 Well, it's it's a pleasure to be here and to be speaking to you and I think to to the point that was brought up by Dr Abel I think it's it's truth really is wonderful to be here because a lot of our patients our families inspire us to do and to Care for and so it also gives motivation to try to move the feel for it. So thanks for being here and It is again a privilege to be speaking to you today So it what I'd like to do first and foremost is I always find it's you know cases and all of us have cases all of You are Demonstrations of the successes and some of the challenges in the management kidney cancer But to talk about a case that highlights metastasectomy and we'll talk a little bit about that And we'll sort of go and do a little bit of a deeper dive Into the various sites of disease that kidney cancer can spread to and what the resections entails and what are some of The important characteristics. So this is a patient no identifiers from a patient standpoint 60-year-old that I managed to believe about five years ago But a 11-cent arenal mass suspicious for a kidney cancer lymph nodes were slightly enlarged and concerning Two small spots in the lungs which were not very clear whether they represented metastasis and a bone metastasis in fact of an L3 So lumbar spine which had not been symptomatic up until that point But as we'll discuss was fairly advanced in terms of its potential compression and risk of fracturing Patient really was an excellent performance status and remains in that way Sorry good question. So ECOG performance status is a way we we ultimately Identify the type of performance or physical shape the patient is when we consider treatment considerations whether I'd be surgery or other Correct exactly zero means Performance that's really very fit and in excellent shape For some reason wants to go backwards okay So this is the patient's imaging studies I think we've gone through several of these this morning So you can see here the mass which is suspicious of a cancer you see some lymph nodes as well there are slightly enlarge back here and This again were the spots in the lungs They were not very large really less than a centimeter and as most of us clinically sort of say is anything less than centimeter He's really equivocal and not very clear whether it's a metastasis or not And this is the the area of the bone that you can see here quite large Again patient had not been symptomatic from a neurological standpoint, but there was significant concern in that regard And really the question is what do you offer that patient? Well, there's multiple treatments as we discussed and it was highlighted I think the care at most of our centers is multidisciplinary I think surgeons medical oncologists radiation oncologists We really bring a little bit to the table all together and I think we need to personalize the treatment of every single patient So that's what typically happens in most major centers And I think again I emphasize that has clearly been shown to offer the best outcomes ultimately for patients So really the question is would this patient be offered up for in treatment with medical therapy? We had a great talk on some of these systemic therapies Radiation or really a surgery the right way to go So really this was a case we discussed multidisciplinary and it really was felt the lung lesions were not very clear The bone area was significant concern that it could progress And in fact what we decided to do is do a combined surgical resection of the primary and the bone with Discussion with our some of our surgical oncologists in the neurosurgical program So patient underwent a cytoreductive so removal of the kidney is setting a metastatic kidney cancer So that's what we refer to a cytoreductin infractomy All right lymph node dissection removal of those lymph nodes, which I showed you and then removal of that Bony segment subsequent to which the patient had radiation to the specific areas of the bone as well Discussion point afterwards, and I know will be discussed as whether there's a role of giving medical therapy afterwards these patients So the pathology in fact showed this was kidney cancer Fairly aggressive type firm and grade grade clearly being a factor Which tells you how aggressive ultimately the cancer is the margins were clean Which is what this SM means? Lymph nodes were all positive that we were sected and the bone area clearly was a metastasis as well So what is the evidence to support this approach? Well, let's discuss that a little bit in detail. So as dr. Wood mentioned what is metastasectomy? So let's start with defining that so that is the surgical removal of cancerous growths that have spread beyond the Original tumor site to other sites of the body So as we were discussing earlier in some of the talks a meta analysis is when you basically take all the data That's out there of high quality and you really look at it in detail and say well Is there any really good conclusions? We can make whether something has a benefit So this is a study that was published several years ago From the group of the Mayo Clinic. They looked at over 2267 patients who underwent metastasectomy and really try to identify whether first of all if you completely remove it Versus incomplete remove it doesn't make a difference. Well I know intuitively that makes sense if you remove all of it. You think you would do better Well, they came to that conclusion and how much of a benefit was there? Well, fairly significant difference when you look at overall survival differences between complete versus incomplete recession You see 36.5 months versus 8.4 months So bottom line if you can completely remove it you do better So it's important again highlighting the point when you have your care make sure the people that are caring for you have Expertise know ultimately that they've done it before and also they can discuss with you with some of the morbidity Making complications associated with that recession could be So this is a what's we refer to as a forest plot Which is a very fancy statistical way of saying well when you put all the data together and these are the individual studies The bottom line is there's a favorable prognosis associated with the complete resection and that's that base that two number means essentially Two times greater. I guess Chance of cure essentially So this is another study that was published. This is a comprehensive review. It was published looking at Knowledge overall in terms of local treatments for metastasis and trying to come up with some conclusions What what conclusions they come up with? Well same thing they came to the conclusion if you can completely remove it you do better So I sort of hit that point So this is just a good summary of and it'll be sort of really the discussion points We're going to sort of have the next 20 to 25 minutes is where where does kidney cancer go to when you consider surgical resection? Well, the lungs are the most common sites so lung resections for metastasectomy is the most common And this is the overall survival associated with metastasectomy specifically for long So long the most common bone is a very common area liver as well Pancreas lymph nodes abdomen and then thyroid and head neck area and you clearly see certain areas for like for example Pancreas I really have a very favorable prognosis in terms of how patients do This is an interesting study that was published Last year and really it was done as a study in Europe It really they tried to look at sub types of kidney cancer So obviously today we know more than just histology meaning is it kidney cancer is at a clear cell or is it a non-clear cell? We actually know what kind of molecular profile meaning what kind of genes these specific tumors are expressing So this group looked specifically at the clear cell type of metastasic Neustatic kidney cancers and found there are really four different clones of cells based on their genetic profile and I mentioned this just because this is a way of looking at the genes that are being expressed and what they Ultimately are involving in terms of how cancer progresses and they in fact showed in a subsequent study that Depending on what subtype of a clear cell kidney cancer you had When you had a metastasectomy you actually did better with certain sub types So that's some of the innovative type of research and I think Information we're now getting from genetics and from molecular profiling We now know in addition to the subtype of kidney cancer based on the genetic profile How you may do with with a complete resection of a metastasis? I Would say because some some colleagues have asked that's not really being used widespread clinically But it is clearly where research is going in the future in terms of how ultimately we determine which patients should undergo surgery So this is a paper that was published from Memorial Sloan Kettering in New York of 138 patients with Metastatic kidney cancer undergoing a single site metastasectomy meaning they only had one site Which cancer had spread to and what did they find they found the patients in terms of recurrence free and cancer-specific survival actually Did fairly better than expected 84% of patients at five years had a cancer-specific survive So something more encouraging that we would typically associate with it and what were factors that associate with how patients did? Large tumors and sarcomatoid histology sarcomatoid histology is a subtype of kidney cancer Which is very aggressive in its pattern of behavior not only locally meaning in the abdomen also in its pattern of spread to other areas So those are the factors that were associated with how patients did Another question that they answered is no evidence that if you had metastasis when you were diagnosed with kidney cancer You did any worse than if you developed a metastasis afterwards and underwent this type of surgical approach So that was also an insightful type of conclusion or point that was brought up by this specific study And this is the survival curve so ultimately if you look at cancer-specific survival And I'll tell you what that ultimately means is if you look at survival specific to that cancer not meaning Not looking at whether someone had a heart attack or another cause of death You see that again patients did better than would be expected with about at five to six years 75 patients were cancer-specific. I had a were cancer-free in that regard in terms of being alive following that resection So this study specifically looked at well, you know, it's important You know that we clearly discuss prognosis in terms how you do from a cancer standpoint But an important discussion point for patients is we'll talk to me a little bit about the morbidity meaning what kind of side effects Am I going to have from this treatment that have lies not only to surgery but medical therapy You want to know what you're sort of looking into what you can expect in terms of how likely you're going to recover from an operation So this study looked at a national database of kidney cancer patients looked at over a period of about 10 years and Found in the 1,100 patients that were looked at major Complications were were found in about 25 to 27 percent of patients And it found in fact certain sites of resections did worse in terms of rates of complications like liver resections For example, we're one of the areas where you had a two and a half times higher risk of having a complication So these are also very important discussion points when you're discussing it as a clinician or as a clinical care team with patients In terms of what you can expect with the treatment What were the most common complications things like transfusions respiratory complications those are really the most common ones things like wound infections things like Like cardiac were really fairly low about a 5% incidence of having those things And that's also an important discussion point is today when we care for patients And I'm sure many who had surgery Patients are really very carefully scrutinized and evaluated by medical teams and cardiologists to really make sure you're in the best of shape When you're having an operation particularly if you have some medical condition So let's now talk about the individual sites of metastasis and how patients do with resection So lung metastasectomy, and I'm going from a chronological from the highest frequency of of sites of metastasis and resection to the lowest So again lung being the most frequent site that cancer can go to and where patients have had experience in terms of metastasectomy What do we know and I highlight this is just this is a spot of metastasis or highly suspected It would in fact was biopsy proven to represent that So this is a paper that was published from the group in China They looked at a good looking at prognosis prognostic factors of patients with metastatic kidney cancer who had lung metastasectomy So again, we'd like to talk about Survival rates again, and I think it was a good point that was brought up by an earlier speaker is It's you have to be very careful when you say there's a one-year three-year five-year overall survival Those are numbers they don't necessarily mean how you're going to do any time a patient asks me that I sort of take A step back and say look I don't necessarily can tell you what you're you're going to likely be in One two three five or ten years. I can give you numbers, but those are numbers It doesn't say those curves are you know They span a certain thing and they don't really represent everybody in this room or potentially who has kidney cancer So you have to spend a little time and really be significantly Educated as well as clinicians have to have to really discuss that in a little bit of detail So what were the factors that were associated with patients that did worse with a lung metastasectomy? Well, if your lymph nodes were involved you did worse if you had incomplete recession like we're discussing earlier You did worse if you had multiple sites of spread within the lungs. You clearly had a less favorable prognosis And so those are important factors for your clinician and for patients who have Lung metastasis or considering this to sort of be aware of and Again, this is a little somewhat busy slide But again, it really is to heighten again the fat various factors that are associated with how patients do and again To emphasize the point that you really need to take these individual prognostic factors or factors that predict how patients are going to do into account This is another study that was published This is a study from Japan and it looked at Interestingly enough surgical resection of pulmonary metastasis in a cohort of about 85 patients And what they found is the five-year overall survival rate for the group of patients was about 59 percent and complete resection again was achieved in 93 percent of patients So surgeons did a pretty good job ensuring they had resected most of the disease and the factors that predicted again How patients did were the size of the tumor the histology meaning if it was a clear cell patients in fact did better and having a complete resection And again, this highlights the point that clear cell timidly in this group of patients was a very favorable Prognostic factor versus other types of histologies of a kidney cancer This is a study that was published from Germany actually it was somewhat I wouldn't say this is streamlined treatment to lung metastasectomy They in fact not only resected it but they use laser technology to ablate the area resection So when they did the resection they use a laser technique to resect it and they were in fact very aggressive They didn't only resect patients with single-sided disease But potentially some patients who had several sites of metastasis in the lungs and I would take pause and say that is not standard approach But they sort of did this in Germany and it sort of gives a little bit of insight of how patients did. What did they find? They found that patients had a complete resection again did better and it was achieved in about 88 percent of patients even if they had several lung metastasis in the lungs and In fact the factors that predicted how patients did were a complete resection and number of sites of metastasis in the lungs So I would tell you clinically I Take a little caution when I look at data like this because if you have multiple sites of metastasis Particularly if it's in both lungs or you have other sites of disease Those are likely patients that you know it would be discussed as a multidisciplinary type approach But probably would get some form of medical therapy first before you went on to do surgery and Again, this was to show that if you had one site of disease you did better But you see in this study they did up to 20 resections in some of these patients Which again, I wouldn't say that would be a standard approach that most of us would sort of advocate for Let's go on to bone metastasis This is the picture I showed you earlier again with a fairly large bulky metastasis Which is at high risk of compression or or or causing some neurological deficits in patients So this is a paper that's a couple of years old But it was published from the group from Boston Orthopedics department in terms of doing bone metastasectomies and they found in fact in the 183 patients Which is a large group of patients that were treated 48 percent of patients under one metastasectomy and then 30 percent of patients under one some sort of Kurtage meaning excision of the inside of the of the lesion and essentially the other 22 percent of patients didn't in fact have a Resection they under want to stabilization So an area was felt to be at high risk of a fracture and the orthopedic surgeons just stabilized it And really the point of this is is there a difference between resecting it versus stabilizing it? So they looked at this and in fact found that if you had a resection of the bone metastasis You did better versus if you had any of these other two different types of approaches Again, this is sort of shown in these Survival curves where again if you have a complete resection with negative margins You clearly do better But really if whether it was a interletal cartage versus a stabilization really was no difference So it's a really either you get a resection complete resection versus other and so those are important discussion points And this is another thing whether they achieve negative margins, which was confirmed with pathology. You clearly did better as well This is a paper that was published as a collaboration Looking at bone metastasectomy treated in two places in Germany and in China They treated 114 patients the overall survival was about 9.6 months So clearly you're seeing that bone metastasectomy for example is not as favorable as we were discussing earlier with lung metastasectomy The factors that were associated with survival on multivirid analysis were whether patients had received some sort of medical therapy at some point Either before or after surgery Whether patients had a resection whether patients were put on some forms of what I call bisphosphonate therapies Which are a way of really boosting and making sure you give Reduce the risk of bone fractures by increasing bone health and favorable predictors of overall survival were those factors in fact and the resection of bone metastasis in combination with medical therapy In fact was shown to have a dramatic improvement in survival with that 31 Close to 32 months survived versus eight months People and you know and we spent some time discussing whenever you look at clinical studies, and I think that's an important point I definitely spend time and I'm sure my colleagues do the same as You have to be very careful when you sort of come to conclusions say well if I have surgeon to get treatment I do better than that if I had treatment alone Well, there's also a certain degree of selection that happens there meaning we're going to get more aggressive therapy Well, it's patients typically like we're discussing about performance status who are very fit patients who are very you know are seeking a very aggressive approach for example and Also patients potentially who are being treated at centers where they have the ability to give multi-disciplinary care So there's any time you see a study there may be some factors which may be influencing the data as well So just always take that into account whenever you look at some clinical studies and Again when you look at that patients who have bone metastasis which you see in the blue curve did better with whether they had Single sites so bone metastasis only versus if they had multiple sites of disease versus if they are in fact had the bone Metastasis left in place and again if combination therapy meaning if you had medical therapy plus resection They also did better How about hepatic and pancreatic metastasis ectomy? So this is again a CT scan showing the kidneys left in place here the patient in fact had The right kidney removed previously and you see this area right here Which in fact is a pancreas metastasis that the patient developed So what's the data in terms of these area of of metastasis and having surgical resection? So this is a 12-year follow-up study so patients were followed over a 12-year period who have liver metastasis And this is a paper that was published From the Mayo Clinic and over a period of about 11 years the median number of liver metastasis were two And the median fall up of the patients was about 26 months So a little bit more than two years and they found that most of the patients had in fact received some form of systemic treatment So medical therapy in addition to surgery alone And they found that overall the five-year survival rate was actually about 60% and there were patients that survived at 142 months was the median survival Factors which are associated with not benefiting from surgery again a higher grade more aggressive histology of the cancer and Having other sites of metastasis at that time And this is sort of putting the data together the survival rates again You see there is whenever you look at clinical studies there can be a quite Significant variation in terms of what a reported Survival rates and how patients are doing so that's also very important when you look at that or you have a discussion with your clinician To understand there is variability and experiences and how patients do and this is a paper specifically looking at isolated pancreatic metastasis if you may remember one of the first slides I showed was pancreatic metastasis in itself or somewhat favorable location for it for Metastasis of kidney cancer in terms of either medical therapy or surgical resection So this is a study of a 276 patients 28 percent of patients were treated with not only either surgery or radiotherapy So either form of a local treatment and 256 patients received some form of systemic therapy again in addition to this type of local treatment The median survival the patients had was about 58 percent at five years and Factors that were associated with overall survival was whether they patients in fact had some form of local treatment on Multi-variant analysis so multi-variant analysis is you all are probably aware is when you take all the factors together And you're sort of controlling for potential things of which may be skewing the data. What are their all bottom line? What are the factors are really impacting how patients do? So whether you had previous kidney removal of the memorial Sloan Kettering and IMDC prognostic Factors, which is just basically ways that we've developed to understand how patients are going to do based on certain characteristics either of their tumor or using blood tests to sort of know a little bit more about their cancer and And whether patients in fact had local treatments either again in the form of radiation or in the form of surgery and Again bottom line that was shown in this study Local therapy makes a difference when you have metastasis the pancreas and you clearly see that these two curves are clearly very different So this is a topic that my colleague a dr. Karam will be discussing in the next few minutes But so I sort of will sort of skim through this fairly quickly But what happens when when the cancer goes locally meaning in the abdomen either to lymph nodes? As seen here, and how do patients ultimately do does it make sense ultimately to go after it surgically for example? so this is a paper that was pleased to collaborate with my friends in Texas and We looked at this and really found that the most common site of metastasis of the lymph nodes specifically in terms of what in the abdomen has the cancer spread to are the Interadural cable region which means between the vena cava in the order and I'll sort of going back there that basically means in this specific area between these these blood vessels and At a follow-up Really of close to I believe it was two years It was found that about 52 percent of patients develop a subsequent recurrence So about half of patients will recur once again after that that initial resection and the time to recurrence was close to 10 months on Multivariant analysis like we're discussing earlier the factors which were predictive of how patients did ultimately Was whether or not you had a short time from when you develop the recurrence So typically if you have a recurrent a short interval between when the recurrence happens that that is usually a worse Prognostic factor which you need to take into account. So if it comes back early less favorable in terms of how patients could do and that was in fact the factor that was most predictive of progression and What we're able to do is really pinpoint a little bit more Where were these typical lymph nodes in terms of where the cancer had spread to and this is for a left-sided tumors? So if you had a kidney cancer in your left kidney or right-sided tumors So in this kidney where the spread the kidney cancer was spread to and those are helpful for clinicians to sort of be aware of because When you're discussing going in there removing lymph nodes if you know there's a higher risk that other lymph nodes could be involved They may sort of affect how you do the surgery or what lymph nodes ultimately you'd be removing So this is a paper Again from the from our colleagues at at md. Anderson by dr. Wood and karam They looked at 100 patients 102 patients treated over a period of about 15 years And they found that uh metastasis progression was observed in about again slightly more than half of the patients And on multivariate analysis again taking other factors the nodal status meaning if the lymph nodes were involved And the diameter of the lymph nodes were the factors that predicted how patients ultimately did And these are some of these survival curves again highlighting whether uh, you had a recurrence that happened early You did worse whether the lymph nodes were positive Atomic surgery you did worse and also this is an important curve, which apologize. I know it's a little small The site where the cancer recurred meaning if it was lymph nodes You see that patients did slightly worse than for example if the cancer had to come back in the adrenal gland The adrenal done being as was discussed earlier is that little gland that sits right on top of the kidney So adrenal is a is a more favorable location for these cancer to spread to How about brain metastasis, you know when when when this cancer spreads to the brain people say well Is there nothing that could potentially be done? Well, that's not the case Clearly there are treatments that are available and we'll discuss those uh right now So this is a paper that was published from the group from uh, memorial Sloan Kettering And they looked at doing brain metastasectomy and 50 patients treated over a 20-year period So you see the clearly that's a very large period of time very selected patient of population Some patients with brain metastasis typically today would be treated with radiation for example versus surgery The primary was dissected in most of these patients And the median survival of patients was about 31 months Mortality following surgery was found and happened in about 10 percent So clearly something very important for for patients families and and clinicians to discuss is In this series, which was again several years ago. This was published close to 20 years ago There's about a 10 mortality risk associated with the operation itself And uh following surgery uh close to half the patients in fact receive radiation treatment And the reported one two three and five year overall survival and again understanding that these are Very general type numbers are such that about five years overall survival is about 8.5 percent Favourable predictors were whether the site of metastasis, you say what on earth is supertentorial metastasis means If this was in the higher brain patients typically did worse Patients who had left-sided versus right-sided tumors did worse not really sure how to explain that other than to say Maybe that was just also maybe some statistical type reasons why that was But also if you had symptoms neurological symptoms before surgery you typically did worse as well How about the head and neck? So I've had patients over the years who for example had developed a thyroid metastasis of kidney cancer And actually when you look at it that is probably one of the more straightforward sites of surgical resection for our colleagues in the head Neck service to sort of operate on And patients in fact interestingly enough Concurrents meaning presence of thyroid and pancreas metastasis was present about a quarter of patients With thyroid adrenal concurrent metastasis and about 13 percent of patients the five year overall survival rate was about 46 percent And about 28 percent of patients develop a subsequent local recurrence in lymph nodes or other in the general head neck area Again on on looking at all factors. What predicts how patients do well aid was a factor patients who had involvement of adjacent cervical lymph nodes for example did typically worse And predictors of how patients or which patients are most likely to recur was Invasion of these lymph nodes or how long ago the patient had the thyroid ectomy So short interval typically did worse versus if you had a long interval for example So I we were discussing a little bit earlier. Well, is there a role to give medical therapy before you do these types of surgeries? Well, that's a very good question Our counterparts again in texas at md. Anderson have looked at this in a retrospective fashion So looking at their data of patients they had treated and they found in 22 patients treated across three centers md. Anderson dina farber and the clement clinic Metastasectomy was found In the retroperitone meaning in the abdomen in the lungs so multiple areas of sites of cancer And about 50 patients had a recurrence at a fall of close to Three and a half years and the median fall up of about 109 weeks 21 patients were alive and one was deceased from kidney cancer So these are you see in these retrospective studies typically patients get a host of different type of medical therapy either before or afterwards And this is another paper that looked at this This is a paper that was published in a european journal and they looked at patients I got medical therapy before surgery again Same type of question and the problem proceeding with with surgery after you got medical therapy was quite good So sometimes patients ask well if I get medical therapy might burning my bridges that I may not have surgery afterwards Well, this study would tell you not most of these patients in fact were able to have surgery The median survival of these patients when the edge of therapy was about 67 months And the probably to achieve a complete local therapy and discontinued targeted therapy was about 73 percent of patients So what does that mean? So probability that you get resected and you're off the treatments afterwards So fairly good chance that you're going to be able to sort of get off the therapies in this in this experience right here This is a fancy way of showing data where patients like out medical therapy You want to bottom line the the masses sort of shrink Well, most of them in fact did when you look at percentage of shrinkage that you see here And that's sort of what's representing you clearly see one here in which in fact grew during medical therapy And that's what as a clinician as a patient you need to watch out for is clearly if the medical treatment's not doing it You need to recess whether you need to change treatments or maybe you need to consider surgery at that point in time How about giving adjuvant meaning giving treatment after you do the metastasectomy? Well, there definitely is this is an active area of research and I think there's a lot of interest like dr Haas has mentioned earlier. I think the combinations particularly patients who are at risk Of recurring is something which we actively are looking at and I think clinical trials is definitely going to be the way of looking at this So this is a paper that was published from south korea of 33 patients Who were treated following a complete resection and got some form of target therapy and again Same thing as we were discussing before if you had an incomplete resection, you did worse And again bottom line is it makes a difference if you're going to have surgery It's important that your surgeon yourself have a clear discussion of the goals of treatment The likelihood of a resection being complete and sort of be able to sort of know and understand that The factors that predict how patients did were again complete resection whether they got medical therapy This imdc risk group which again is a way we look at cancer having more aggressive histology and having multiple sites of disease And this is shown here again Complete resection sort of makes a dramatic difference there. So this is one of my last studies I'm going to sort of discuss with is this a study that was published looking at target therapy So again medical treatments falling complete resection only 19 patients had immediate post-operative treatment And immediate post-operative treatment was associated with a better survival But again, you need to be very careful. These are retrospective studies selected patients So it sort of guides us about potential of combination treatments, but it's not a definitive meaning It's you can't make over conclusion that this clearly is the way that we need to treat patients or Or that these are the right treatments that we need to be giving patients And again, this is sort of to show you here if you didn't have a complete removal If you had a complete removal and to get treatment, you clearly see the relapse rate was much much higher versus If you had a complete removal and got medical therapy, you clearly see the relapse rate was 20 versus about 80 So in conclusions, the most common sites of metastasis of kidney cancer as we sort of went in a chronological order are the lungs, the bone, liver, pancreas The retroperiod in the brain and the head and neck Complete surgical resection is really the primitive The essential component of how you're treated if you're going to have this type of treatment And I definitely think some of these knee adjuvant and adjuvant trials are very promising Particularly these adjuvant trials following metastasectomy and there's two that were mentioned earlier Keynote five six four emotion zero one zero May help us under understand the combinations of whether checkpoint these immune modulators may be of the important in these treatments And I think this is a a slide I like to always include because there's many factors when you're considering treatment and in particular aggressive surgery patient factors disease factors likelihood of complications with surgery and then site specific meaning Lung bone and brain like we're discussing clearly know how patients are and there's a difference in prognosis depending on those sites Lastly, this is a nice summer slide in terms of the treatments and different types based on the location and just a brief just Mention of I think a mentor from any of us dr. Swanson who's part of the kca for many years And dedicate a lot of his career to the to the really focusing on metastasectomy and the treatment of kidney cancer And I just want to Definitely know that his his legacy is one that we definitely all sort of are striving for To try to make an impact on the treatment of kidney cancer particular aggressive kidney cancer So thank you very much for your time