic benefit for HIFU patients that is currently under study. It’s a very exciting time.

 

 

     

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