Focal Therapy - Art Rastinehad

May 26, 2019

Art Rastinehad provides insight into the role of focal therapy in the treatment of prostate cancer.  He begins the presentation with the evolution of prostate cancer care.  He describes focal therapy in the context of the next significant opportunity in the treatment of prostate cancer once we have a positive biopsy and walks us through the why, the who the how and the where in defining focal therapy.  Thank you for John Fortin who created this presentation for use on UroToday with Dr. Rastinehad.


Art Rastinehad, DO, Director, Focal Therapy and Interventional Urologic Oncology Associate Professor of Urology and Radiology, The Mount Sinai Hospital Mount Sinai St. Luke's and Mount Sinai West Mount Sinai Beth Israel.  Ardeshir (Art) Rastinehad, D.O. joined the faculty from the National Cancer Institute as an Interventional Urologic Oncologist specializing in the surgical management of prostate, kidney, adrenal, and testicular cancer. Dr. Rastinehad has expertise in a wide array of interventional radiological and surgical techniques, including image-guided procedures, laparoscopic and robotic surgery. He has a faculty appointment in the Department of Radiology and Urology.guided procedures, laparoscopic and robotic surgery.
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John Fortin: Welcome to AUA 2019. With me is Dr. Art Rastinehad who's agreed to discuss the presentation he made on prostate cancer focal treatments. Thank you so much for making time to do this interview. With your experience in both urology and imaging, you bring to today's discussion a uniquely informed perspective. 

Art Rastinehad: Thank you so much for having me today. It's a pleasure to be here. I believe focal therapy is a topic that should be discussed on a regular basis and investigated as we move forward with these new therapies that are being developed today. 

The evolution of prostate cancer care has been very exciting since 1853 when Dr. Adams described the first case of prostate cancer in London. The next advance with Dr. Hugh Hampton Young describing a perineal prostatectomy, followed by a urologist winning the Nobel Prize for medicine, 1941 Dr. Huggins describing the impact of androgen deprivation on prostate cancer. 

Then in 1980s, the advent of PSA, new TRUS biopsy needles, and Dr. Walsh's contemporary description of radical prostatectomies led the way for advances in prostate cancer care. It wasn't until 2009 when Dr. Pinto and Wood at the NIH released the first FDA approved MRI ultrasound fusion guided biopsy device. I'm here today to discuss the focal therapies and the next step forward in the evolution of prostate cancer care.

With all patients, once they have a biopsy, the question arises, if you can see it and you biopsied it, why can't you just treat it? I'll discuss today the why, the who, the how and the where. 

First the why. Over diagnosis and over treatment of prostate cancer is a real issue patients and urologists face every day. Besides the risks associated with radical therapies, the morbidity and mortality, the sexual and urinary side effects are worrisome to patients. 

The solution may be an outpatient same day treatment. It has lower risks of sexual urinary side effects. In some cases, no Foley catheter is used. Looking at the evidence, it is limited at this time. We're looking at durability in cancer control, and focal therapy is still considered investigational. 

The majority of low risk cases are treated radically. Looking at the information we have, 50 to 75% of men with low risk prostate cancer can choose active surveillance upfront. However, historically up to 60% of patients could cross-over to active therapy or radical therapy, and this data is similar to data observed in the ProtecT trial. 

Taking a different look at how this is evolving, who could be candidates for focal therapy? The University College London, Dr. Ahmed looked at a case of a hundred consecutive prostatectomies, examining patients for focal therapy criteria. They found that up to 51% of patients that were treated radically could have been candidates for focal therapy. 

Our understanding of focal therapy has evolved over the last 10 years. Our typical inclusion criteria used to be patients only Gleason 3 + 4, and PSA is less than 15. This has been increased to include patients with PSAs up to 20, up to T2a disease, and all Gleason 7. They must have a life expectancy greater than 10 years and any prostate volume. 

It's important as physician scientists to look at our primary outcomes. Our goal is ablation of clinically significant disease and with imaging and biopsy, confirming that there's no cancer present at one year are important metrics that we're looking at.

To get patients in the urologic idea of what the current landscape is, a survey from urologic oncology evaluated 484 urologists and their thoughts on different types of cases that could be eligible for focal therapy. There is some heterogeneity of who believes patients could be focal candidates. However, one specific case stands out. That's a case of a man that's 69 years old, with a life expectancy of about 15 to 20 years. A PSA of 7.1 and focal Gleason 7, 0.5cc lesion, without any disease seen in other areas of the prostate. 

Looking at the how, how are we going to get there today? The entire paradigm of prostate cancer screen is being shifted. For example, the European Association of Urology recently updated its guidelines to say that patients should have an MRI before their first biopsy. If they have an ongoing suspicion of PSA, it's no longer viable for men with elevated PSAs to go straight to TRUS biopsies. We have other options. 

These include risk calculators, biomarkers and as I said before, multiparametric MRI of the prostate. The benefit of using imaging allows for targeting or improved sampling of the prostate to overcome the current limitations associated with a standard TRUS biopsy. 

What's the impact of the guided biopsy and biomarkers? Well, in 2010, there was less than 10 centers in the world that could achieve high quality multiparametric MRI imaging of the prostate. It's currently becoming the standard of care across the world, and it's causing this paradigm shift. Typically when we did a standard TRUS biopsy, 70% of the cases where low grade. 

Now, with the use of imaging and selecting higher risk patients, a majority of high grade disease we are able to actually visualize the prostate cancer that we're sampling. I don't know if anyone's really aware, but prostate cancer is the last solid organ malignancy in the human body that imaging does not play a major role in its diagnosis. The EAU has supported this, but other organizations have been slow to adopt a look first approach to screening and evaluating men at risk of prostate cancer. 

How do we follow these patients? The Focal Therapy Society, and multiple consensus panels in conjunction with the group, we have looked at this question. Typically we follow patients with interval PSA every three months for the first year, imaging at six months and at 12 months. At 12 months, there should be a confirmatory biopsy confirming if there's been no residual disease and/or demonstrating successful ablation of the prostate lesion in question. 

We do look at these outcomes. So do we observe with that information that was obtained at that biopsy? Do they need re-treatment, or will they have to be moved on to a more aggressive or whole gland therapy? After you've done this initial one year assessment, we typically follow patients with PSA and imaging and only biopsy if there's an increased suspicion of prostate cancer. 

A recent group published their information on TOOKAD versus active surveillance and the impact it had on patients with low risk prostate cancer. This team of researchers demonstrated that TOOKAD or VTP decrease cross-over to radical treatment in their group up to 30%. Therefore, if these patients were treated a lower probability of ongoing going onto radical therapies.

Where does focal therapy fit into the paradigm? Breaking down patients into very low risk, low risk, and intermediate risk prostate cancer are areas that we're looking at for focal therapies. High risk prostate cancer today is currently treated by radical therapies. Our initial paradigm we've pushed forward is, patients that are candidates for active surveillance should stay on active surveillance, and other ones will be pushed to radical therapies. 

Having the focal paradigm, we're looking to shift the group of patients that were previously treated with radical therapies to possible focal therapy. This is a form of cancer control. We can treat the visualized lesions and then follow these over time, and these patients hopefully avoid moving on to radical therapies, and I think that's what's really exciting about what we're doing. 

Another question people need to understand is, as we have this paradigm shift in how we screen, we're going to be identifying more patients with high grade disease because MRI is great at seeing high grade, high volume disease and misses the low grade, low volume disease that we really don't want to treat. So, this may lead the way in the future to more candidates being selected for focal therapies. 

Speaking of selecting candidates for focal therapy, it is important to understand that patients must have a standard biopsy approach as well as a targeted biopsy approach to hopefully decrease screen failures as we call them. Areas of the prostate where non-visualized prostate cancer was detected. 

Finally, who should be considered to focal therapy and how? A recent consensus panel from the Focal Therapy Meeting in Japan in 2019, we demonstrated that this should be biopsy confirmed, image-visible lesions with clinically significant prostate cancer defined as greater than Gleason 7, may be used as targets for focal therapy. This does leave the door open for possible treating high grade patients that have focal lesions with focal therapy. 

How do we do it? We do it with biomarkers, MR Imaging, and targeted biopsy, and it's really important as surgeon scientists as we evaluate this new technology, patients must have confirmation biopsy of ablation at one year. This is something that the FDA has asked us to look into to confirm that we're actually able to ablate the areas that we have identified that are prostate cancer. Finally, the last who in the conversation should be physicians, and they should be looking at this new technology and evaluating critically with current trials. 

I'd like to say thank you for allowing me to discuss my talk and my topic today. It's very exciting to be here. I believe focal therapy is the middle way to hopefully identify men and give men an option to avoid radical therapies and their associated side effects. 

John Fortin: Thank you, Art. That was great. If I may, I would like to ask a few questions. First, in your opinion, based on a patient's MRI, his Gleason score, his emotional tolerance, and other factors, if a patient is a really good candidate for active surveillance, should he also consider focal treatment? 

Art Rastinehad: No. In one word, I think if you're a good candidate for active surveillance, that's probably the best way to move forward. We're still following you, keeping a close eye on you with imaging. If something does change, we have multiple options including focal therapy to address any treatments if needed in the future. 

John Fortin: That was very clear, I appreciate that. Second, I know this is a new area and so we are struggling with it, endpoints might make sense to really judge success. There's probably a disconnect, some patients who knows what they expect, but from your point of view, what is the success after focal treatment, what do you look at? 

Art Rastinehad: I kind of, I like to break down my success in two categories. One, the specific outcomes from a clinical trial that we look at. What's the success in the ablation zone? What is the metastasis-free survival? These are the metrics we're looking at, and this is what the FDA looks at when evaluating a trial. 

But when we look at the patient, it's, what morbidity do they suffer? Do they have an improved quality of life without undergoing the therapies that would have been recommended in the past? And more or less their overall wellbeing. Are they happy with the treatment they've received? 

John Fortin: I want to be an optimist, but let's face it, there is a chance of recurrence and I guess that applies to any treatment. If a focal treatment has evidence of disease afterwards, how do we do the re-treatment? You've touched on this already, but I'd like some more clarity in that topic. 

Art Rastinehad: I think first you have to just even take a look at the terminology. One's salvage versus re-treatment. Salvage therapies have higher risks of urinary incontinence, lower success rates. And then you compare that to re-treatment. Some focal therapies don't burn any bridges. I've done research with gold, silicon, and anode shells. Post therapy, there's less fibrosis around the outside of the gland. 

This allows you for options that even include a radical prostatectomy, but really what's exciting about focal, there is a new lesion or recurrent lesion and still within the prostate, there's so many options available to patients that we can retreat these patients, taking into account their current clinical variables, their overall health, and how they feel about what options they have that are presented to them. But I think focal therapy re-treatment is an option that we are pursuing and investigating. 

John Fortin: Dr. Rastinehad, your presentation is just superb, was extremely clear, insightful and provocative. Thank you so much. 

Art Rastinehad: It was a pleasure to be here. Thank you.