 Morning everybody. It's really great to see such a fantastic turnout and to see a lot of old friends and get a chance to talk to you guys today about surveillance. So the idea of talking about surveillance is in part because we feel like this is an area of a lot of uncertainty for patients. So patients get their treatment, whatever it may be, surgery, ablation, and then they always wonder what next? Is that compressed? Does it look weird? It is in presenter mode. Let me exit that and just do that. Is that better? It's okay? All right. Let me try one thing. Is it making the computer? It's got a narrow format. Okay. That's pretty cool. Awesome. Thank you so much. That's great. Thank you so much and so that kind of core question of what next is I think really a confusing and daunting situation that a lot of people face. So I want to talk a little bit about how we treat treated kidney cancer and as part of it you know surveillance has a little bit of a double name in kidney cancer. One thing that we're using a lot more for localized kidney cancer is active surveillance. So someone has a tumor it hasn't been treated and we're going to follow it. So I'm going to talk a little bit about that. I also want to just obligatorily talk about kind of new things that are on the horizon for the surgical management of kidney cancer. So some things that we've been able to take advantage of locally as we try to stay on top of state-of-the-art surgical management of kidney cancer and then I'll focus on how we follow up patients who've been treated and how we follow up patients who have not yet been treated but we're watching their tumors very closely. This is sort of an algorithm that I talk about when we talk about how we surgically manage kidney cancer and so any of you who've seen me in clinic you know I always talk about how we have sort of this algorithm for how we think about the correct surgical management of kidney cancer. So someone has a mass and when we think about how to treat that mass the first decision that we need to think about is does it need to be treated at all. Some patients come in and they have a small tumor there's some uncertainty whether that's even a cancerous tumor and so there are some occasions where we can actually follow that tumor. I always think about how we want to balance the characteristics of our patients and the characteristics of our tumor and so someone who has maybe a lot of health problems and maybe has a small tumor we can watch that tumor because the risks of the tumor are not as great as the risks of their other health problems but someone who comes in who's younger and has that same small tumor we're going to intrinsically be a lot more aggressive. So that first decision should we do something or not that's not a no-brainer and so we spend a little time thinking about that. The next question we come to is well gosh if we're going to do something and we're going to do some form of surgery is this something where we can just take the tumor out and what we call a partial nephrectomy or do we have to take the whole kidney out. So I used to say I'm older than I look but now I think I'm probably just as old as I look and so but I used to say back when I trained laparoscopy was relatively new and so we saw a lot of doctors who are prioritizing a laparoscopic surgery over preserving as much kidney as we could and that's not the right order the first decision should be can we save some of the kidney and just take out the tumor and the area around the tumor or do we have to take out the whole kidney so that's the next decision and then the decision after that is well gosh can we do this with minimally invasive techniques that's actually that I couldn't find a good picture to use for the incision so I had to take a picture of my own abs to use for the to use for the to use for the slide so I'm sorry if that's too much information but in all sincerity as we think about you know what to do there are some patients that need an open operation and open operations for kidney cancer hurt because we're either making a flank incision that intrinsically goes through three muscle layers or making an incision under the rib cage that also goes through three muscle layers so if we can we try to do this minimally invasive either laparoscopically or robotically in a way where we can help you with your convalescence we want to prioritize being safe we want to prioritize doing good cancer surgery but if we can we also want to prioritize your quality of life so where are some things changing and some things benefiting the contemporary surgical care of kidney cancer patients well one we're able to make smaller incisions so we have newer robots that use smaller instrumentation which requires smaller incisions and sometimes that allows us to get away with fewer incisions and so there's like there's this idea that your pain from a surgical incision is exponentially related to the length of the longest incision so it's not a minor thing to have an 8 millimeter incision instead of a 12 millimeter incision so that helps our patients recover more quickly get back to work more quickly and those are important outcomes we have better access to tumors in difficult locations and I want to use that term difficult locations in a couple different ways one way is anatomically so where the tumor is located relative to the anatomy of the kidney and also difficult in terms of what other things that patient has been through past surgical procedures you know some patients come to us and they've had numerous prior abdominal operations some people come to us and they need surgery right underneath a stoma from a prior bowel operation and so difficult locations means both relative to the kidney as well as relative to the patient and then we're also learning that we can have better ability to delineate the tumor relative to the kidney around the tumor using some new techniques that are a lot more cost-effective today than they were even three or four years ago and that relates to our new surgical instrumentation and so this is our new XI robot we have had an XI robot for about three months and you can see with the XI robot we're able to make 8 millimeter incisions this is a patient getting what's called a retroperitoneal partial nephrectomy so this is where we go in behind the kidney create a space behind the kidney and this allows us to access tumors on the backside of the kidney and we're able to get away with four small incisions instead of one big incision that goes through the flank musculature and this is with the robot in place and so one of the thing about the robot now is because the arms are so much smaller there's less clashing of the arms and so we have a lot more mobility to work in tight spaces so it enhances our ability to offer patients robotic surgery whereas three four or five years ago we might offer them open surgery so it enhances our ability to offer surgery that we think is associated with better recovery it also allows us to access things in tough locations so I mentioned tough locations relative to the kidney I'll show you that in a second but also tough locations relative to the patient so this is a patient that had had their bladder removed and had a new bladder made out of colon on the right side of their belly and so their colon bladder sits right in front of their kidney and that kidney has a tumor in it right here that is super duper challenging but we can actually create a space instead of going this way we can create a space behind the kidney and I'll show you that in a second to access that same tumor without the morbidity of trying to manage that colon pouch and this is just a tough location so this is the tumor right here the blood vessels are going to go into and out of the kidney right here and so by creating a space behind the kidney instead of trying to work this way and go all the way around to the back it allows us to access these tough anatomic locations as well what this is doing is this is emboldening our ability to offer surgery to patients who for example have had over 10 prior surgeries for Crohn's disease or patients who like I showed you before have had a prior stoma in the same area as the surgery that we're going to offer and instead of going anywhere near this incision we can go off to the side and go behind and so we're able to save that patient from yet another big incision so this is just showing you a video and I want to show you this just to orient you to what we do in a partial infractomy and that's going to help you understand some of the cool things I'm going to show you with this new technique called the firefly so this is a video that just shows you the partial nephrectomy on that patient with a colon pouch and I want to highlight a couple things in theory there we go so this shows us creating a window around the artery that takes blood to and from the kidney and that's important because we're going to temporarily interrupt the blood flow through the kidney why do we want to do that well number one is for safety we don't want it to bleed when we cut into the kidney and number two is to see well if we're going to do a precise dissection of someone's tumor from the normal kidney we want to see as we cut in so this is showing you the kidney tumor right here and the normal kidney around it and now we're creating a line of incision in the normal kidney around the tumor so that as we cut into the tumor we've already created our line of incision now we're going to put a clamp on the artery and that's going to interrupt the blood flow to the artery so you can see two clamps including the blood flow to the artery and this is temporary and now we're going to cut out the tumor so we're coming underneath the tumor and you can see those are what we call cold scissors we're not burning anything and we're using cold scissors so we can see very precisely now what is really neat about this operation is you don't see this person's colon pouch this is right behind this gentleman's colon pouch and we never saw it at all during the surgery so it was a way to be safe and also afford him an operation that allowed him to get away with really small incisions we're going to burn the base and just close up the hole and it'll look like we've never been there before so it's like a ninja operation on the kidney so what about so what I showed you what I didn't show you in that video is that we used a little bit of an ultrasound device to show you the edges of the tumor what about new techniques that maybe help us do an even better job of that so if I want to take out someone's tumor in a rim of normal tissue I want to define that rim as accurately as possible because I don't want to create an incision line and accidentally cut into the tumor as I'm going deep into the substance of the kidney there's this technique called firefly which uses this fluorescent dye endocyanin green this endocyanin green binds to albumin which is a protein that circulates through our blood vessels and so it illuminates blood and so there are occasions where there is less blood flow in a kidney tumor than in the rest of the kidney around it so the kidney can light up as a bright green thing whereas the tumor is much darker or dark gray so you can see the margins of it and I'm going to show you an example of this that is sort of a hyperbolic example but it's a cool way for us to be able to see things better now this is going to show you firefly of the artery and it shows you that we can even use it to help us find the blood vessels to and from the kidney and this was important on this patient because this patient had an abnormal relationship between the vein from the kidney and the artery to the kidney where the vein was actually pretty far back because of the way the vein drained back into the vein that takes blood back to the heart so let me see if this this works here so this is showing you can see that we have nice green healthy kidney tissue underneath where we cut out the tumor so it allows us sorry about the background noise it allows us to see the edges of what we're cutting so that we can be safer and at the same time do better cancer surgery so it's pretty cool stuff so what about surveillance well and a question I get all the time when I see patients a couple weeks after surgery we're going over the pathology and it's what next and I think this is going to transition really well to Dr. Kite Tycote's talk about adjuvant treatment but we know that most recurrences after kidney cancer treatment occur within two years of the surgery there are certain sites within the body where kidney cancer is more likely to come back the lungs and chest being the most common sight that it comes back and it's confusing as a patient because if you look to the Internet you might see some guidelines from the National Comprehensive Cancer Network some guidelines from the AUA which is our urology organization some guidelines from international organizations and it can be very confusing to know number one how frequently should you get scanned how long should you get scanned for and that's all very confusing and I'm not here to answer those conundrums I'm here to sort of tell you about them and tell you about how we think about them and so this is a compilation and I don't expect you to read all these lines this is a compilation of guidelines from American urology organizations cancer organizations and international urology organizations and it shows you some common themes where you can see that in general for a lower risk kidney cancer we think that maybe about once a year we should be evaluating patients often with imaging studies like cat scans ultrasounds possibly MRIs and you're going to see a lot more exes on this next page this is for higher risk kidney cancers that have been removed and now you see that people are recommended to have evaluations every six months or so and what you maybe can't appreciate is that a lot of those evaluations involve CAT scans MRIs things like that one of the guidelines that is frequently used by payers are the NCCN guidelines and so one of the things that we confront as a care provider is trying to advocate for surveillance for our patients and that can be really challenging so I have to do a lot of appeals and peer-to-peer conversations with payers to try to advocate for my patients to get CAT scans and it's in part because of guidelines like the NCCN which we are a part of as a cancer center and so if you look at the NCCN guidelines for low-risk patients it recommends that you get some kind of imaging within about a year of surgery and thereafter it's fairly discretionary but they've changed these guidelines in the last two years to say that in general we should cease routine imaging follow-up at about three years so this is for someone with a small kidney tumor we've done something like a partial nephrectomy or even taking the whole kidney out and in general we're going to follow that patient up for about three years for a more aggressive kidney cancer we're talking about more intensive imaging usually every three to six months and we're going to continue that more intensive imaging schedule for about three years so if you're trying to figure out you know how often should I be seen how often should I be getting a CAT scan if you're a lower risk patient in general we tend to get a CAT scan about a year out from surgery and then another one about three years out from surgery and then we have a discussion about what to do next if you're a higher risk patient someone with a stage 2 or a stage 3 kidney cancer we're doing more frequent x-rays usually CAT scans about every six months and we continue that semi-annual schedule for about three years and that's not me right we do that for about five years so again at five years we kind of don't know what to do this is something that we have to clarify with insurance companies a lot but also more importantly with our own imaging centers so if we order a CT the abdomen a lot of imaging centers reflexively change that to a CT the abdomen and pelvis that means that you get charged for two CAT scans a CT the abdomen and a CT the pelvis but there's really no role for pelvic imaging in kidney cancer unless there's something else found like something in the bones of the pelvis or the hips or something like that but for routine follow-up of cancer that's confined to the kidney we don't really have an indication for looking at the pelvis a question that we get all the time from patients is about PET scans so I don't know how many of you have questions about PET scans but we hear a lot about how a PET scan is this total body survey that allows us to look for cancer deposits throughout the body but in kidney cancer it's a little bit different kidney cancer is not as metabolically active as some other cancers and so there's no real difference or added what we call specificity of a PET scan over a regular CAT scan so we do not routinely use PET scans in kidney cancer care so what about after three years or after five years and what this is showing you is this is showing you high-risk patients and how many years it would take to capture 90% of recurrences in the abdomen, chest, bones or other parts of the body how many years it would take you to follow patients to capture 95% of recurrences and how many years it would take you to capture a hundred percent of recurrences and this is not meant to say that kidney cancer can come back at any time remember this is 90% so this means that our five years of follow-up is capturing the overwhelming majority of recurrent cancer cases but if we stop following everybody at five years we're missing up to about a third of recurrent cancer cases so once we get to that five-year standpoint we always have a discussion with the patient about what we would hope our future follow-up schedule would look like and also what warning signs might be that would prompt you to have an earlier evaluation or an earlier surveillance imaging study. This is another way to look at this data this is a way to look at this data that shows you the risk of your kidney cancer coming back relative to your risk of other health problems being more important and a greater priority in thinking about that ultimate outcome of survival and if we look at this yellow line these are patients with stage 2 kidney cancers so that's a kidney cancer that is greater than seven centimeters in size but is confined to the meat or substance of the kidney and these different circles are for a patient who's 50 years old a patient who's in their 60s a patient who's in their 70s and what you don't see on here is a patient who's in their 80s and it's the number of years it takes your risk of your kidney cancer to surpass your risk of other health problems so you can see for a young individual 50 to 59 the risk of the kidney cancer is going to outweigh the risk of other health problems in almost all circumstances but as our patients get older into their 60s 70s and what we don't see out here as 80s the risk of these other health problems can be as or more important than the risk of the kidney cancer itself and so that makes us think about the role even for some larger masses of active surveillance so as we think about surveillance after treatment a couple quick notes you know these guidelines are important and they're important to know because these guidelines influence payer decisions about how we are able to follow up your cancers and so it's really important that we stay engaged with the current state of the guidelines in kidney cancer care for low risk patients those guidelines recommend three years of follow-up and even for higher risk patients those guidelines go out to about five years but there are the there is the potential that we might miss some recurrent cancer cases by stopping surveillance at that five-year endpoint so what is active surveillance so active surveillance is this concept that not all kidney tumors need to be treated and it's very hard because we personalize our own experiences with our own kidney cancers but the most common type of kidney tumor that is diagnosed today is a tumor that is less than four centimeters and that rate is is rapidly increasing and a big reason it's increasing is what's called incidental detection so it's not that the cancer itself produced any symptoms that prompted it to be detected it's that someone got a CAT scan for an unrelated problem like an appendicitis or something else and that CAT scan revealed a tumor on the kidney and most of these asymptomatic incidentally discovered tumors are actually small these small kidney tumors that some of which are kidney cancers have a very low risk of a bad cancer specific outcome so tumors that are less than four centimeters and even more so tumors that are less than two centimeters have a very low risk of something bad happening related to that tumor some of these tumors are benign and in fact that risk is much higher if the tumor is less than two centimeters and the patient is a woman under 50 where that risk of it being a benign tumor might be as high as 40% emphasizing the role of active surveillance in these patients because surgery for kidney cancer is not minor surgery it's not removing a lump on your shoulder and the rates of growth of these small renal masses are fairly slow at most about five millimeters per year so even if it grew even if it proved itself to be a cancer nothing bad is going to happen in that interval while we're watching so active surveillance conceptually we think is a very safe thing to do and I'm going to show you some data that really demonstrates that there was a systematic review of some single institution retrospective data so this is people that are looking back at their own experience and saying well gosh I watched a bunch of these patients how did they actually do and so of 24 published series which includes almost 2,000 patients with reasonable follow-up of two or more years the risk of a bad cancer outcome of one of these small tumors causing death from kidney cancer is zero the rate of it spreading to another part of the body in that interim is only 1% but other things happen other health conditions intervene so 10% of these patients had other health events that led to to deaths while they were watched what about the use of active surveillance we're probably not using it enough so when we look at nationally representative data on the surgical care that we're delivering for kidney cancer you can see in this red bar we're doing more partial nephrectomies that's probably a good thing if you looked 10 years ago fewer than 30% of patients with a small kidney tumor we're getting partial nephrectomies so that meant a lot of patients were losing their whole kidney for a tumor where we think we probably could have saved a lot of the substance of that kidney why is that important well dr. Musinski is going to talk about the differences in outcomes for renal function related to loss of kidney units and if you lose kidney function that can also affect other parts of your health like your cardiovascular health so prioritizing partial nephrectomy for these small tumors is really important but what you see on this gray dotted line is stable use for small tumors of active surveillance of only about 25% and we don't know what the right number is here is the right number 50% is the right number 70% I don't know but we should probably be using more active surveillance and so what we need is we need data that convinces providers that it's safe and it's not just providers that are our audience here it's also patients we need data that can convince patients that it's safe so this is the disarm registry which has a very cool acronym stands for delayed intervention or surveillance for small renal masses this is housed at Johns Hopkins and it's a prospective study so they are enrolling patients in a study with a dedicated surveillance plan and I'm going to show you their algorithm for it it's a little bit muddy but it's a multi-center study where they're following patients and their main outcome they're looking at is five year cancer specific survival so at five years did anything bad from a cancer standpoint happen to those patients if they were either treated with an ablative treatment or they had surgery versus those that just had their tumors watch they're now up to this isn't in their paper but this was in a presentation at G.U. Askel this year they're up to over 600 patients about half in half either got surgery or ablation or got active surveillance so it's pretty much an even split between aggressive treatment and active surveillance they have follow-up for that for the entire population of about three years but a third of the cohort actually already has five years of follow-up and you can see just like the retrospective data cancer specific survival is outstanding. Patients with small kidney tumors are very safely watched because nothing bad is going to happen related to the kidney cancer. The risk of progressing on active surveillance is about 25 percent so a hundred minus 76 percent and that progression means rapid growth so more than a half centimeter a year or an increase in size to above four centimeters so that happened to about 25 percent of the patients but their growth rate was actually very low it was only about a millimeter per year and one thing that's very confusing is these kidney tumors don't grow like this they kind of grow like this and one of those big jumps seems to always happen within the first year of watching it which also happens to correspond with the period of the most intense anxiety about your new kidney tumor diagnosis and so one of our jobs is to assuage patient concerns about periods of interval growth and maybe what we do in those periods is do a shorter term follow-up to reassess these tumors rather than reflexively putting someone through surgery who may not or may never need it. So this is their algorithm so they're taking patients with small renal masses found on a CT or an MRI and the patients are either going to get active surveillance or they're going to get intervention it's not randomized the patients choose this this is a patient choice clinical trial and we just watch and see what happens so they're enrolled into disarm and they either get surveillance or intervention and they get these serial studies now one of the core elements of disarm is that they actually follow all of these patients with ultrasounds and I'm going to show you one of our ultrasound images here we talked about how we define progression and these are the endpoints so they have cancer specific endpoints overall survival endpoints and they're also capturing quality of life on all these patients so what is the role of percutaneous renal biopsy and then I'll be done well we actually are big believers in percutaneous renal biopsy the old dictum and there's a lot of what I would say is misinformation about the role of biopsy especially in small tumors the old dictum was that if you did a biopsy and it showed cancer you were going to take it out anyway if you did a biopsy and it didn't show cancer you still are suspicious so you're going to take it out anyway so the biopsy didn't show you anything but what's different about biopsies in 2017 are number one our ability to target tumors so our imaging is better our access techniques to conduct biopsies are better so our ability to actually acquire a good piece of tissue on a biopsy is so much better than it used to be and then number two our ability to make diagnoses based on small amounts of tissue is also much much better so the accuracy of biopsies in 2017 is much better than the accuracy of biopsies in 2007 and that greatly enhances our ability to use a biopsy to make informed decisions with our patients who are trying to figure out what to do the next thing I want to talk about renal ultrasound so this is something we're very excited about because one of the things that can be difficult on an ultrasound is delineating accurately the size of the mass but also the internal characteristics of the mass and so what this is is a contrast enhanced ultrasound and you see the non-contrast image on the left and the contrast enhanced image on the right and the contrast is really kind of a contrast because they're micro bubbles and they cluster in small basically small capillaries and it creates an image that allows for the detection of enhancement and so that allows us to look at for example a kidney cyst and determine if it's a complex kidney cyst so we're using more and more of this contrast renal ultrasonography in active surveillance for our kidney tumor patients so just to summarize active surveillance for small renal masses that's all I'm talking about right now is very safe it appears that if we treat it or if we watch it as long as it's a small mass the cancer specific outcomes at least in the short term appear to be the same but we do need to this is why this term active is important we do need to watch patients we need to monitor these cysts or solid masses and preferably with ultrasound and then the other thing is and I didn't mention this before but the actual absolute size of the mass may be a more important determinant of how bad it is than the growth rate of the mass so I think we've been able to show that we have some new techniques available that allow us to offer I think safer better cancer surgery specifically with attention to small tumors when those tumors have been treated surveillance after kidney cancer surgery requires some format interval imaging the duration of that the intensity of that it's definitely it merits a discussion with your provider the guidelines can be confusing about that but for lower risk tumors maybe less imaging is required and for higher risk tumors maybe more intensive imaging is required for those tumors that we deem susceptible to simple follow-up that we don't have to be aggressive about and and do surgery for active surveillance for these tumors is very safe and gives cancer specific and quality of life outcomes that are on par with surgery thank you very much so I wait till later for questions do we know wait just because I'm right at time yeah so that may happen someday you know there was a big thing back in what the early 2000s when we're doing the executive CTs the early 2000s there used to be you would see billboards for this these they called them executive CTs where you go in you pay out of pocket and get a full-body scan and we actually got a lot of new detections of renal masses that way there is the the risk of finding things that don't need to be found on those scans and it can lead to unnecessary biopsies unnecessary imaging studies so it's not a no-brainer just to scan everybody because sometimes we find things that don't need to be found so it's a balance but I wouldn't be surprised if sometime in the next 10 years we are doing these kind of routine executive CT scans they were very popular for a while and we've kind of gone away from them but it's it's a good question insurance pay for them no yeah finding things so that's a much better more deliberate way of saying finding things that don't need to be found you'd rather find them yeah I mean before surgery or after surgery we so we have not incorporated that upstream of surgical decision-making that would require a biopsy are you thinking about like a liquid biopsy based on a blood test that is not yet ready for prime time we have a test locally available where we can take a kidney mass biopsy and try to understand its genomic genetic risk for having a aggressive features and sometimes we can use that information to make a decision for example to take the whole kidney out instead of taking out just the mass I will say that's the arena where I most often use biopsy is I think a mass has certain aggressive features it might be technically anatomically eligible for a partial nephrectomy but I'm trying to figure out gosh is that even the right thing to do and so a biopsy augmented by some of those techniques I think is really helpful I know it's probably impossible to provide a specific answer so or even a general answer but in your experience what do you think about the efficacy of treating a mass with chemo first shrink it down and then partial to me yeah so there was a our wealth of knowledge about that is related to single institution neo-adjuvant studies and so what that means is we don't think that the cancer has spread to other parts of the body but we're going to give you a treatment to shrink it and potentially treat microscopic deposits where the cancer has gone somewhere else what we found is that the ability of these treatments like suit and to shrink the main tumor is not as robust as you think it is one of the things that Dr. Tycote and I experience in our mutual patients sometimes is that these extra kidney deposits in the lungs or other parts of the body are responding really well but the main tumor in the kidney is not so I would never I would never be excessively hopeful with the patient that we were going to be able to do that it definitely happens we definitely see the tumors shrink but the rate of shrinkage of greater than 25% occurs in fewer than one-third of patients so robust shrinkage does not happen a lot yeah way less so the our most robust knowledge about this before this disarm study related to patients with kidney cancer syndromes like Vaughan Hippolyndale and we know that in those patients when their tumors were less than three centimeters in size their risk of it spreading to other parts of the body was zero and so what we started doing was watching those patients until those tumors got to be about that threshold size from the disarm study fewer than 1% of patients had spread of their kidney cancer to other parts of the body while they were on surveillance so the risk of one of these small tumors spreading to other parts of the body is very very low so this is a common misconception that there is sort of like a program that we implement on the robot to do the surgery the robot is a translation of our movements so we sit at a console with what are functionally joysticks and when I move like this the robotic arm moves like this so everything that you're seeing on those videos with the scissors are translations of my movements on a console to the movements in the body I'm not worried about it being hacked I'm not worried about it becoming self-aware yeah yeah and I'm also in the room I'm not hitting a button and going to get a cup of coffee yeah so that is they've always been done percutaneously so this is for masses of the meat of the kidney so kidney cancers distinguished from other types of kidney tumors like tumors of the line of the kidney so in tumors of the meat of the kidney we've done these biopsies with a needle through the back or through the side guided by something like ultrasound machinery yes sir so like can that then spread to other parts like secondary spread so we don't really know how kidney cancer spreads after primary treatment do we they all seem to have histologic concordance so if it's a clear cell kidney cancer in your kidney it's a clear cell kidney cancer in your lungs but that lineage issue I don't think is one though we've time for one more question I'm sorry sorry but so it's not real clear so we we use the histology of the primary to presume the histology of the other sites and when we've done things like biopsies of those other sites or we've removed them because one thing I talked about last year that I didn't talk about this year is the role of metastasectomy or surgery in the setting of metastatic kidney cancer it's always been histologically the same as the primary but that sort of molecular lineage we don't know as well thank you and I'll be back for the panel thank you very much