 Well, thanks so much Chris and Carrie for asking me back. Nice to see everybody this Saturday morning So I'll spend a little time going over the evaluation and then maybe we'll stop take some questions If there are any and then go over to the management portion most of what I'm going to focus on is really what we would call the clinical T1a renal mass or four centimeters or less But also some of the things I'll touch on are going to be for bigger localized tumors as well So in general when we do an evaluation one of the foundational things that we do is a history and physical This is just to look for signs and symptoms that may need additional workup to assess for overall health risk for anesthesia For example, what other medical conditions there are that may impact that the care in the treatment? We obtain blood work together. What's called a comprehensive metabolic panel? This includes checking the kidney function from which we can do a calculation called the GFR Which is a more precise way of measuring someone's kidney function and get a baseline for where that stands But also in the metabolic profile, we look for other secondary markers that may indicate the need to do other types of tests And then because kidney cancer has such a propensity to metastasize to the chest Chest imaging is a reflexive thing that we do either by chest x-ray or by CT scan depending on the scenario and then finally and much more relevant to what we're evaluating is Getting abdominal imaging to look at the kidney the tumor the opposite kidney and the adrenal glands lymph nodes liver, etc. And part of that is all the part of the assessment that we perform Typical questions that we get And this is very common for the three of us at least that you'll meet over the next hour or so myself Dr. Wood and Dr. Karam Do I need a bone scan? Do I need a brain scan? Well, these actually depend on a variety of factors Primarily in a case of localized disease. These are not considered to be routine they can actually believe it or not cause more problems than they can help in those settings because Quite commonly there can be little spots that really have no meaning But then we're obligated to follow those up and it also creates anxiety on the patient's part However, if we see anything on the history and physical or anything on the blood work that may indicate They need to do these tests then we would those are indications to do that Very common question is I want to get a pet scan or it's not a question. It's a demand and sometimes It's a question. Why aren't you doing a pet scan because I saw billboard on my way over that, you know, it's the best thing ever Actually as it turns out for kidney cancer, it is not for some cancers that are Consistently hyper metabolic where they use up a lot of glucose. It can be a good test for kidney cancer It has been well shown to really not be reliable So and of course, I'm not talking about scanning your pets But this is called a positron emission test or tomogram and what it might look like is something like this One of the problems with it is that the kidney and the bladder basically take up the injection That's given so it doesn't really help to show anything in the kidney Secondarily, however, the issue can be is that kidney cancers may be cold. They may not light up And they can be variable and if they if there's metastatic disease some of the metastases can light up and some of them may not So it really does not give you a confident assessment of what's going on the other thing that's kind of new to the United States not new in Europe or Canada but it was approved within the past year by the FDA is contrast enhanced ultrasound One of the issues that we have with imaging is that many times We can't give contrast because of kidney function being poor because we either taken out the kidney or the patient had bad kidney function to begin with So the nice thing about contrast enhanced ultrasound is that the injection doesn't really affect kidney function It's actually micro bubbles of carbon dioxide. So you may see on ultrasound something like this. It looks really fuzzy I can't see much of anything either except I know that this is part of the kidney here And there appears to be maybe something here, but really it's not very clear when they give the Micro bubble injection then it becomes very clear about what's going on in the kidney So we're all very excited about this opening up a whole new way of Imaging and maybe even helping our surveillance population avoid x-rays One of the major dilemmas that patients face and we face when we see them is the is the kidney function dilemma Unlike lizard tails and livers kidneys don't regenerate so That creates an issue for a patient who is faced with loss of a kidney or Who presents with? Already having declined kidney function due to heart disease vascular disease diabetes high blood pressure, etc In addition as we get older we lose kidney function And this is just a graph from one of the largest studies done that basically shows higher rates of bad kidney function as patients get older So it's an unfortunate fact of life if you add diseases such as diabetes and hypertension then this loss is accelerated And so there's a very strong link there between heart disease and kidney disease The other common question we get is why do I have to have contrast? I'll give you a couple of examples of how much this helps Here's a scan looking at a left kidney. There's clearly an abnormality here. It may be a cyst Maybe not could that be the problem actually when we give contrast what we see is that the kidney lights up pretty nicely The cyst does not it actually looks very similar if you look before and after contrast and there's actually a way of measuring the pixels here Which means there's no blood flow and if there's no blood flow There's really no concern on our part on the other hand suddenly what we see inside the kidney is This lesion that does have blood flow and this is suspicious for small kidney cancer in a very difficult location in the kidney There's another example non-contrast study of a left someone else's left kidney Something looks kind of funny here We scan in the early part of the contrast phase We actually can do it at multiple times because it gives us slightly different pictures and suddenly what? Appears is that maybe there's something here, but maybe there's actually something here And there's hardly any indication of it on non-contrast and then when we made a little longer and scan the patient again As it turns out this is a normal part of the kidney and the tumors actually right here So it can make a big difference in our assessment and planning and strategizing how we deliver care and also for follow-up And keep in mind that even with good contrast studies, it doesn't really help us differentiate to a large degree Whether tumors are benign or malignant and if they are malignant and suspicious for kidney cancer What particular type of kidney cancer as it turns out there's some subtleties and sometimes we can be suspicious of one Or the other based on some of these nuances, but it's still not definitive And so this is what they all may look like once we Send them to pathology and they start evaluating them And this slide is also here for me to remind you and you'll get more in-depth talks about this later That these are even though they arise from the kidney They're genetically actually very different types of tumors and they actually arise from different portions of the kidney But more about that later So I'm gonna stop in terms of evaluation. That was a very fast run-through about How we evaluate patient a patient with localized disease? I don't know if you all have any questions or if I just want to go on and maybe we can do some later Okay, all right so on to management a Few considerations again going back to the evaluation kidney function is of course a very important factor We not only want to look at the function in a patient who presents with two kidneys and a tumor in one kidney But what might that kidney function look like if we're considering removing that kidney, right? So we want to be able to think ahead a little bit the patient health and vitality their ability to tolerate general anesthesia and a potentially a major surgical procedure And part of that is they're competing medical risks I'll go over the treatment options if there's time We'll go over a clinical guide actually we will look at clinical guidelines if there's time we'll talk about surveillance So there's various organizations out there that have put out clinical guidelines the American urological association the National Comprehensive Cancer Network the European Association Keep in mind that we have very few randomized prospective studies in kidney cancer so the overwhelming majority of the data is actually based on Consensus meaning a bunch of experts getting together and fighting it out and The toughest and loudest one usually gets their voice but not necessarily sometimes it can be fairly democratic But it's based on low levels of what we consider to be scientific evidence and much more of a group empirical process if you will Also as a result keep in mind as why these are guidelines these are not set in stone and Different urologists and different practices based on their experience may modify these and that's okay The a ua guy the a way was probably one of the first that actually put out these guidelines I was lucky to be to participate in this back then and what we decided that based on the data We had at the time was that for a clinical T1 a tumor meaning one that's localized and less than four centimeters Either a partial or a radical could be considered standard standard is their definition really for their highest level of recommendation and that Surveillance or ablation which I'll talk to you more about in a few minutes Could be an option If their patient is healthy and an option is like the lowest level of recommendation And if they're not healthy someone who's kind of infirm or has medical issues then it could be an actual recommendation So it's a lot of wordsmithing here and you can imagine what the conversations look like behind closed doors Now then NCCN a few years later Gives preference to partial nephrectomy for these small tumors and a radical nephrectomy only if a partial is not feasible And then the rest of it is pretty similar the European guidelines Very similar to the NCCN in that they primarily recommend a partial for these small tumors and a radical if it's not suitable and in Elderly or sicker patients or someone who's older or has limited life expectancy some of these other options so now what we have In 2017 is really a large amount of a large degree of options for patients Now for a patient who has a bigger tumor or multiple tumors complete removal is still a reasonable option Although more and more in the correct setting will do a partial nephrectomy whether it's open or robotic And then for the smaller tumors percutaneous Ablation which means basically killing the tumor by heat or cold energy And then active surveillance and I'm gonna go in reverse order to talk about some of these options with you Before I do that I do want to spend a minute talking about the role of biopsy because it's a very common question that we get a common concern and as well something that To varying degrees we rely on in different settings more and more Historically, we've only done it if we were concerned that something had spread to the kidney If it was a lymphoma or someone with another cancer had a mass in their kidney And we worried we used to do that primarily for that reason because we didn't think it was reliable to tell us About whether it was kidney cancer or a benign tumor of the kidney But things have actually changed and now the accuracy of these biopsies has gotten much better And it's just to due to a combination of factors that I don't have time to get into But it's due to them being able to get a little bit more tissue reliably and safely and as well Pathology being able to do these special stains that can help differentiate these different types of tumors that To the naked eye under the microscope. They may look very similar So about greater than 80% accuracy currently with about a 10 to 15 percent chance of still not being diagnostic a Very common concern that we get is that biopsy spreads cancer We really do not see that in the contemporary period and again This is based on modern techniques that are used by interventional radiologists Now there are some limitations to the biopsy and some of this work was actually done by our fellow and with dr. Wood and actually helped really Define a little bit clearly the role of biopsy. It may not perfectly determine what kind of kidney cancer there is It's not bad. Maybe two to two out of three times. It'll be pretty accurate But when it comes to determining how aggressive that kidney cancer is You can't really rely on it too much for that If you just want to divide it as low-grade and high-grade for example Yes, two out of three times it may be correct if you're trying to determine exact rate Yeah, one out of three times maybe a little better than that and then in detecting sarcomatoid component really not very good most of the time So that's it really again just a quick glimpse of biopsy and its potential role So we'll go on to treatment options and we'll go from basically the least invasive or non-invasive To the more invasive ones So active surveillance actually represents the most non-invasive and the most kidney-preserving option there is and what this means is that we're gonna monitor the patient Actively we're going to get imaging studies to monitor the rate of the growth And at this point, this is something that's been done for over 20 years in a more rigorous fashion than it was in the past We have data from greater than a set thousand if not over 2,000 patients from international centers And what we've concluded is that it's a reasonable initial treatment option But for select patients those who are unfit they have what we call competing risks of death Bad heart disease bad lung disease Maybe they have another cancer Or some just don't want to have surgery It does require personalization and what we would call a risk-based approach But the patient also has to agree to follow up with imaging and that for me and my patients It's basically a verbal contract that we need to make sure we have an understanding about That i'm not saying that it's okay to completely ignore it and forget about it But that they do need to have it monitored and we do have cases Where patients have in fact done that and then come back and the tumor has grown and gotten to be problematic to treat but in The overwhelming majority of cases when these tumors are small and by small I mean less than three centimeters The average growth rate is actually quite low even when we know that they're kidney cancer So this shows what we call a waterfall graph And this is over the course of two years what tumor sizes have done These show tumors that have shrank The blank here that you see is actually tumors that did not change over the course of two years And even even if they even if they grew they grew minimal amounts with a small A minority that had more rapid growth and actually if we look at the initial tumor size of these These were actually larger tumors to begin with That on average about a 0.25 to 0.3 centimeters rate of growth in our series here So how often do they spread when we watch them? Does that happen? And there's actually several studies out there one of the more recent ones looked at 18 Basically pooled 18 other studies in 880 patients And two percent of these patients experienced metastases over the course of over three months And it was associated with larger tumors to begin with and those who had a faster growth rate So those you know that basically gives us some criteria to be able to tell patients look we can watch this But there's some risk because you have a larger tumor or we've been watching it. Look it's growing a bit more quickly There's some concern here. Maybe we should think about intervention So in our own population The metastatic potential is less than 1% out of roughly actually at this point about 380 patients that we've been surveying over the past 10 years. So it does happen, but very low probability of doing so Overwhelming majority of cases the delay to treatment if you do decide to Provide treatment at a future time doesn't appear to Limit the treatment options or and the tumor doesn't appear to progress basically again for the most part And the other thing that happens is that sometimes the tumor grows and the patient says oh my gosh It's probably cancer as it turns out. It's not the case We see benign tumors growing and we see kidney cancer is not growing So the fact that it grows or doesn't grow doesn't really tell us Which one it is and basically we still need tissue if we if we want confidence about which one Which one of these it might be So that's a again a quick glimpse at active surveillance Uh renal ablation is something that we used to do a lot more in the past It's still an option But to be quite honest with you with all the other great options we have I find myself offering it less and less to patients We can talk a little bit about that maybe during the answer during the q&a Reinal cry ablation has been around the longest Basically, this means we're going to freeze the tumor with these specialized probes that cause an ice ball Uh, they're actually the tumors are punctured by this probe and then they're frozen and then we thaw it and we freeze it again Uh, we used to do these laparoscopically now we do them mostly percutaneously through the skin Um, so this is an example of a kidney tumor before cryo ablation Afterward it actually looks bigger because we actually treat an area larger than the tumor to get a margin But the most important element at this point at one month Is that there should not be any blood flow? And in fact, you see a very sharp border between the blood flow in the kidney and the absence of blood flow in the cryo lesion At three months, we're still looking for absence of blood flow But what's happening now is that it's shrinking which is great And then at six months it gets even smaller by one year sometimes all you can see is just a small scar So that's the best case scenario Radio frequency ablation is the same idea it uses energy except now it uses radio frequencies to heat the water in the tissues to steaming levels and basically And even higher and basically cooks the tissue When we used to do these this is basically one of the probes it has these umbrellatimes that you can deploy once it's inside the tumor And basically as you'll see in the second there, it's just you'll see a lot of steam And all this vapor and it's basically essentially creating intense heat to destroy tumor it's a popular choice these days because The risk of bleeding with it is exceedingly low and especially when we're dealing with a lot of patients who have these Heart stents that requires them to be on blood thinners And we can't take them off for a long period of time and there's risk of bleeding That that's a good option This shows an example of a patient with a solitary kidney and a small tumor being treated percutaneously with the probe through the back And then same idea in terms of follow-up serial CT scans absence of blood flow and ideally a shrinking lesion over time I'm going to skip over some of this Overall kidney ablation is not bad When we did the analysis with the aua guidelines what we found was that it had 88 to 90 efficacy But that was in the short term And that doesn't look too bad But as i'm going to show you with partial removal the results are even better So what we tell patients is that look it's a good option if you're the right patient for it But the results may not be quite as good. There may be a higher risk of the cancer recurring in the area You still have the options of removing it or repeating ablation in those cases But it is something to keep in mind And of course since we're not taking the tissue out to confirm what it is We generally recommend a biopsy very strongly And sometimes even afterward if we have concerns about it being incompletely treated I'm going to skip over that So on to partial nephrectomy or partial removal of the kidney removing That part of the organ that has the tumor in it This is me operating with dr. Novak He was actually really one of the first to push this procedure back in the 90s and really helped establish it as a standard back in the day In the old days we used to make these huge incisions probably that surgery that I was doing It looked something like this About 25 years ago But doing it open is really the most established procedure It's been around for decades. We have the largest experience with it the longest follow-up of patients The downside is that there is a flank scar. It is a little bit of a longer hospitalization and recovery time These days really the incisions are not very big We've learned to really minimize these and we have these powerful local anesthetics where patients really don't have the pain that they used to Laparoscopic partial nephrectomy was really the first minimally invasive Extension of this procedure that was done. What we learned after several hundreds of patients and multiple institutions Is it was technically a bit difficult? It's a complex operation And as a result we noted that there was a slightly higher rate of complications with this procedure So what happened was is another extension of that was that this robotic surgical system came about And people started applying doing it with laparoscopic surgery And what this allows the surgeon to do is to do these complex maneuvers such as suturing in a much more easy fashion And i'll tell you a little bit more about that So for example an open approach is a very good option for very complicated tumors This is a tumor that's deep within the kidney You couldn't even see it if you exposed the whole kidney because it's completely inside These arrows show you some of the critical structures The blue is the interface of tumor with kidney. The yellow is where the urinary collecting system is Here's a different view showing tumor a little bit lobulated Urinary collecting system straddling it all the way out here These red arrows show all these critical arteries that are surrounding the tumor all of which we need to preserve if we're trying to preserve the kidney And this is a procedure that we would In the past generally would have done with open surgery Probably today might still consider it depending on the scenario But this just shows some of the intraocular pictures that were done Showing complete removal of the tumor in a bloodless field We actually have the kidney ice to preserve its kidney function while we have the blood vessels clamped And this is what it looks like with the blood flow reestablished And this is the complete removal of the kidney there and it's typical clear cell renal cell carcinoma This is a CT scan on the patient six years later without recurrence and a good functioning kidney So for very complex cases in solitary kidneys or patients who have multiple tumors in both kidneys such as those with von Hippel-Lindau syndrome This is a very reasonable option And remember I showed you the results with ablation about 88 90 percent in the short term with this procedure We believe it's 98 percent or better over the long term greater than five years So it's a very good cancer operation that preserves kidney function Increasingly we're actually doing a lot of these robotically But in a center where they don't have it or that they don't have as much technical experience I think an open partial is certainly a very reasonable approach certainly better than complete removal of the kidney for a small tumor You know rather than To do a complete removal rather than a partial would not be something that would consider reasonable And again the days of the huge flank incisions are pretty much gone So let me tell you a little bit about the robotic system for those of you who are not familiar It's basically two portions two components of it. There's what we call the surgeon console the surgeon sits separately from the patient Looks into the stereoscopic view that provides a three-dimensional image. He or she controls these instruments That go through the second component the instruments are actually through these four different arms They're at the bedside here And the tip of these are micro risted instruments So they basically basically replicate the wrist of the surgeon And whatever the surgeon is doing here The machine duplicates inside the patient So it really gives a great deal of flexibility and maneuverability where we did not have it before Through a minimally invasive procedure through these punctures The other aspect of this I don't really have time to go over with you but just Gives you an example here when we're doing a partial removal as a routine. We always do these ultrasounds And what this does is gives gives us a great picture of what's going on inside the kidney Before we cut, you know the old adage measure twice cut once. Yeah, we actually do that too sometimes three times But what we can do that with is with this ultrasound system Which is really great because it allows us to plan out And strategize exactly what we want to do and then in almost every case execute exactly what we had planned And so here this is a tumor that was completely inside the kidney But with the ultrasound I was able to see it Mark out the margins and then very confidently resect The tumor with negative margins So the advantage of the robotic system is that it replicates the open partial Minimally invasively But really what's more important than the machine you have to keep in mind is the surgeon's experience The machine does not work on its own. It doesn't have a brain. It basically just follows the surgeon's commands So a surgeon experience really still remains the most important aspect of it And then to finish up in terms of options radical nephrectomy What we mean by radical is that it's complete removal of the kidney All of its surrounding fat Part of the ureter Sometimes with the adrenal sometimes with surrounding lymph nodes that those do not have to be routinely done And it can either be done through open surgery or laparoscopically again depending on the surgeon's experience Although this is a pretty well established procedure at this point And sometimes it depends on the size of the tumor and a few other factors There's actually a randomized study one of the few ones that we have in kidney cancer that looked at Partial nephrectomy versus radical nephrectomy And unfortunately the bottom line is that it was not definitive because of a variety of reasons One of them being that they could not enroll enough patients Um, we could spend a whole hour or two arguing about how it was designed or how it could have been designed But the interesting thing was that actually most patients ended up dying of heart disease rather than kidney cancer and Um, really there's so many limitations that even the authors of the study didn't really believe the conclusions and They promote continued partial nephrectomy in patients The other question that we get is, you know, do you need to remove lymph glands? Um, there was another randomized study done in this scenario And similar to the prior one, there were some major design issues That prevented the ability for us to reach a definitive conclusion There's been a lot of studies in the literature some from ours a lot from the Mayo Clinic Also that maybe showed some benefit to removing lymph nodes There's a lot of selection biases involved in those types of studies Ultimately, I think the final, uh, uh, nail in the coffin, if you will, on this topic came out from the Mayo Clinic A very large study Uh, and ultimately they actually disproved their own data Which showed that removing lymph nodes generally really does not make a difference in the patient's survival It can add information about staging But for the large part doesn't seem to impact, uh, survival Um, I'm actually going to stop In the interest of time and the other speakers We can always talk about surveillance with the q and a if there is any questions that you have about that Basically follow-up after treatment, but I'm going to stop Any questions? I thought you had a question chris for a second. All right. No question. All right. Thank you all very much