Mark Emberton, BSc, MBBS, FRSC (Urol), MD, FMedSci: So, who is eligible for focal therapy? Well, it's an individual with an MRI lesion, that is clearly identifiable, from across the room. So, there's no doubt that there's cancer present. That is clinically significant. Most lesions are by the way. It's very, very rare for a lesion to have anything less than a gleason 3+4, around which you can get a margin, without damaging any key structures. And that's pretty much it, in terms of eligibility. Now, how you treat that lesion, if the lesions in the front part of a very large prostate, you won't reach it with high intensity focused ultrasound. So, despite the extraordinary flexibility that I get using the Sonoblate, I can't reach a lesion that's more than four centimeters beyond my focal point. Why? Because my focal point is four centimeters away from the probe. And so, in a large prostate with a very anterior lesion, I would use an interstitial treatment. And I currently would use electroporation. So, nanokinife which I use for lesions that I can't reach with high-intensity focus ultrasound. And so, there are broad criteria, which I've kind of listed earlier. And then there are specific criteria, which relate to the exact location of the tumor, and its proximity, and its context. By context, I mean if it's surrounded by calcification, which is very rare. Then obviously, you would not use ultrasound, because the sound waves wouldn't get into it. If the prostate was very small, you would struggle with cryotherapy, because cryotherapy creates a kind of an ice ball, which is a bit like ice- we call them Oreo, you might call them lollipops. I can't remember, in the US. And so, a very small prostate might be difficult to treat without damaging key structures, et cetera. And so, the expert user will be making an overall judgment about the suitability, and then a tactical judgment about what energy source, will serve this individual best.

So, to measure the dose received in focal therapy, so received by the host organ by the prostate or the tumor, is very hard to know. We know the dose that you expose the patient to. So, in other words, we know in HIFU the wattage that you gave to the prostate, we know in electroporation the voltage, that you gave to the prostate. But in the prostate, the impedance is changing, and therefore, the amps are changing. In HIFU, you are heating the tissue, and therefore, the tissue aeration is changing. And this is the judgment and the skill. I'm very fortunate with the Sonoblate system, that I'm allowed to use lots of user variability. So, I can determine, I can up the dose, I can retreat areas. I can change positioning. I can change the focal length. So, I have extraordinary flexibility about where I'm treating. And I also have some real-time feedback, which is the echo that's generated from the tissue after I treat, which gives me a very good sense of the degree to which I'm treating. I verify the treatment by doing a post-treatment MRI on all patients. Now, it's quite a luxury to do that because you have to do it quite early. You have to do it between day one and day seven, ideally. And that allows me to see exactly what I've done to the prostate, in terms of the error of necrosis. In other words, dead tissue or non-peruses tissue that you've generated. And that allows me to determine the margin, make sure there are no treatment complications, and allows me to tell the patient quite early on in near time, not real-time, in near time, that they've had- that I deem them to have had a successful treatment.