 I'm Karen Konoski and welcome to this month's edition of kidney cancer news. You know, I'll kind of start with the topic that's last on that list in regard to why we want to preserve kidneys. And this is something that's coming under increasing attention both by physicians, urologists and also patients are starting to become a little bit more aware about this. So part of the rationale for preserving kidney function wherever we can and whenever we can is that we're finding out that the outcomes from a cancer perspective are the same for up to certain size tumors and certain locations. So we've known for many years now that tumors up to four centimeters have the same outcome whether you take out the whole kidney or just part of the kidney. And as it turns out in some cases even bigger tumors depending on where they are. We also are coming to the realization that anytime we see a tumor in the kidney it does not always mean that it has to be cancer. The odds unfortunately are against us and that usually it is cancer. But there's particular groups, particularly women for example who are in their forties who have about twice the chance of having a benign tumor. Now as it turns out those odds are still against those women because it's still about a 60 to 70 percent chance of it being renal cell carcinoma. But nevertheless it's an important thing to keep in mind. But then there's another important factor and actually it's kind of warm up here if y'all don't mind I'm going to take my jacket off. Anybody else who wants to do that? And what we're finding out is that having kidney disease has an impact on one's survival and one's life. Now just to be clear when I talk about kidney disease I'm not talking about kidney cancer okay these are two separate issues. One can have a disease of the kidneys where the kidneys don't function well. And that's a separate issue than having a tumor or a cancer of the kidney. But obviously as you all probably know there's an important interplay and you can't think of one without thinking of the other during the treatment. So what we're finding out is just having kidney disease can have an impact on survival. And they're just taking out kidneys for small tumors can in fact alter that survival for patients not from a cancer perspective but from a disease perspective and I'll show you some of that data. So how do we define this? Well there's a measurement that we can make based on the age the gender and the blood levels of creatinine and that's called a GFR glomerular filtration rate it's also called a clearance. So less than 60 is defined as having some kidney disease normally somewhere around between 80 and 120. Now as it turns out you know when we're born we have way more kidneys than we need okay we have an abundance of kidney function but as we get older we lose it. We lose it by process of aging we lose it if we lose it even more quickly if we develop high blood pressure particularly if it's uncontrolled, diabetes, smoking. All these poor lifestyle choices that go on particularly in our society really accelerate the loss of kidney function. And as it turns out having kidney disease is a predictor of developing heart disease. So you see all these things are kind of interrelated. Just to show you an example of how prevalent this is, in fact maybe what I'll do is I'll use the mouse because I think that will be better visible on the web but this is actually one of the largest population studies done looking at kidney function and kidney disease in the United States population. And what you can see is that as we get older the rates of kidney disease go up but if you add to that high blood pressure and I apologize for all the medical jargon here but high pretension or high blood pressure, diabetes or if there's a family history that's this pink group that then you have rates of about 60 percent and particularly in the age groups where we tend to see kidney cancer. So again a lot of this sometimes is related to lifestyle decisions that we make throughout our lives and then suddenly decades or many years later we realize that those lifestyle decisions have put us at a disadvantage. So the important time to really think about it is to pass it on to the younger generation and make sure that they started hearing to those lifestyle decisions. So in that light partial kidney removal starts making a little bit more sense and this is just a diagram showing you some of the classic techniques that are used what we call a wedge resection where we can wedge out the tumor with a margin of normal kidney or just cut off the proportions of a kidney etc. And this is what it might look like for real. This is a classic looking clear cell renal cell carcinoma. This is a small tumor probably about two centimeters in size maybe a little bit less than an inch and here's the normal kidney tissue that's around it. As it turns out it doesn't really matter how big this margin is as long as there's a margin treatment of the renal tumors is fine as long as you have something there. And this is what we call the reference standard of the gold standard. And if we look at all the publications published that show survival and how good this operation is as it turns out is it's exceedingly good 98 percent or better efficacy at greater than five years. Now clearly there probably is some link to experience of the surgeon because this is an operation that's in the community some are still not completely comfortable with it particularly if the tumor is in a difficult location. But nevertheless this is a very successful operation in these cases when it's a small tumor. Now it's true that there are some complications with it as there are with any major operation but typically bleeding and leakage of urine from inside the kidney are the two that we particularly worry about. And I put the urinary leak in parentheses because quite honestly in our practice at least I can tell you we rarely see that and I think probably nationally you know as a specialty I don't think we're seeing it as much only because I think our techniques have gotten so much better. So it's particularly a really good option for kidneys situations where we want to do hypothermia that's when we actually ice the kidney down because we're worried about it losing function during surgery because we do have to stop the blood supply temporarily while we're cutting it out. Or if we're trying to do it without cutting off the blood supply. Or if it's a very complicated removal and we need to work quickly. Now having said that there are some newer minimally invasive techniques that we're doing for smaller tumors where we can do this less invasively and still get a very good outcome you know trying to achieve that 98% efficacy. And a robotic or which is a laparoscopic procedure a robotic partial nephrectomy is really the next evolution of that. And this is this doing the same procedure but in a minimally invasive fashion. Now I'll just show you an example of an open operation. So this is actually a patient 63 year old who basically had this is the left kidney here it was a non functioning kidney very poorly functioning you can see how small it is compared to this one. But this one as it turns out her good kidney actually has a pretty good size tumor in it and this is in a fairly difficult location the artery to the kidney is right here and it's involving looks like it's involving the where the urine collects which is this darker material here. And so the goal here was preserving this kidney while still doing an optimal cancer operation. And so this is what it might look like during surgery you actually just see the edge of the tumor here there's a margin of normal tissue and again this is done through an incision on the side here through a flank incision. And what we have here is again is the tumor normal margin. This is normal kidney all in here. This is actually where the urine collects and drips down into the bladder. And what we have is essentially a successful removal and as it turns out this was a benign tumor. The patient did perfectly well and her kidney function was essentially unchanged after one year. So again that's a very successful operation but clearly there are some downsides to it the recovery time and the pain from the incision being really the one thing that has prompted us to develop these less invasive techniques. And so we can try to achieve some of those same outcomes without making an incision but instead making small punctures and putting in a scope long instruments. And we used to do that laparoscopically which means basically controlling the instruments directly with our hands. But there's newer technologies that have come about which some of you may know about one of them is the robotic instrument. And this is what it looks like. Basically the surgeon sits at a console and then there's a second, the actual robotic machine itself, mimics the hand motions of the surgeon. What the surgeon is looking at is a three dimensional view of inside the body because one of these arms holds a scope. And then these miniaturized instruments have this dexterity and miniaturization that allows it to work inside the body through these small incisions. And so this is, I'll show you a partial removal that's done robotically. What we're doing here is actually stopping the blood supply into the kidney. That's a clamp that's put on the renal artery. That's the inflow of blood to the kidney. And another one on the vein. And what this allows us to do is to remove the tumor in a bloodless field so we can actually see what we're cutting through. That's really the important part of the operation. And this video is actually sped up a little bit, okay? I wish I could work that fast. But what we have here is actually what you're looking at is fat over the tumor. You don't see the tumor. That's what a good cancer operation is. You don't actually want to see the tumor if you can help it. We've preserved the fat over the tumor itself. I had marked out where I wanted to cut. And what we're cutting through now is kidney. And I'm making sure before every cut that we don't have to see anything that's suspicious. And if there is, I would adjust and cut somewhere differently and go deeper if I need to. Here, we're looking at it to make sure. And you see there's minimal bleeding because we've stopped the blood supply. And now we're gonna suture. There's a bunch of blood vessels here that are gonna bleed once we unclamp. So we wanna suture them to prevent bleeding after surgery. And that's basically what we're doing. So what you're seeing here is all these instruments are being controlled by the surgeon sitting at the console. Occasionally, you'll see a little suction instrument come forward. And that's the assistant at the bedside who is controlling that. Okay, let's move forward for time. So that kind of covers in a very summary fashion partial removal. The other thing that I wanted to talk about was the role of ablation. And this is a treatment that you all may hear about or come across. This is when we use energy to kill cancer without having to remove it and subject the patient to surgery. Every energy source that you can imagine has been tried. Cold is called cryoblation. If you try to free something. Heat, it turns out it's a lot easier to generate heat than cold. So there's multiple ways that we can do that. You can use electrical radio frequencies. You can use sound. That's called high intensity focused ultrasound. Same way that they can do shockwave of the kidney. You can actually alter those frequencies and have it break up tissue. Lasers can be used, which is basically light and that can generate heat. You can combine light and a chemical and that's called photodynamic therapy. And then there's an idea now of using focused radiation therapy. But all of these I'll tell you are experimental with the exception of the cryoblation and the radio frequency ablation. These have been used for over 10 years and they are pretty well integrated into most centers that treat kidney cancer. All these other ones are highly experimental and unproven, okay? And I'm not really gonna talk about them. And so in general, what we're talking about here is the difference in terms of removal versus ablation. When we do traditional surgery to remove a tumor, we remove it. It goes to the pathologist. They can look at it under the microscope, do all their chemical stains and then come back and tell us, yeah, you got it all. This is what it looks like. It's a clear cell or it's a papillary. It's grade three, et cetera. Well, we don't really do that with ablation, right? And so we want to, we're treating it, we're killing it and we're leaving it in place. And so what we're completely reliant on at this time is scans. We need the scan beforehand to know that we're accurately targeting where the tumor is and then we need scans afterward to make sure that once the treatment is done, that the area is fully dead. And that's when things get a little controversial. So in order, since we're not removing the whole tumor, we need biopsies. We have to have some idea of what we're treating. I mean, there are going to be some patients with these small tumors that turns out they're benign. Maybe we don't even need to treat it because it's a benign tumor. And then there's a role possibly for biopsies even afterwards and I'll talk a little bit about that because I know the issue of biopsies is always one that's on patients' minds. So I just want to briefly cover cryoablation and radiofrequency ablation. With cryoablation, basically what we do is use these specialized probes and inside these probes are actually tiny channels that allow passage of specialized gases like argon. And there's a particular physics law but I'm not going to bore you with that. But in essence, if you pressurize the gas and suddenly release the pressure, it gets really cold and that's how they're able to form these ice balls at their tip. So it requires puncturing the tumor, turning on the gas and then you get this ice ball that essentially kills all the tissue inside it. And this can be done percutaneously through the skin or it can be done laparoscopically. So it gets pretty cold. It's about minus 150 degrees near the center and close to about minus 40 degrees at its periphery. This is what it might look like if we do it laparoscopically. What you're seeing here is actually two views. This is the laparoscopic view. Here's the tumor and I know the resolution isn't great, I apologize. What you saw there was an ultrasound probe which you see here and this is the ultrasound view from that probe. This is the cryoablation probe itself and you can see ice starting to form because we just turned on the gas. We've already punctured the tumor and then we can actually monitor what's going on under ultrasound and as that ice ball gets bigger, what you see here, we're just gonna do a picture and picture and flip it. You can see how it just forms a snowball. Excuse me, this is like snow cone. And again, we can just monitor that treatment with ultrasound and ensure that we got complete treatment. And then afterward we patch the patient up, they go home the next day and then one month after treatment, this is basically what it looks like beforehand but one month after treatment, we're not seeing any enhancement. You see how the kidneys are kind of white from the IV injection of contrast but there's no enhancement in this area meaning there's no blood flow. At three months we start seeing it get smaller and then at six months even smaller. That's the ideal situation, no enhancement and shrinkage or involution as we call it over time. So the other way to do it is with heat as I told you that's with radiofrequency ablation. There's a variety of different types of probes on the market and again here the idea is to heat the tissue up and try to kill all that tissue. And again, it can be done percutaneously such as shown in this example, this is a patient who actually has only one kidney, small tumor that was under observation but was growing and this patient wanted it treated. So while the patient is asleep, at this point he is sleeping on his abdomen and this probe is passed through the skin and into the tumor and then treated that way. And again, if we do it laparoscopically this is what it might look like. Here's the tumor itself, we puncture it and then you deploy those umbrella looking tines. That's what delivers all the radiofrequencies and then you can see it starts smoking, right? And that's what you're doing is you're heating it up and that's actually not smoke, it's steam. So this is the same thing. Afterward, at one month the area is treated, there's no enhancement and over time ideally what we can see is no enhancement and shrinkage over the lesion. So what's important to know about ablation is that the efficacy is not quite as good as surgery. And when these first came out there was great promise. You know, suddenly we thought, hey maybe we can stop operating on everybody and treat everybody with these. But as it turns out it's not quite the case. If you remember on the previous slide for partial removal I showed you 98% or better, right? Greater than five years. Well there's not even that much five year follow up on these treatments. So in a shorter time interval it's less effective. It's not bad still, 88, 90% but still not as good as surgery. So for that reason we reserve it for the sicker patients, for the elderly or if they have a lot of medical conditions and we're worried about the anesthesia risk. These days we deal a lot with patients with these stents in the heart where they can't come off blood thinners and so they're at pretty high risk for surgery and bleeding. And so the advantage of these treatments is that the overall complication rate is really pretty low. I mean there are complications, there always are. You know, we work very hard to minimize them but you can't eliminate. But as it turns out in terms of serious complications it's a pretty low event for these procedures. And that's why we reserve it. You know that the lower efficacy is balanced by the fact that there's a little bit lower risk profile. The one thing, the one contract I make with my patients though is that they have to accept the biopsy ahead of time so we know what we're treating. To do the imaging at our center because a lot of radiologists who aren't familiar with the treatment or don't know what's happened to the patient will read scans like that as being concerning for progressive cancer. So you can imagine the anxiety that causes for the patient. And I've been through that enough times with these anxious phone calls and emergency plane flights here that I said, you know what? We just need to do all your scans here. And what we've learned because of that lower efficacy rate is that we probably should do biopsies six months to 12 months after in cases when there's any question. So a couple of comments about biopsy. And Chris, were you gonna cover this at some point? No, perfect, good. So in general, when you talk to most urologists still they'll say they don't wanna biopsy a tumor of the kidney because it won't change the decision factor and the results aren't very good. But I'll tell you things have changed dramatically in the past three to five years. It's changed rapidly enough that it's not in the textbooks really. You know, anything you read in the textbooks is at least about five years old by the time it's printed. So the results are markedly improved. Part of it has to do with the technique that the interventional radiologists are doing to get actual tissue. And part of it is on the pathology side where they've discovered ways of staining these tissues where it can be much more informative and they can give a confident diagnosis about what this tumor is. Is it kidney cancer or isn't it? And if it is kidney cancer, what kind of kidney cancer is it, right? So that's kind of what we've been aiming toward finding out and they are getting better. It's still not perfect. There's still about a 10 to 15% chance of it being non-diagnostic of not really finding out one way or another. So biopsy is still not something we do routinely because, for example, a younger patient with a tumor in the kidney that's of concern, we're not gonna ablate it. We're probably not gonna watch it and I'll talk about active surveillance in a minute. We're gonna operate because we're not gonna take that chance. So in that situation it probably doesn't make sense to biopsy. But for these other situations that I covered with you in terms of ablation, for example, we definitely wanna have some idea of what we're treating. So I think that kind of covers that. The other question actually that comes up with biopsies that's very frequent and I know Chris and I both get asked this pretty much every time we're in clinic is this gonna spill my cancer? And probably it is something that used to happen many years ago when techniques maybe were pretty crude. We do, I would dare say, hundreds of biopsies at this institution probably on a weekly basis, maybe monthly. And you really never see that. And again, part of that is technique related and it's the way they specialize needles within a needle that they use. So really that's not really a risk. Bleeding is a risk of course anytime you stick a needle into anything. And so I'm actually gonna skip this but the idea here is the role of biopsies after doing a blade of therapy because there are cases when we're finding residual cancer even when the scans are negative. And so the sobering truth is that imaging is not as good as we'd like it to be. It's pretty darn good, it's better than it ever was but it's still not perfect. And so things on biopsy that we can learn for example are what the tumor grade is. Patients sometimes have a hard time understanding what grade is because it's not the stage and what I describe it as is sort of a measure of its potential aggressiveness. How mischievous is this gonna be if we leave it alone? Grade one, we don't think two mischievous. Grade three, four, yeah, it's gonna be pretty mischievous. And then there's different types of kidney cancer. These are all genetically different diseases. They just happen to all occur in the kidney as it turns out, clear cell is the most common type. But then there's all these other types and you know what, they all behave a little bit differently. And for those of us who treat a lot of kidney cancer you kinda learn the nuances of that and we do try to individualize our treatments based on these. And again on biopsy that might have implications for whether even we're gonna treat you or not. Okay, so lastly I wanna close with active surveillance and another term that we use for that is watchful waiting. And part of the reason this has become more popular, and again here we're talking about small tumors that are incidentally detected, is that we're finding out that patients aren't necessarily dying of these small tumors. This is a graph that I think is nice and simple and it kinda conveys in general what the idea here is. But if you take patients with a small tumor and see what happens to them over time, over the course of five to 10 years, most of the deaths occur for reasons other than cancer. These are things like heart disease, the number one killer. Heart disease is also the number one killer of cancer survivors, it's not cancer. So you can see how dramatically higher this yellow line is compared to the blue line and that's the kidney cancer death. And this is other cancer death. We're not talking about big tumors here. We're not talking about the big tumors that require surgery. We're talking about the small tumors that are incidentally detected, particularly in the older population. And then if you look at the older population in general, those who undergo different types of surgery or active surveillance, and this is a little bit of a busy slide, but what I'll summarize for you in general is that again in these patients the cardiovascular death rate is higher than the cancer death rate. So if we kinda keep all of this in mind, in addition to the fact that there's data now that shows that these tumors grow very slowly, what we're finding out is this may be a reasonable option in some patients. This is a study that put together all bunch of different studies that looked at how quickly these tumors grow. And over the course of, let's see, three years roughly about here, tumors grow about 0.25 to 0.45 centimeters per year, fairly slow growth. Now there are some that may grow more quickly, but in general most of them grow fairly slowly. This is actually data from 117 patients at our center we put together about a year and a half ago. Kind of a busy slide, but this literally is the measurements from every single patient showing you at the beginning when we started following them and afterward, you can see some kinda grow quickly. Some actually get smaller, weird, huh? But overall they all tend to have a fairly slow growth rate. So the fact that they grow, that they grow, does that predict the likelihood of cancer? And as it turns out, no, because cancers may not grow and benign tumors may grow. And this is another study that showed the compared tumors that didn't grow that were watched versus those that did grow and the incidence of cancer was the same in both. Well, is there a risk? You know, is there a risk by not doing anything and leaving alone these small kidney tumors? And for the majority of patients the answer is probably no. This is a study from Foxtase Cancer Center, 124 patients under active surveillance. 50 of them underwent delayed treatment, either because the patient got concerned or the tumor grew faster than they wanted to see. And most of the patients had kidney cancer, excuse me, kidney preserving surgery, that's what that means. They were still able to preserve their kidneys and still have treatment. In our own population, 117 patients under active surveillance, only 6% underwent delayed surgery, again, because somebody got nervous or the tumor grew faster than we liked. The other thing I'll tell you that's not on here is twice as many patients during that same time interval died of other conditions. So we saved those patients probably unnecessary treatment. But then nearly all of these patients underwent some kind of kidney preserving surgery if they did undergo surgery. And the bottom line here is that if you delay treatment for someone with a small renal mass, it doesn't really seem to limit their options or risk the cancer spreading. And this is what this shows is that of multiple publications, about at that time in 2006, 331 patients, three or less than 1% developed metastases were spread and become incurable. And in almost all those cases, it was tumors that were not really ideal for surveillance. These are tumors less than three centimeters. Once they get bigger than the risk of metastatic progression does go up. So the other thing I want to kind of close up with and I think I'm running out of time anyway, but the American Neurological Association convened a guidelines panel and I was honored to serve on that. But what they did was look at all the literature that's out there and do a meta analysis. It's basically a very complicated statistical study of everything that's published. And they came up with certain recommendations. And just so you understand what these different recommendations are, if they say something is standard, it means that the health outcomes are well understood that we can make meaningful decisions and there was virtual unanimity among the expert panel. Something is recommended if it's kind of, we kind of understand what the outcomes are and understand these things to make meaningful decisions, but there's not unanimous agreement about it. And something is an option if there really isn't enough data yet and the preferences in terms of these options are equivocal. Just to let you know, there was 11 panelists, several consultants, extensive meta analysis was done and then this went out to multiple other experts in the field, even outside urology, to review it. So it's a peer reviewed document and it's actually accessible to the general public. It's on the AUA website and I put it here for your information if you wanna access it. But this is, and it's an extensive document, but on one page it kind of gives you this example of three different, excuse me, four different index patients and what kind of tumors they have and what kind of treatments may be either standard or options or recommended. But you can see that in every situation, PN or partial nephrectomy, partial removal is pretty much the standard recommended treatment with the exception that for the larger tumors, that's what we call a T1B, a radical nephrectomy, complete removal may be indicated. Thank you all. Join us again next month for another edition of kidney cancer news. I'm Keri Konoski, wishing you good health.