that exists the global data on on therapy for the disease and we do this to try to get the optimal efficacy we want to choose the right drug for the right patient that's going to give us the best outcome and so there's a bunch of factors here which we've actually spent time in the pharmaceutical companies obviously they spend time maybe sometimes for different reasons they want to know why we choose what we choose and why patients choose what they choose when it comes to these different therapies and you can see listed here are the different patient factors that go into it and the different agent factors that go into it but without a doubt when we survey both doctors and we survey patients and people respond you know when when people respond truthfully the biggest factor that guides both the patient and the doctor and their choice of therapy when they're familiar with the data is efficacy so patients want this is to start off as initial therapy their first line of therapy they want the drug that works the best okay they're not as concerned about the side effects if they have a drug that works better and and shrinks the tumor more so that is something important for us to know as we're selecting these agents another field of research is trying to find are there ways that we can predict before we give the agent to a patient who is going to respond to the agent wouldn't that be great wouldn't it be great to be able to take your tumor Dr. Wood or Dr. Karam cuts out of you to send it for genetic analysis and then we find out we get a print off report Dr. Taneer gets a print off and says this person is going to get pysopinobotrant and they're going to have an 85 likelihood of response or a 90 percent likelihood of response wouldn't that be great you could hand that to your patient that's the future I think everyone in this room knows that we are doing genetic analyses now of tumors and it's not going to be much longer you know I'm hopeful that in my lifetime for sure that I would be able to see be able to do that and that's the hope for cancer is to individualize therapy to that degree so you know I've told you started off that we have seven of these drugs and we have to commend pharmaceutical companies for doing something that's tough for them to do and that is to risk it all where they actually take on another drug and so that's what happened in the compares trial that Dr. Taneer mentioned to you there was the two most commonly used drugs globally are synidinib and pysopinib and we have a trial which can be faulted now we and our academic lectures you know in our meetings we we kind of ripped the trials apart and and they're not there's no perfect trial but this was a trial that was designed to show that pysopinib was as good as not worse than synidinib wasn't designed to show that it was better it was just to show that it was similar or equivalent to and that was this particular trial what you see here is overlapping curves I mean it doesn't take a scientist to know that these drugs are pretty similar in their activity so that allows us Dr. Taneer and myself to say either drug is probably going to be okay for you either drug is going to give you the same likelihood of response but what Dr. Taneer said is that these drugs are a little different even though they hit the same targets they they they do so in different ways and with that comes different side effects and there are certain side effects the ones that are in the teal color up here that are favoring synidinib and there are a group of side effects that favor pysopinib and as you can see as I started off every patient's different you could imagine there may be patients that are going to do better with one drug over the other based upon these type of side effects and so this is what we as doctors utilize when we're choosing agents another kind of this is the when I was mentioning that I wanted to talk about novel trial designs this is it this is the first time I'm aware in cancer where we've done a patient preference study now again academically in behind closed doors scientists will argue about the validity of these trials but certainly it was from a patient's perspective this was a home run because it was an it would allow patients to have a voice to do a trial where a patient could actually vote in the as part of the trial results whether they liked one drug or another based upon side effects and that's important to know when we have drugs that are very similar in their activity if drug works about the same it's important to know which which one's better for the patient intolerance and so as Dr. Tanier mentioned I won't go through the details of the trial they looked at both the doctor's impression of benefit and they and side effects and they looked at the patients and we were able to show that actually the average person seems to favor pysopinib in regards to side effects better than synidinib so that important stuff to know and there was the breakdown that Dr. Tanier mentioned to you 70% preferring pysopinib 22% synidinib again with a lot of scrutiny on this trial this was not a perfect trial but at least it gives you an idea that there are differences between the drugs that's first line you know um what about second line well we recognize we're not curing anyone despite these unique cases and I have them in my own practice I have patients on frontline therapy synidinib and pysopinib for seven eight nine ten years I mean amazing lengths of time but that's not the average person we see the average person is going to have progression on one of these therapies at some point and then the decision is to move on to the next therapy and our goal as doctors is to give our patients all of as many options as many of the available agents as possible to hopefully get an additive benefit of prolonging survival as long as possible and what we are trying to figure out is what's outlined here contribution is each of these different therapies we give patients we're trying to understand how much each of those therapies add to the overall survival but our goal is the same give as many of the therapies as possible to our patients and I will tell my patients when I first meet them that that is our goal so that they understand that it's unrealistic to think that synidinib or pysopinib is going to be the only drug for them that's what we start off with and that we have all these other drugs that we are going to sequentially use to drive survival as long as possible and we've got all these drugs again to do this and two of the ones that have been most most punitively most commonly used as next drugs outside of a clinical trial with a caveat doctor you know md anerson baylor rymat we are big clinical trial centers so our patients are going on trials but for the average patient who's not on a clinical trial they're going to be getting one of these drugs next and whichever one they don't get next they get that one after so we sequentially use these drugs and the two most commonly globally used drugs now as second-line therapies are either the affinitor everolimus mTOR inhibitor or exidnib which as dr. tenir mentioned was the second generation powerful vegev inhibitor and so at the end of the day this is my this is finishes my review of what you've heard so far is our goal is we want to achieve long-term survival in that we recognize in 2014 is going to require careful selection of agents for each individual patient and i can tell you i can speak in general terms this is generally what i do first second third fourth line but that's a generality and it changes based upon individual patients it changes upon the individual patients response to the therapies so the way they respond to the first line therapy may influence my choice of therapy in the second line setting the side effects you can imagine when they have a side effect in the first line therapy that may influence my choice in the second line therapy etc so we do even though we make general statements about what how we're going to use the therapies we do want to tailor that to individual patients okay busy isn't this a nasty slide right tough slide um i borrowed some of my slides from tony terry who's one of our colleagues at harvard um so if he's watching on the on the videocast he'll recognize some of these slides um this slide very busy cartoon is depicting the sites of action um biochemically in the cancer uh cell in the microenvironment so we've got up here synidinib, seraphinib, posopenib, and exidinib which are predominantly working at the endothelial cell that's the cell that makes the vasculature and then we've got the mTOR inhibitors which are going to be working down here in the mTOR pathway well we recognize cancers are so complex i mean major complex phd level complex that there are a variety of other targets to potentially to hit to potentially affect kidney cancer growth and one of them that's been looked at here is in this red blocks is growth factor receptor for MET you hear about MET which is a growth factor receptor in FGFR fibroblast growth factor receptor those are two targets that novel drugs for kidney cancer have been studying and the first one to talk about is cabosantinib cabosantinib is a MET inhibitor it also inhibits VEGF and this drug cabosantinib has a brand name of Cometric and has received FDA approval for thyroid cancer already but our colleague Tony Twerly who's trained with me at Cleveland Clinic and is now heading the kidney cancer program at Dana-Farber and Harvard I did a trial and patients with refractory kidney cancer and including patients with a subtype of kidney cancer which doesn't do well with therapy a psychomatoid type of clear cell kidney cancer and he was able to show in a refractory setting so third fourth fifth line setting that there were good responses confirm partial responses of 28% on patients there was only 25 mind you in this smaller trial 52% of patients having stable disease in a median progression free that's the length of time the patients able to be on the therapy with control of over a year so an exciting drug and they included in this trial some different correlative studies and this was radiographic responses using volumetric scanning and just to show you this was the baseline of one of his patients on the trial and then after eight weeks of therapy showing dramatic response and this is in point because this particular patient you can see was a heavily pre-treated patient patient who's already had four lines of therapy they had synidinib they had a traditional chemotherapy drug called gem cytobine which is a chemo drug which is used in kidney cancer they had the mTOR inhibitor affinitor which is commonly used second or third line and they had this drug utenine might not recognize this ramyut serumab ramyut serumab I don't even know if I pronounce it right but it's it's an abastin or bevacizumab like drug it it targets VEGF receptor 2 antibody so this patient's been treated with drugs that should work in kidney cancer and they're getting this as a fifth line therapy showing this degree of response so obviously a lot of excitement was generated by this trial and so this has resulted in cabozantinib being studied in two major phase three trials and if these trials are positive the drug will move to FDA for regulatory approval these trials are ongoing as we speak in the cooperative group the alliance clgb cooperative group don't tell me why they come up with these names but that's a group of cancer centers generally through the midwest of the united states is doing a randomized phase two trial comparing the cabozantinib drug with upfront synidinib at the traditional schedule four weeks on two weeks off so this is going to be in a front line setting and then probably the big trial that will result in regulatory approval though is in the second line setting and that is the meteor trial and nizor are you doing this trial here yes there you guys have this available to you in houston i'm also doing it in dallas this is a major phase three trial this is the regulatory approval trial for cabozantinib versus everolimus and patients have had to have had progression after frontline vedgef targeted therapy the primary endpoint is progression free survival and secondary endpoints overall survival okay so that's exciting there as you've heard already there are different types of kidney cancer right so clear cell is the predominant type the one that we know the most about the second most common type is the papillary type and the papillary actually to be more sophisticated and more complicated there's actually two types there's a type one and a type two the type one hereditary papillary renal cell cancer is associated with a met abnormality met gene so just like vhl was a gene associated with clear cell met is a gene associated with papillary renal cell cancers and we have developed inhibitors that inhibit met so and met is involved in other cancer types too but in kidney cancers what we're interested in there was a drug ferretinib which is a dual inhibits vedgef receptor and inhibits met receptor was studied by our friend tony again in patients with papillary renal cell cancer showing significant evidence of benefit this is what we call a waterfall graft and so what's going down negative here is the amount of tumor shrinkage that's seen so you can see the majority of patients are having some degree of tumor shrinkage when they get this drug in their papillary renal cell cancer and it's a minority amount that actually has tumor growth and they showed a progression free survival of almost 10 months which is not bad in comparison to other drugs that we use for the disease so again an exciting new drug for pigeonhole for a rarer type of tumor papillary um what about biomarkers we talked that we don't have any predictor markers in the future there with maybe um genomic sequencing and and looking at the tumor but we're also looking at biomarkers we're looking at ways and chemicals that we can test that we could determine whether or not a patient's responding to a therapy in how long they'll respond and there's a variety that we've looked at unfortunately none of them have been validated yet but we continue to search for these these include things for interleukin 2 hyacinthus interleukin 2 trying to find ways we can predict and um who's going to benefit from that vedgef targeted therapy there's a list and mTOR inhibitors so this list and is continues to grow and is ongoing as i end now you know we've talked about i think cabozantinib which is probably uh most would agree is one of the major drugs that's on the horizon it's it's an oral drug um similar to that to sutent votrient family in regards to it being an oral drug with similar side effects but inhibits um cmet the ferretinib drug is is for a rarer indication the next big group that is really on the horizon is the immunotherapy you've heard about in detail so just briefly there's a couple vaccines that are being studied vaccines that are being studied in patients and the refractory setting in a vaccine types of therapies that are being studied in patients um as adjuvant therapy um and this is just a phase two study looking at one um this ima-901 which is has 10 tumor associated peptides and these tumor associated peptides are supposed to stimulate the immune system to fight the cancer and they were able to show and patients that actually develop immune responses to this peptide a significant benefit and and these were patients with advanced rcc who had prior therapy with both interferon interleukin 2 tkis which would be like the synidinib bisopenib and had documented progression that when they gave them this type of therapy and the patients had an immune response to it that they were able to have benefit um this has resulted in a phase three trial that i have not seen the results of yet um looking at this in combination with suthent so people say why would you take an immune stimulator and combine it with suthent well part of the story that you haven't heard about is that suthent itself besides inhibiting vegev and blocking blood vessel development is an immune modulator itself you know we haven't spent a lot we don't fully understand it well but it is clear in labs around the world that suthent can affect the way the body's immune system is responds to the cancer and so there's been a lot of immunologists that have worked on this um one of my mentors at the Cleveland Clinic um has um published on this and so the thought is that maybe you could use this stimulator of the immune system this pen 10 peptide vaccine if you will and combine it with suthent and hopefully um adjust the t-rex and the the tumor and make them more responsive there's another trial this is a um a autologous dendritic cell vaccine i don't know if you're doing this nizer i'm not you are so this is the adapt study that is a similar type of thing where you're combining um the the therapy sequencing it with suthent again for a lot for the same reasons that suthent does have immune modulatory effects on the immune cells the tumor associated immune cells and then finally as i and you've heard this eloquently mentioned already that the break on the immune system is this interaction between pd1 and pdl1 and you you know there's energy which is when you immune system is you know you're allergic you don't have reactions to normal immune stimuli or you on the other extreme you have autoimmunity and i'm sure you've heard of immune related diseases like rheumatoid arthritis sle stuff so there can be situations when your immune system just attacks everything so you know the problem with the pd1 pdl1 is that's the break and so we're trying to design therapies that will take off the break that the cancer puts on the immune system to take it off so that the immune system can work but at the same point not throw someone into autoimmunity where they're having the immune system attack the body because that produces bad side effects that would be similar what happens in bone marrow transplant patients and so there's been a lot of work into this their pd1 inhibitors and the pdl1 inhibitors these are them shown here on the slide from earlier studies this again is from my friend tony's presentation at 2013 asco meeting you can see with the nivola map which is the bms compound that there's this is a spider graft and again anything going down negative here is a response it's the degree of tumor shrinkage you can see the majority of patients that got this pd1 inhibitor this this checkpoint inhibitor they were having benefit with tumor shrinkage with kidney cancer and then you can see one of the pdl1s also about 50 of them having some response to the therapy so both of these antibodies to those checkpoints that are the breaks of the immune system are demonstrating benefit one of the interesting things is that we can actually test the tumor for expression of pd1 pdl1 and so when they look at pdl1 the problem is it's not perfect it's like PSA testing it's not perfect so it's unclear whether this will be useful for us but but clearly if a tumor is expressing pdl1 those are the people that are getting their responses to a pdl1 inhibitor versus if you don't express the pdl1 you're not so you remember what i initially said when i started the talk the future would be able to do a test like this on someone's tumor and determine who is going to benefit from the therapy and who is not before you give the patient all the side effects of the therapy and so this is a step in the right direction again but it's not perfect it's unclear whether this will move forward and then there are there's several phase two trials of nivolumab this is an ongoing trial phase three trial it's on the verge of closing soon it closed already i thought it closed in decemberish time period december january but the results will be forthcoming within the next calendar year most likely of nivolumab versus everolimus as a second line therapy or third line therapy so patients could have had one or two prior vegeth therapies and get this as a second or third line so whenever you see phase three trials like this will you have the the experimental drug comparing it to one of the standard drugs that should tell you that that is a registrational pathway and if they beat it if they win they potentially can get the drug approved so that's what the nivolumab the pd1 inhibitor the pdl1 inhibitor which is the roast product we actually have um open i don't know if you all do but it's a front line trial and it combines the pdl1 with bevacizumab that's one arm versus sutent the other arm as a front line therapy and it's a phase three trial of that particular agent that that trials ongoing so you can see so summarize we've got cabozantinib which is uh phase three trials ongoing which is you know a very exciting drug that has high hopes that will become approved and on the market then you got these two agents the nivolumab phase three trial already completed waiting results and you got the upfront which i can't pronounce the name of that particular drug it's the roast pdl1 antibody which is ongoing so again three new drugs which have real hopes in the next year or two to hit the market so as i end i think i'm up with time chris is standing there thank you thank patients thank the kca thanks for your attention to wrap up the didactic portion of this none of this would be possible without the support of the kidney cancer association and i often find that patients are not aware of this incredibly valuable resource so we've invited kary kanoski to come and tell us a little bit more about what the kidney cancer association does kary hi so my name is kary kanoski and i'm the vice president of development and public affairs for the kidney cancer association and as dr wood mentioned um that you know sometimes as we're organizing these meetings we forget that a lot of you are new you know newly diagnosed and don't know a lot about what our organization does and how we might be able to help you so first the association we are an international not-for-profit organization and we have patients family members friends physicians nurses and other healthcare professionals that are part of our organization the mission of the association even though it's kind of long up there is pretty simple is to eradicate this disease be that the pain and suffering that the patients and their families both experience through this diagnosis the mission is focused into three areas education research and advocacy and i'll just talk a little bit about each of those specific areas but first for those of you that might not know much about the association as we were founded in 1990 by Eugene Schoenfeld um Eugene was a professor at the medial school of journalism at northwestern and was diagnosed with kidney cancer and at the time in 1990 there were no meetings like this there wasn't really much of an internet there wasn't really anything that gene could do to learn more about his disease there were no treatments and so he you know this wasn't acceptable to him he didn't want to just be diagnosed and go home and leave it at that and give up so he talked to his doctor and his doctor challenged him to do something about it so gene stopped stopped working and his wife you know was willing to support him and this organization and get it started and he took a few other patients and a couple physicians sat around his kitchen table and said what can we do so gene had message boards online before you know people were really utilizing those and he took a few people around the kitchen table to an organization today that serves over 100,000 patients and families and more than 102 countries and I think he'd be pretty amazed to see as we mentioned this morning that we're here at about our eighth or ninth meeting for patients and families here at MD Anderson in terms of education we provide support for both patients and for physicians so in addition to meetings such as this that are about you know a day to a half day meeting we do small support group meetings throughout the U.S. so if they're you know check on our website we've got an events page that will let you know if there's a meeting in your region and if there's not there's an email link that will take you to someone from our office that can help you get something started in your area so it can be something as simple as monthly every couple of months for for patients and their families to get together and you can have a speaker or just talk about you know kind of things that you're struggling with or you know positive things that are going on that treatments that might be working we also have webinars and videos available from the website and if you go to kidneycancer.org usually right in the front and center they'll be the newest video that will take you to our youtube page where you'll see a listing of videos from meetings like this we have one-on-one interviews with different physicians talking about trials that they might be working on and each of the members of our nurse advisory board has also done a short video to talk about the different therapies and side effects that you might experience for physicians we hold two large symposia each year one in the united states in the fall and then one in a different european city every spring so in a few weeks we'll be going to Dublin where we expect about seven to eight hundred doctors from all over the world to come and talk about you know some of the therapies the trials that you learned about today and some things that are still in early phases and you know what we hope to see in the future as i mentioned kidneycancer.org is probably the best place to go when you have a question be it newly diagnosed you hear something new from your doctor and want to learn more about it we try to keep the site up to date on a regular basis so there's always some new news right on the front page that'll take you to articles that you might have heard about clinical trials that you might want to learn more about we've also got a can't see it on there but where it says leave a message is usually that'll pop up and it'll be a chance to do an instant chat with usually myself or bill bro or always online so if you can't find something on the website or want us to help direct you somewhere just pop your question into the chat box and we'll be able to help you with that as i mentioned we do have some resources for clinical trials i think you've learned a little bit about some of the ones that are going on now but we do have a link to the national database and a matching service provided by emerging med so these will help you you know you can put in some information about yourself what therapies you might have been on the emerging med site will have somebody that you can call and they can help help direct you to a trial that might be right for you and then we've also got educational materials just to help better explain what a clinical trial is why it's important to participate in one that's one thing that we find is a lot of patients will contact our organization and say well i keep hearing about this but i don't really know what that means and when i have all these drugs that are available why would i want to go on a clinical trial so we've got a few videos that are new now that talk to you a little bit more about that in addition our publication we have kidney cancer some of you may have had an opportunity to read this if you contact our organization you will be able to order a copy or you can download a pdf or if you have a kindle there's we have an application for we have kidney cancer and its companion piece survivor stories about two and a half years ago one of our board members who's a kidney cancer patient thought that you know we've got all this valuable educational material with we have kidney cancer but we're kind of missing the personal stories and you know there's everybody's got their own story some just having surgery and you know no metastatic disease patients who've lived for more than 20 years going from from trial to trial and therapy to therapy and so he thought it was important to share those stories so we have a few um few patient stories and then many of them have their caregiver another loved one that kind of talks about that aspect of dealing with kidney cancer so if you haven't read either of those i would encourage you to visit the website and download a copy of either and then in terms of social media which we have seen grow um i should go back and look at my videos from this meeting every year because it seems like every time i come it's 20 000 more patients signing on to facebook and it's amazing how much that's grown i think we're over about 90 000 on our main kidney cancer facebook page now but every day you can talk to patients and family members from all over the world you know people want to tell their stories many times it's someone who's newly diagnosed and is looking for you know looking for help doesn't know where to turn once to hear other people's experiences on the same for our twitter page and then our two video channels youtube and vimeo um where you can go and visit some of the videos that i mentioned earlier about clinical trials past meetings such as this and the medical symposia while they're four physicians and healthcare providers only we do record the video of those meetings so that you're able to go and see the kinds of discussions that are had at that meeting and so with that i thank you all i hope that you've enjoyed your day and learned a lot and if at any time you have any questions you know don't hesitate to contact us just one reminder to that you will be receiving a link to a survey probably today or tomorrow just to get some feedback from this meeting so that we can continue to improve every year and make sure we're providing the information that you want so thank you again my homies all right can i have the uh the my esteemed colleagues um up here for the panel esteemed in quotations dr prom would you join us dr hudson dr gound shape him look i don't want to sit in the first seat who's that from a team that's dr hudson that's dr hudson seat i want to share with you don't smack me all right so this is uh another fun part of the of this conference i you know we do these all the time professionally where we call them tumor boards we're basically difficult or challenging or interesting cases are presented and you get sort of an opinion a wide variety of opinions about what to do and i think it's helpful for patients and families to understand that you know medicine is an art not a science and you know there is many times no right answer but uh it oftentimes is helpful to listen to you know the physicians going through a process of decision making uh as they are learning the facts of a case and helps you to better understand you know sort of where our minds are at the time uh so i have a series of cases to present we'll take a little break somewhere in the middle to go out and get the lunches and come back in and then finish up the the program with some cases um we have a steam panel of medical oncology and uh urology here like to remind my colleagues that we don't need to know what we could do we want to know what you would do try to keep your answers succinct and short as are um and we'll go from there all right so here's the first case so this is a 79 year old white female who presents with right sided abdominal pain she actually had cholecystitis at the time she presented and she went on to have a laparoscopic cholecystectomy uh which is gallbladder surgery for the uninitiated and she also was noted to have an incidental right renal mass she has a past medical history significant for hypertension hyperlipidemia hepatitis B and um arthritis she's previously had the cholecystectomy as well as a hysterectomy CT of the chest is negative and her labs are all within normal limits so you can see her films here she's obviously also had back surgery she's got some instrumentation in her back so just to show the audience uh you know all this this uh shiny stuff is metal present in the ladies back and it causes artifact on CT sometimes obscuring things and she's got this mass present in her right kidney right here this is another view on just the different phase of the CT scan where they let the die circulate a bit longer and you can see she's got this mass measuring probably about three to three and a half centimeters uh in the lateral aspect of the left kidney it extends down into the central part of the kidney at least to pierce that contact with the renal sinus and the collecting system here and she has a normal uh contralateral kidney as I said her labs are all within normal limits including her renal function so Dr. Karam how would you like to manage this patient all the options and I know you don't want me to say what all the options are so if you say them briefly you can so active surveillance is an option but I wouldn't recommend it given the size of the mass being more than three ablation I would not recommend since that mass is quite deep into the kidney the main options I think here are partial nephrectomy or complete nephrectomy if the patient's healthy enough I would recommend a partial nephrectomy but radical nephrectomy is definitely not the wrong thing to do as well but if she wants radical I would biopsy her first she wants what you want Dr. Karam what do you want partial nephrectomy okay would you do it through a robotic approach or would you do it through an open approach uh robotic you would do it robotically interesting okay yes um Dr. Mateen thank you for joining us this is a uh this is a 79 year old white female who presented with abdominal pain some past she's got some comorbidities previous surgery CT negative CT the chest is negative and she's got that right sided renal mass what would be your approach in this patient uh what was her kidney function normal labs are within normal limits her GFR is probably around 75 okay I give her the option of her laparoscopic radical versus uh um we do a robotic partial the only thing I'm a little bit it's a little interesting looking is that I can't really point but there's a part of it that at least on the other films looks like it's invading in the collecting system or in a vein or is that just artifact can't tell uh it's not it's not invading into the vein although it does have it does have contact with the collecting system for sure yeah so there's you know there's trade-offs with both those procedures she's going to lose significant renal function by removal of the whole kidney the partial on the other hand would be associated with somewhat higher uh complication risk so what do you want to do doc um if she was she left it up to me I would do a partial okay and you and you would do it robotically yeah um Dr. Chapin any role for neo-adjuvant therapy here okay that's the thing how would you manage this patient I would I would offer a partial as well but I actually would do this one open I wouldn't do this robotically and she did go on to receive an open partial nephrectomy and it was a stage t1a clear cell and her post-op of course was unremarkable so any would anybody do a biopsy ahead of time only if I'm planning to do a radical nephrectomy so explain the logic of that or active surveillance just I would hate for someone to lose their kidney for a three centimeter mass that could be benign so if you're going to do a radical nephrectomy you would do a biopsy to prove for a small mass yes if I'm going to do a partial nephrectomy there's no reason to do a biopsy because I know the rest of the kidney is still going to be there and if the biopsy came back as benign you would observe or I would not go for the radical I'd change it and do a partial if that was the second option huh what if it's you know you know sometimes the biopsy doesn't always say benign benign sometimes it's inconclusive or oncocytic so you know observation or surveillance would be more of an option at that time as well but if the patient is having symptoms such as hematuria like you said this is very close to the urinary system there on the second picture on the right it might be an option to still do a partial nephrectomy I think it's an issue you know it's it's unconventional we don't think about doing partial to decide to do a radical I mean to do a biopsy when you're considering a radical but I think the logic of it actually makes sense and it may not have 10 years ago when we weren't able to distinguish benign from malignant quite as well but I I kind of buy that argument what about the argument that if it's active if we're going to do active surveillance we should do a biopsy do you agree with that I do you know I I've become I used to leave it very optional for patients it's still optional but I do encourage it I think most patients want to know if they have cancer or if they don't and it also puts them in a position of power when we're observing it and it does something that is unexpected and that's not a not infrequent so it may shrink it may get bigger but then you're in a position of more power as a patient I think when you kind of know what it is so that is an unusual perspective for a urologist most of them would not biopsy or be I don't know what would the other guys do show the hands who would biopsy for active surveillance and who would not so who would biopsy not everybody okay dr crumb what's your selection criteria so if I you know we have some patients let's say if a patient's 85 year old and has a one centimeter mass realistically whatever that biopsy is going to show we probably won't be doing anything so unless a biopsy is going to change something that I'm going to do I would not obtain a biopsy now if a patient says I will not do surveillance unless I have a biopsy it's a different story but if the patients leaving get to us to decide or to help them decide I would not do the biopsy unless it's going to change what I do meaning if I'm going to sway me from surveillance to do some form of intervention like surgery or ablation therapy but when would you use a biopsy for active surveillance that's not the same question that you're answering the patient we've already decided we're going to go on active surveillance who do you biopsy who do you not so if you've decided already you're doing surveillance why would you biopsy that's the question I'm asking right so it's in my way I'm thinking of it backwards if I'm used to decide I'd use the result of the biopsy to see if I'm going to do surveillance or not so if I'm doing surveillance what is the biopsy going to tell me if I know 100% I'm doing that you know I guess my I think that's fine the thing is things don't always go the way you expect and again I think having information puts you and the patient in a position of power so there's always unexpected outcomes whether the patient gets better or the tumor does things you don't expect it to so you know even in those for me for even for cases where we know it may not change the management at that time period I still encourage a biopsy I guess so then my esteemed urology colleagues help me as a simple medical oncologist understand because we've I've had your colleagues from Philadelphia you know say that they want to avoid biopsy and they have all this data that they've published about monitoring how much growth rate there is in a small renal mass to predict whether or not the small renal mass is malignant based on a growth rate criteria so it just doesn't make it seems counterintuitive to want to biopsy that because I think the question is different is your data sets would be different if you knew there was cancer there and you were still going to observe them then I think you're using data based upon low metastatic potential and the size versus the data that exists from Uzo et al when it's a small renal mass that you don't know and you're you're basing the data set on whether it's malignant or not so I'm just confused as to I don't know the rationale I'm not aware of data from them that talks about growth rate predicting malignancy I thought that's what the small renal mass whole debate was because with the small renal mass the reason that you're observing is because there's a certain percentage of those that are going to be benign yeah and so the growth rate per year is predicting the likelihood of malignancy and that's a different and mindset that if you knew it was cancer you would want to monitor it because if it was below a certain size it wouldn't metastasize so yeah two different well not really because as it turns out oncocytomas grow and in fact they may have a higher growth rate than small renal cell carcinoma so the growth rate actually does not predict histology although I mean alterations in growth rate may trigger an intervention so for instance you know they're normally growing at a rate of two to three millimeters per year and all of a sudden it jumps up and grows seven millimeters might say holy cow we got to do something exactly um you know my practice I typically don't buy up see patients on active surveillance I you know sort of like I already decided that I'm not going to intervene so I'm not sure I really want to know and you know if the patient asks for one I'll do it but otherwise we typically don't all right I think we beat this one to death let's move on so this is a 72 year old white male who presents with uncontrolled hypertension uh he underwent abdominal imaging which revealed an asymptomatic renal mass past medical history significant for hypertension peripheral vascular disease disease with a stent and the left lower extremity physical exams unremarkable CT chest bone scan negative hemoglobin is nine creatinine is 1.3 with a GFR of 51 so GFR just means kidney function glomerular filtration rate um Dr. Chapin these are the films give us your thoughts about this and how would you how would you manage this patient so obviously there's a left renal mass um and that first image are you showing us something different or is that is that medially is that renal vein or is that nodal tissue I'm not I'm not sure doctor yeah a single image and it looks like it's potentially renal vein involvement of course do you want to show that for the patients I will I was hoping to get Dr. Chapin a consult first Dr. Crom do you see renal vein involvement looks like it this is the renal vein right here what's happening thank you somebody's got control of my mouse it looks like this is the I know how you do okay we do so this is the mass here and this is the left renal vein you could see it going all the way to the vena cava and looks like this is some sort of a tumor or filling defect here and that's pretty much it that's all so you have a locally advanced tumor with evidence of renal vein involvement what are you going to counsel the patient are you going to treat the patient what are you going to do so I would do a metastatic workup first okay we did that that was negative so in the setting of a of a renal vein involvement in the absence of metastases I would offer him a left radical nephrectomy okay so a couple questions would you do it open or would you do a laparoscopic or would you break out the robot yeah I mean anything that's been involved involvement of renal veins I've been doing them open okay I know Dr. Mateen may have a different opinion would you do a lymph node dissection or no no dissection in the absence of clinically apparent nodes only just because you and I have different opinions on this in general I would I would not necessarily do a lymph node dissection this if at the time I felt something was clinically apparent or enlarged at the during the open operation then I would do a lymph node dissection if I were to do a lymph node dissection I would include the inner order cable nodes as well so what he's saying is that at the time of surgery if he was going to do a lymph node dissection he would take out the nodes along the aorta and also between the aorta and the vena cava Dr. Mateen how would you approach this patient yeah I think open is fine if that's what you're comfortable doing I barring any other findings I think we could do a good laparoscopic procedure here I would probably remove the nodes alongside the aorta but I wouldn't really go out of my way to to do more than that okay Dr. Koran any different thoughts I would do it open just because on the left side I feel less comfortable doing the laparoscopic when there's been no vein involvement it's much easier to do it on the right side for me at least so I would do an open on the frectomy and then do at least the lymph nodes on the aorta on the left side okay would anyone consider this patient for a neoadjuvant trial if there is one available yes okay so patient undergo surgery and it's clear cell grade three obviously t3 ACE is involving the renal vein um Dr. Chapin how would you follow this patient after surgery so clear cell grade three did you take out nodes or no took out nodes nodes were negative oh yeah so I typically get a a six-week follow-up imaging and I know that that sounds aggressive to some but um CT abdomen chest abdomen and pelvis actually at six weeks to see if anything is apparent and also the set of baseline for comparison and then I'd follow them up with imaging every at least every four months initially for the first year so you follow them every four months for the first year and then beyond that every six months for two to three years depending on how things are looking and then yearly thereafter okay Dr. Mateen how would you follow this patient yeah very similarly either every three months or four months depending on some other factors um you know you talked about the stage the grade whether there's necrosis there whether there's other concerning findings what did you do with the adrenal incidentally um what would you do with the adrenal what would you do you know I think it's one of those honestly it's uh you're damned if you do and you're damned if you don't um I that's sort of my conclusion after 12 years I've removed it in cases like this and it's not involved and then they get a metastasis in the other adrenal a couple years later you don't remove it and then they maybe develop disease in that adrenal and then you wish you would have removed it and then you know three years later so I I really I don't know when it's more locally advanced like this I feel a little bit more strongly about removing it just because it's associated with a higher chance of there being micro metastatic metastatic disease in there and for all of you out there if the adrenal looks normal on CT scan um and the cancer is not directly involving it it's supposed to have about a 95 plus percent predictive value meaning it's usually not involved but it doesn't mean there can't be microscopic disease there so right and and you know particularly I found especially on the left side where the adrenal vein drains into the renal vein uh and you have a tumor thrombus it can be quite challenging to try and spare the adrenals and spirits uh it's been a strain so I took the adrenal on this side yeah good one so so can I ask uh are there guidelines whether when you should have uh when you should do like add an electomy with the nephrectomy and when you don't have to so the I mean not formal guidelines to my knowledge but I mean basically with with modern cat scanning or modern cross-sectional imaging I should say both MRI as well as cat scan if the adrenal gland is phenotypically normal on the scan then OzR you can spare it and obviously make an interruptive assessment at the time of surgery even if it's an upper pulled kidney mass even if it's an upper pulled kidney mass because a lot of times there'll be a layer of fat between the two so in this patient who has uncontrolled hypertension it could be due to the tumor it could be due to the adrenal glands of course it could be due to other reasons as well but uh in this case would you consider uh to remove the adrenal glands or at least you know look for whether there is any adrenal glands in movement with the and controlled hypertension on the on the left side yeah yeah I mean while we took it out you know I mean they did do a feal workup so the the point is that sometimes tumors of the adrenal glands such as something called a feal chromosytoma can be a source of um hormonal release that causes high blood pressure tachycardia can actually cause a stroke and he's alluding to the fact could that possibly be at play here and the answer is possibly but there are blood tests you can get to rule that out before surgery and it's important to important thing to do before surgery because you don't want the patient to have a hypertension hypertensive crisis in the middle of surgery okay let's um let's get our medical oncologist involved so this is a 49 year old gentleman who presents with gross hematuria he has no past medical or surgical history his performance status is zero his bone scan and MRI the brain are negative he has a CT chest that demonstrates bilateral pulmonary nodules he has a locally advanced tumor involving his left kidney and he also has multiple hypervascular liver nodules so here you can see this locally advanced tumor involving the involving the left kidney here very hypervascular here's the renal vein coming across to the vena cava there does not appear to be any involvement of the renal vein you can get a hint of one of these hypervascular nodules in the liver right there that whitish blush and here's another one here another whitish blush in the liver so he's got at least a couple of areas that are you know concerning within the liver and then some minimal disease in the lung you can see there's a nodule here there's a nodule here and actually uh here there's a nodule here so small volume potential lung metastases you know they're sort of still indeterminate at this point um Dr. Tenier this patient presents to you what are you going to do biopsy biopsy the renal mass and the biopsy is going is done to tell you what what cup of renal sarcosinoma he has right and why why is that important because it might guide the therapy if it is a clear cell has a different therapeutic implications different prognosis if it is non-clear cell the same way so i think a biopsy is important before we start systemic therapy because the patient does have metastatic disease to two visceral organs multiple liver multiple lung is not good to proceed with upfront cytoreductive nephrectomy so i would advise the patient against having cytoreductive nephrectomy as an upfront strategy so i would get biopsy to confirm the diagnosis of kidney cancer and to know what type it is to guide therapy okay so in most scenarios as brian alluded to the presence of liver metastases is a contraindication to performing cytoreductive nephrectomy because in our experience patients don't do well they they they have a hard time recovering and it becomes this race between you know whether or not they can recover from the surgery to get their targeted therapy versus the disease taking over their body and most of the times especially with liver mets patients will lose that race um dr hudson what are your thoughts about this patient i generally agree with that i think that um you know i would see this is a relatively a gray zone i'm sure that there are places around the country that would offer cytorectomy upfront but it's more of a judgment call um on this the things that would lead you wanting to be aggressive would be you know the age of the patient um and the fact that the disease outside of the kidney is a small amount of the total cancer burden that the patient has so if you did the surgery and he recovered you would have effectively removed 70 percent or greater of the tumor volume in the patient um so so i think knowing the symptoms the patients having coming in the door would be useful um knowing if you could um how rapidly things were progressing um would help you in in situations where you had rapidly progressing disease where you knew patients had different imaging over the past couple months that you knew the cancer was progressing quickly that would be clear indication not to proceed with side reductive surgery so um i i i hear and understand the the concerns about the liver metastases it's it's a very this is a real life case um real life patient you know and it's a tough decision to make um i can just share and i'm sure you know that around the country you'd be getting different responses okay but we want your response well that's what i'm saying i think in this particular situation um with all things being said if you told me the patient had um was completely asymptomatic um and was and wanted to be aggressive i would lean towards side reductive surgery if the patient was having any degree of hypercalcemia or any type of poor risk factor on the traditional hang criteria um i would lean against that and would proceed forward with targeted therapy and what would that target therapy be um either a votrian or suitent dr teneer you never mentioned what therapy you'd give ideally participation in clinical trial but i think either one of these two uh are acceptable okay um dr uh karam what are your thoughts so i want to ask dr teneer would this patient be or would you not send him for consideration for surgery until you have biopsy proven liver meds or are we going to consider those tiny areas liver meds without a biopsy i know they're very small and it's hard to biopsy them but maybe they're hemangiomas maybe they're nothing so this patient might be losing an opportunity again just for the sake of discussion i think if you have a uh uh good city or an mri and these clearly uh you can tell that these are not hemangiomas but rather uh liver metastasis i don't think really necessarily there's really a need to do a liver biopsy now if you are uh not sure about liver uh metastasis or not then i think you could do a biopsy of one of those liver lesions instead of biopsy the kidney biopsy deliver and uh if then it is definitely metastatic then you have the answer but i agree i think we need to get more data about uh the other parameters that we take into consideration to uh categorize the risk of this patient in terms of this good risk intermediate risk or favorable what would those be risk you know anemia hypercalcemia as Tom mentioned serum ldh platelets white blood cell count i understand his performance as zero but i think these other laboratory they're all normal okay so he has an intermediate risk disease by virtue of presenting with advanced disease uh and uh so that's one risk factor and then he has uh didn't you say anemia wasn't here or the hemoglobin is okay hemoglobin is okay how bad is his gross inventory i mean i think that's also an important factor to consider if the the bulk of the tumor in this patient is in that kidney and looks like from the scans more than 95 percent of the tumor in this patient's body is in the kidney and the patient's having severe yeah one of the sort of grossing material is urine's clear now okay i mean that's just a factor that we should consider even though the patient might have small liver metastasis it's hard for me to buy not wanting to do surgery that can affect me for small volume liver disease and i can i see the point that if you have more substantial liver disease um but those are very tiny and it's just again i don't have your experience and i know we're all we're all kind of creatures of where we trained in our experience so um if you have experience in house of you you tend to pattern your your treatment course for that but understand as patients that this is a gray area um that the when to do cytoreductive nephrectomy we don't want to offer that that type of procedure to patients who who um aren't going to do well with opera recovery from the operation so it's very very tough sometimes all right so let's just have a show of hands who would do cytoreductive nephrectomy upfront cytoreductive nephrectomy and who would not it's good so we're all in agreement excellent no i i i want to comment this patient is only 49 you know he has lots of tumors in the body uh he has good performance status you know if you theoretically if you remove a large burden of tumor in the from the patient's body he might do well i know you know the data show that patients with liver metastasis will not do very well but you know considering his age considering his doing really well considering this physiology you know i would i would give it a try if my surgeon colleagues agree with me so i think it's not the the fact that you're not going to offer the patient surgery at all it's whether you do it upfront or you do it after a certain number of cycles of systemic therapy to assure yourself that the disease is not rapidly progressing and then you could do a delayed nephrectomy i mean that's the whole argument about the uh uh third time trial is the timing of the nephrectomy is it upfront or is it delayed and i think this somebody with liver mats whether large or small i mean if there are multiple uh i would uh be concerned about the possibility of this patient having uh rapidly progressive disease uh you know post up you know six weeks later to allow healing unless the patient is having you know uh you know refractory uh continuous gross immature pain and then you do it in a palliative manner and advising the patient that there is a chance that the patient will have progressive disease postoperatively and then uh you know if you uh you know want to give the patient high dose r2 you believe in high dose r2 you work at a center where or the patient has access to a center that is experienced in giving high dose r2 and you think this is what you're going to treat the patient with upfront then that's an argument for doing upfront cytokinectorectomy is to send the patient for high dose r2 you know the it's a great case because i think i definitely get very concerned when i see liver metastasis but i think tom makes a really good point um you know the other thing we know is that when you can we can remove the overwhelming bulk of disease those patients do better that's based on sort of very limited and biased data but still that's what we have what i do want to bring up and i hope i'm not taking your fire chris but it's the the cope with the criteria that actually you developed with steve cope and what what chris did here was they identified six factors that and if you had basically more than three of them correct if you had more than three of them then you as a patient you would not really benefit from surgery and as best as i can tell this patient has one or two of those one the liver and just liver anemia anemia wasn't in the list right yeah so and those uh those factors were lymph nodes in the abdomen lymph nodes in the chest uh several blood markers that were high um what else was it ldh and alfos and liver disease and and the presence of symptoms from metastasis yeah so in that sense in terms of looking for other pieces of evidence to guide you you know i normally would not recommend cytoreductive surgery for someone with liver mets but they are very small and it's a young patient who's going to recover pretty speedily from a big operation and so i actually in this case would offer that was my rationale for offering surgery first so from my perspective liver mets do make me nervous and regardless of the small volume of disease it can rapidly become a high volume disease very quickly and i think it's interesting that you know dr teneer waxed philosophically about why he would not send this patient for cytoreductive nephrectomy it's actually his patient and he sent him to me for cytoreductive nephrectomy um but the goal was to enroll him in the ADAPT trial which you've heard about earlier today uh the ADAPT trial is uh a trial where patients are randomized to receive a personalized dendritic cell vaccine basically their tremors process to make a vaccine uh plus in it versus in it and below and so we both felt that this young gentleman with low volume disease vast majority could be removed with nephrectomy that we would sort of break our position on on cytoreductive nephrectomy in the presence of liver metastases and and offer him this so we took him to surgery we did the left side of reductive nephrectomy and also biopsy one of the nodules in the liver it did turn out to be positive for metastatic disease uh his um final stage was t3a n0 m1 firman's grade 3 so it just means locally advanced tumor with metastatic disease clear cell histology and he comes back now in follow-up and you can see that those tiny little white blushes have become innumerable so he's got extensive disease present all these little white spots are all metastases in his liver so he has progressed significantly which we expect after cytoreductive surgery he's also incidentally got a little tiny renal mass right here which we didn't do anything about at the time of surgery and just uh would recommend continue to follow uh and his lung disease really hasn't uh changed dramatically um there's you know the same small spots there's same number of small spots but hasn't changed significantly there is some enlargement of hyaluronodes so basically some lymph nodes in the mediastinum have increased in size that were not increased in size prior to surgery so um Dr. Taneer this patient comes back to you at six weeks with these findings what are your recommendations for him so he rolled him on the trial so uh he's so you wouldn't change that recommendation you would keep him on I mean depends did he develop also now hypercalcemia high serum elevation of his high serum at the age so I think we already enrolled him in the trial that was the motivation to break the rule and do the upfront diffraction because we have a exciting trial with the vaccine and to do to be eligible for the trial you had to not start systemic therapy but harvest the kidney to harvest the uh to to produce the vaccine to allow the patient to get uh sunetin a plus vaccine so that was the reason we broke the rule here so I think if unless the performance status declines this precipitously unless he's developing now porous features with high serum ldh high serum calcium uh high platelets high white blood cell count if if he did not develop these uh uh poor prognosis uh uh factors then I think uh proceeding with sunetin a plus the the our any vaccine all right time you don't have this trial at your center what would you offer that trials great trial um we just didn't choose just because of logistical reasons with with the urology department but but that trial is great because you're not denying patients act um an act of drug which is currently the standard um so suninib um there's nothing proven better than that agent at shrinking the tumor and so on on the trial you mentioned they get that regardless the vaccine's just a plus so in standard practice outside of a clinical trial setting um they would um most likely either get suninib or votrant um that's a standard okay Brian you look like you want to say something I'm just going to comment just to make sure that people are aware of the you know at a 49 year old with the outcome of surgery is no complication and things went well and in six weeks he's going on therapy you know you probably didn't lose too much but in the setting of where if this were an older patient maybe poor nutritional status even if they didn't meet the risk factors I mean this could be detrimental if this patient had a one complication or a fascial dehiscence or was delayed therapy by months before while those liver meds progressed so um you know we obviously are taking all that to account when we're thinking about these things but I mean I think it's really important that we impress upon the importance of um of looking at kind of the the risk for the of the surgery itself and whether or not these patients are going to be delayed therapy that's active yeah from my perspective in the absence of a clinical trial that this patient was going to be directed towards I probably would not have offered him cytoreductive surgery I would have offered him systemic therapy up front with possible delayed cytoreductive surgery if they had a good response that would have been my approach in this patient yeah I don't know that one's right over the other but I would have agreed with you I would have done the same thing but um I work with nothing right I wouldn't have all right let's do one more case and then we'll break that which I've gone get the lunches and bring them back in here and we'll continue on with the case presentations while we eat lunch uh so this is uh this is an interesting case this is a 72 year old African American gentleman initially presented to an outside physician back in 2003 with an incidental finding of a left renal mass and he underwent left partial refractomy margins were negative it was a type 2 papillary T1a tumor so stage one type 2 papillary tumor a node dissection was not done at the time of surgery he did well until 2007 and then he developed a left renal recurrence and he underwent a salvage left radical nephrectomy at the time the left adrenal gland was left in situ because it was radiographically and phenotypically normal at the time of surgery and the final pathology demonstrated a type 2 papillary right renal cell carcinoma stage T1b with negative margins he did well until 2009 and then he developed an enlarging mass in the right adrenal gland and he underwent a right adrenalectomy thank god we spared that left adrenal and this revealed metastatic type 2 papillary renal cell carcinoma he did well until 2010 and then he developed a right adrenal mass sorry right adrenal fossa recurrence as well as a left adrenal mass and he comes to MD Anderson his past medical history is fairly extensive he has a history of hypertension and ulcerative colitis he's had innumerable surgeries he's had a total abdominal coletomy for his ulcerative colitis he's had a left partial nephrectomy a left radical nephrectomy a right adrenal ectomy he's had lung surgery in the past for a benign tumor and he's had a chirp or a perception of the prostate you could see the medicines he's on he does have a smoking history but quit back in 2003 and he has fairly significant renal insufficiency following his nephrectomy because of the hypertension and so his his scans could not be done with contrast they had to be done without contrast but just to show you so here's the vena cava here's the aorta he's got this mass present where the right adrenal gland used to be which is a recurrence in the right adrenal fossa and he also has this locally advanced mass here where the left adrenal gland should be you can see this is the pancreas draped over it here's the beginning of the spleen but the pancreas is sort of intimately involved with it very large mass and here you can see the extent of the mass extending down along the aorta so again he has an adrenal fossa recurrence after adrenal ectomy and he has what looks to be a locally advanced left adrenal metastasis with extension down along the lateral aspect of the vena cava and has probably a significant chance of having a hostile abdomen from all of the surgery that he's had done in the past and he comes down to the Anderson and sits down with dr. Chapin and dr. Chapin what are your recommendations for this patient it's obviously a difficult problem i mean the um in patients who've had retroprenia recurrences who undergo re-resection i mean there is a real mortality risk dying of the operation itself or dying while in the hospital um this patient's had multiple abdominal surgeries would it be a difficult at best even to get access you're also dealing with other organs that are assumed to be involved with the tumor at this time although in the absence of other metastatic disease a lot of this appears to be local tumor so i honestly it'd be a difficult problem and i probably would see consultation from you you're killing me and i would i'm i'm i'm not i'm not in the hospital i'm i'm traveling so um you're on your own what are you gonna do um you know i i there's not really good systemic therapy for this and in the absence of distant disease i mean i think if the patient wants to to go for it you tend to be heroic here and try to go for it but uh so i'd be very hesitant this is progressing while you're talking why don't you tell us what you're gonna do i probably would seek the help of some of my surgeon colleagues for hepatobiliary just to make sure i don't need assistance with the pancreas and uh i would do a midline approach to resect his left fossa recurrence and his right adrenal recurrence adrenal fossa recurrence okay and he would not have any adrenal glands left so what what are the implications of that he'd have to be on on replacement therapy which is uh mineral corticoid and the glupin corticoid so prednisone in florida for the rest of his life for yeah what's left of dr crumb dr chappan's office next to yours uh he comes by for consultation what would you tell him just a quick question is this something significant here or just a little artifact i don't know guys i have two pictures to look at so since you've seen the films just to see if it's a local recurrence but i just want to close it is so if the first thing to do is to make sure that to do a complete metastatic work up so which we've done and it's negative to summarize it if the patient is healthy enough and willing to take the risk of doing an operation um in the absence of metastatic disease and in the absence of effective drugs his only chance of prolonging his life is to go back to surgery and removing the left adrenal gland and the recurrence on the right side completely to find healthy enough because because he's got renal insufficiency to the point that he can't get contrast for ct and he's got a history of hypertension and had multiple abdominal surgeries but that's that healthy to you yes and in our clinics i mean this is standard so if the patient what we normally do is send our patients to the internal medicine clinic for evaluation before major surgery and if the patient can tolerate an operation and it's his only chance of survival then that's what we have to do okay there's another another look for you to see so i didn't know that one thing to point out about his disease kinetics is you know his disease was fairly indolent over the course of about the first seven years and then suddenly in the past this recurred within a year right last surgery was 2009 yeah this was 2010 so i think that's a that's something to make note of because it's for whatever reason the tumor had a genetic shift or something and now it's not quite as you know it's sort of sputtering along over the course of six seven years and and now with the course of one year it did more than it did the previous you know six okay so what would you do oh i'd actually would call nizar because i i would be in you know he's got a lot of experience with unconventional histologies or non-clear cell and see if there's either a clinical trial or there's something off trial that may be worth trying but uh that does not negate anything that dr carum said his real chance is surgery but the fact is the likelihood is is that he would recur pretty quickly afterward um but i would still you know explore all possibilities with nizar so as it turns out he has fairly significant renal insufficiency with the gfr of 27 he is an emigrate because alfos is minimally elevated but his bone scan is negative and the patient says all right you know what i'm really tired of having surgery so uh dr tenir uh he comes over to your clinic what are you gonna tell him unfortunately he is not a candidate for a clinical trial because of his renal insufficiency so as we discussed this morning uh all these good therapies that we have uh unfortunately there is really they're not established or they're not they have not been demonstrated to be effective in the non-clear cell histology especially papillary type two papillary type two uh in my opinion my experience uh is one of the toughest ones to to treat uh there have been retrospective studies we did a single arm uh phase two trial in non-clear cell and we had 27 patients with papillary RCC uh we treated with sunitinib on phase two trial and the results uh were not uh impressive at all in fact of the 27 patients with papillary treated with sunitinib um zero responded and the median progression free survival was 1.6 months we published this in 2012 in european neurology now some of these patients may maybe may maybe were like uh him with comorbid illnesses some may have had performance stats of two uh but these drugs that we discussed this morning don't really produce the results that uh we see with clear cell so i would uh try to convince the patient and convince the surgeon to go and do surgery now if he's adamant against have surgery uh he's adamant then then we will try uh try sunitinib uh you know for sunitinib would be your first choice well i will try to see if his insurance would cover uh off-label drugs is independently wealthy you can cover it by whatever so why don't you tell us what you would choose well i think the the the drug that tom mentioned this morning uh cometric or uh cabuzantinib would be uh a drug that i would consider uh you know tarsiva urlotinib has been shown to have some activity in what he wants to know what dr teneer would recommend i would recommend if his insurance would cover uh cabuzantinib then we'll get him cabuzantinib okay and if he's indigent what would you recommend then uh you know again if he's not going to be able to get urlotinib or cabuzantinib then uh uh what did you tell us about his performance status as well and performance status is one yeah i mean then you can try sunitinib and and and tell him that the results are not uh that good but we can try that okay there's one other option what's that that is to either use his archival tissue or do a biopsy and have it go through the uh in our group it would be the phase one group or the molecular markers group and um you know basically what happens now is that it's so much easier to test for the gene mutations in these tumors and now what in fact we just got an email this week where they've been able to go from instead of testing 50 they can test 400 known mutations and some of those mutations are targetable meaning that there's drugs that will act against that so that would be another option and actually i think he would fit that um that trial jj had you you and i have done a couple of cases like this what's that i totally agree with you however phase one we're declining him up front because his kidney function is low so but uh even in that case you can still uh do the xm sequencing uh his primary type two so it's uh possible that he has cmed mutation and if that's the case just like what doctor to near said we can try uh covers that in it which is a cmed inhibitor so if you can match the mutation with the drug and the likelihood likelihood for success can be up to you know 70 percent um so okay so your so your choice would be covers that in it if you can get it otherwise um otherwise i mean you can try one of the tki's you know yeah what one do you want to try i would uh agree with doctor to near try uh son internet okay tom any different thoughts no all the above i tend to um use nexivar um a lot for my non-traditional histologies that don't fit any other pigeonhole for anything and um with anecdotal evidence of some people do well for long periods of time and one strategy in the sky who's not going to do well he has a lot of negative features up front with his disease his past medical history his borderline renal insufficiency i mean he's in 2 point gfr of 27 for you all in the room the normal should be in the 60 to 70 range um for someone so he has impaired kidney function he probably my concerns going to surgery right away is that he wouldn't make it through the surgery he'd come up with a complication so one of the things that could stratifies if you put him on an agent and he was had a period of stable disease um that you could contemplate um some type of resection later because at least you know that his his he wasn't exploding because it seems like my experience has been whenever we've taken patients for multiple metastectomies that um one of the biggest concerns is it just pops right up again and it's spreading while you're recovering um and so if you could if you if he was able to demonstrate control on a targeted therapy although that may be rare not common maybe one in five um but if he declared himself that way um then you he may have a chance um with being more aggressive surgically okay thankfully his disease hasn't progressed while you guys have been battling on up here um he was initially treated with synitinib stable disease progression in five months changed to everlimus stable disease significant toxicity noted with both the synitinib as well as the emberlimus um what do you think cut cut cut cut cut cut him he may not think surgery is so bad now after getting all that poison anybody disagree with taking him to surgery okay he was taken to the operating room had an exploratory lap left a radical adrenalectomy excision of the right retroperitoneal mass uh it was actually invading into the gallbladder so you're on block polycystectomy and also partial hepatectomy um this was done in April of 2011 you can see the pathology thankfully had a good surgeon so he recovered nicely from surgery and did well until October of 2013 he then uh showed up on staging evaluation to have a para aortic renal recurrence with CT chest and bone scan that were negative his cratin is kidney functions even worse with a GFR of 23 crating of 3.19 although he's no therapy after surgery or no would you have given him therapy after surgery well I wouldn't have done it that would be somewhat malpractice but I would be curious because most of the time the medical oncologist would like to give more he uh so well okay let's ask him Dr. Tenir would you have given this guy's uh Tom said no no as I said I was arguing for surgery all the way but no I think after the surgery you rendered him without evidence of disease you resected everything visible in the abdomen so I would have followed him like you did so would anybody have given him systemic therapy after the surgery no okay good all right so um here's his uh here's his films and you can see I'll show the audience here he's got this one little area of recurrence right here right next to the aorta uh his kidney functions even worse and he has an even more hostile abdomen because of his previous multiple multiple surgeries so again brief please Dr let's see Dr. Mateen what would you do well he had a reasonable response to the first couple of agents um and so I would uh again call Tom or uh these are and talk to them about putting him back on therapy an alternative would be to observe him for a short period of time just to see if he's developing explosive disease just to spare him you know um the suffering but the suffering of what treatment are you doing surgery no no I wouldn't offer surgery you would not offer surgery okay Dr. Karam so now it's been two and a half years since his last operation it's been three years actually three years so I mean I agree with what Dr. Mateen said the other thing is I would consult with my interventional radiology colleagues to see if there is any way they can do an ablation on this mass I know it's very close to the aorta but at least it's a question worth asking during the course of the disease while it's still small or if it can even be shrunken you do realize this is small ball right here sitting on top of it well can't see it it's pretty dark and I have one picture to look at but if you say so I'll take your word for it it is trust me uh but that's the only other thing I would not go back to do surgery at this point okay Dr. Chapin yeah I mean the same same as what the other two said I mean essentially systemic but sending back to Dr. Tenier for consideration of systemic treatments and then see where things go over the next course of the next year so for this solitary small recurrence in the retroperitoneum all the surgeons say no medical and college anybody in medical and college do you want to do surgery I think the same is surgery for today so I'm sorry I said it again the theme is surgery today so you would offer surgery well at least some local intervention if it's possible you know I don't I don't know if if you repeat like those target agents whether they you know the tumor apparently didn't respond it became refractory if you treat I don't know the you know how much chance you have for this to respond yeah so to be honest with you from my perspective he did not tolerate the targeted therapy as well he had a lot of toxicity his renal function is terrible this is a small isolated recurrence we took him to surgery and he had a salvage resection there's the pathology margins are all negative he also took out some of the lymph nodes and you know it's been three months so far so good he was able to get through the surgery fairly well but I thought my feeling at the time was that you know additional systemic therapy we know what this thing is it's not going to shrink it's not going to make it go away it's going to make him feel terrible and probably make him a worse surgical candidate so you know I thought that the aggressive local resection was probably the best way to go all right so why don't we take just literally five minutes to run out and get some lunch and then bring it back in here and then we'll continue the grilling and then you know so You're welcome to bring your lunch if you want, we know you eat, we've had a good time. You're welcome to bring your lunch if you want, we know you eat. We've had a few casualties. So one of the things we're remiss about, it's my fault and I apologize, but did anyone have any questions that they wanted to ask? I was asked one question during the break that I just wanted to allude to and that is, you know, one of the concerns when you integrate systemic therapy with surgery is the issues of wound healing, which I brought up during my talk. And, you know, it's very important to understand that when you commit to performing a surgical procedure on a patient, they are going to need somewhere between four and six weeks of time to recover from that surgery before they can get any targeted therapy, regardless of what's going on. And that's always, at times, not always, but at times it can be a real crapshoot where, you know, you'll have a patient that you operate on whose disease for whatever reasons decides to explode after surgery and you sit there and you watch this disease consume this person and there's really almost nothing you can do because of the dangers associated with receiving targeted therapy and the issues associated with wound healing. Did anyone else have any other questions? If you do, we'd ask you to come to the microphone just so that we can record the question. Do you have a question? Anyone? If not, we'll proceed with some more cases. And, you know, if questions do come up, please don't hesitate to get up and come to the microphone and we'd be happy to take those questions at any time. If you have a question about the case, or if you have a question about one of these guys' judgment, just step up to the mic and let us know. All right, with that said, why don't we go ahead and move on? So the next case is a 50-year-old gentleman who presents with shortness of breath and chest pain. Those are sort of classic symptoms for somebody who has a pulmonary embolism that's always a concern. He reports a 60-pound weight loss and fatigue over the last six months. He had a CT which was negative for metastatic disease, but also negative for pulmonary embolism, importantly. He has some evidence of renal insufficiency with a creatinine of 1.49 GFR of 50. He's got some anemia, although his LDH and LFTs are all within normal limits. LFT stands for liver function test. LDH is lactate dehydrogenase, which is just a blood test that we get an enzyme that circulates in the blood. And here are his films. So what we can see is he appears to have a tumor originating in the right kidney. And this is a tumor thrombus that extends up the vena cava all the way into the heart. Here's the heart right here. And you can see that he's got a very large tumor thrombus present within the right atrium, which is one of the chambers of the heart. Here's another view, which again shows a locally advanced tumor involving the right kidney here with a thrombus going up to the heart. And here's a cross-sectional image. Here's the renal artery going to the kidney. Here's the tumor invading into the vena cava right here and a locally advanced tumor involving the right kidney. The left kidney appears to be normal and his metastatic evaluation appears to be negative. So with that said, Dr. Karam, you're always whining that you don't have enough patients at clinics. So this guy shows up in clinic for you. What are you going to do? Write an ephrectomy and IVC thrombectomy and atrial thrombectomy in conjunction with our vascular surgery colleagues. Okay. What would your approach be? What incision would you make? I would do a midline incision and then the vascular surgeon might decide to do a sternotomy if they cannot get the heart thrombus from the abdomen. So that will be one long incision basically from the neck down all the way to the pubic bone. Okay. But it could be done in different ways, but that's the approach I would do. Okay. Dr. Chapin, presumably you're allowed to do this. What would be your approach? Yeah. So in conjunction with you or Dr. Karam or Dr. Matin, I would perform a right radical and an ephrectomy and thrombectomy with the help of the vascular team. Again, I do the same through a midline approach. In the absence of, you know, we talk about lymph node dissections and you're probably either going to bring that up or if you haven't already, I would do a lymph node dissection and this just as a function of trying to dissect out the vessels anyway. Would anybody consider preoperative embolization? So just for the audience, preoperative embolization means that just prior to surgery, basically putting a cork in the renal artery to cut up blood flow to the kidney with the tumor in it. And in past series, that is actually that used to be the sort of standard approach for this type of this type of a tumor. Would anyone consider it? No. Okay. In the old days we used to do that and the thought process behind it was that these tumor thrombi are very vascular. And so by cutting up blood flow to the tumor thrombus, the hope was that you could get it to shrink down and avoid the complications associated with having a median sternotomy and having to be put on cardiopulmonary bypass and so forth. And there are anecdotes in the literature where you'll see this tumor thrombus much like this that shrinks way, way down almost to the renal vein. The problem is that that almost never happens. And so the morbidity or the side effects associated with embolization are probably not worth the potential benefits. And so we rarely, if ever, will embolize patients nowadays before surgery. Can I ask you if the patient had compromised liver function, would you do it in that scenario? Not in the setting of planning to do the operation, but in the setting of trying to treat what's there? That's a good question. I'll throw that one over to Dr. Karam. What do you think? So I had this in my presentation, but just for the sake of time I didn't include it. So what you're referring to is when the tumor thrombus and the vena cava goes to the veins of the liver and basically blocks the liver outflow. And that's called Bud Kiari syndrome. And for those patients, we routinely do not take them to surgery immediately, but we first do the embolization procedure to try to shrink the tumor from those veins and allow the liver to recover. And then if they recover well, we will take them to do the operation. Yeah, so in our experience with Bud Kiari syndrome, and Bud Kiari, Bud was a doctor, and Kiari was a doctor who described the syndrome. It's a hepatic outflow obstruction associated with abnormalities in LFTs. They develop abdominal ascites. They develop lower extremity edema. And they develop liver profusion abnormalities, clotting factors that the liver produced become abnormal. And in our experience with taking these patients to surgery, the in-hospital mortality rate is in excess of 80%, meaning that 80% of the time these patients that never leave the hospital, they die in the hospital. So now we approach them with this embolization process, again, hoping that the tumor thrombus is vascular, hoping that it shrinks a little bit so that they can again regain hepatic outflow and return their liver function to normal. The problem with embolization, however, is that if you do not operate within the first 48 hours after embolization, you have to wait three months. And the reason for that is that the changes that occur as a consequence of embolization and the abdomen, it's like a bomb went off in there. And the tissue planes are basically like wet Kleenex. So trying to take somebody to the operating room before the embolization has had time to mature can be a catastrophe. How successful is this embolization? It's hard to say because, you know, the only ones we know about are the success stories. The ones that are not successful usually go home and die and we don't hear about them. So this patient underwent right radical nephrectomy, IBC thrombectomy. You can see the pathology here. He had evidence of rabdoid features. That sounds bad. 20 to 30 percent. And it was a T3C tumor obviously because it was up to the renal, up to the right atrium. No evidence of any adenopathy. Dr. Karam, rabdoid. Sounds weird.  And you hear in this situation is clear cell kidney cancer. You could see it alone or you could see it with another very aggressive tumor called sarcomatoid. These are all very high grade tumors, you know, grade three or four. And they basically all it's saying here we have a patient who has an advanced tumor going all the way to the heart and high grade tumor. So this patient is at a very high risk of recurrence in the future, which, you know, goes down to your question there.  Unless there's an adjuvant clinical trial, the standard would be to just watch the patient with imaging, which we would do every three months or so the first year. If he wants to know his risk of recurrence, what number are you going to tell him? I'd say at least 50 percent. 50 percent risk of recurrence? At least. Dr. Matin, you agree with that? Yes, perfectly. Anybody else have any differing opinion? Sarcomatoid is really different from sarcomatoid. And all it says, this is a high grade tumor. It is, like, chose the tumor cells around, but it is different than sarcomatoid. All it says is basically high grade. Okay. So here's a 53-year-old white female who presents with low back pain and weight loss. She has a past medical history significant preservical cancer, which was treated with a cone biopsy.  All of her laboratory studies are within normal limits. And here's her films. So there's a couple of points here. You can see she's got a tumor involving her right kidney. You can see that here in the cross-section. But she's also got evidence of sacral involvement. You can see she's got a lesion right there. And we'll see that on the next film. Again, you can see she's got tumor involving her sacrum. So it's a metastasis from the kidney tumor. Well, presumably a metastasis from the kidney tumor to the sacrum. You can see it again here. Everyone appreciate that? Okay. So first I'll throw it out to Dr. Gao. This patient shows up in your clinic. What are you going to tell him? First of all, you want to make sure the diagnosis. So she has a history of cervical cancer. I assume that's an early stage, but still with two sides of disease. So you want to... I would biopsy of that sacrum mass. So you would biopsy of the sacral mass? Yeah. Or mass, okay. Dr. Krom, do you agree with that approach? Yes. So you would biopsy of the sacrum mass? Yes. Dr. Tenier, this is actually your patient. What did you do? Yes, I would biopsy. Either the mass in the kidney or the sacrum mass. Okay. Here's the bone scan. And again, that just demonstrates just for you all. The hotspot right here corresponds to the area of uptake or the area of concern on the CT scan, indicating that it might represent a metastasis. So everyone has said that they would do a biopsy. Anybody differ from that? I would just... We definitely want to biopsy of the sacrum mass over the kidney primarily. That would be my choice. Yeah, the problem... Nobody actually did... You didn't do a biopsy. No. She was... It was presumed that this represented metastasis. And I guess I'm... You know, cervical cancer metastasizing to bone and as well as to the kidney. I think that's... I'm not even like... I'm less concerned about the cervix since it was treated with the comb biopsy, but something else. Like? Like another primary. Like? Primary bone sarcoma or osteo... Bone sarcoma metastasizing to the kidney? No, I think that could be two separate primaries. Okay. But I'd want to know what the sacral lesion was before I went ahead with treating the kidney. Why? Because if it turned out that it was metastatic kidney, then there is possibly options for clinical trial in like a pre-surgical type setting. Sarcoma and the patient needs kidney function for chemotherapy for sarcoma, then I would treat the sarcoma with chemo first and then do that effect to me at a later time. But the chance of this being another primary, it's always yes in the partial diagnosis, but that's practically, practically speaking, this is very unlikely to be anything else but renal cell would match to the sacrum. I mean, this is a pattern of behavior of RCC. It's unlikely. We've seen, I mean, we've seen we have patients together the patient has multiple lymph node enlargement up and down, you know, from the chest all the way to the pelvis and has renal mass. Yes, there you would see one of those lymph nodes because the patient could have very well a lymphoma and a renal concurrently. I see all the time two malignancies concurrent. Both sometimes can be metastatic, but this is not, it's unlikely to be something else other than kidney going to the sacrum. We have a saying in medicine or in med school you learn said, the saying goes, when you hear hoof beats, think horses, not zebras. Apparently Dr. Karam and Dr. Chapin didn't go to that medical school. But we work here at MD Anderson. So the patient subsequently was referred to me and I don't want to set a reductive nefrectomy. She received radiation therapy to her pelvis for the pelvis metastasis and her tumor was sent for processing and she too is being enrolled in the ADAPT trial which is again the dendritic cell vaccine plus synidine versus synidine below. Jose and I have a question to ask you. Would you have considered doing a partial nefrectomy in that patient? That was what I was going to ask you actually. Yes, I would have, that's why I'm asking. Going back. So Dr. Karam, I believe you have published or just now publishing the role of partial nefrectomy in metastatic disease. What is the role of partial nefrectomy in the setting of metastatic disease? The application that we just have is a small number of patients over a long duration. It's about 33 patients but the bottom line is whenever it's technically feasible to do a partial nefrectomy that's not a heroic type of partial nefrectomy and this is a feasible partial nefrectomy we should consider it especially if the patient has borderline kidney function. Okay, so this patient doesn't have borderline kidney functions. She has normal contralateral kidney. So, you know, I agree with you you could do a partial nefrectomy here. So there's two, I have two challenges, two things that occur to me for that because I did consider it. So first of all, it would probably be would you do it robotically or would you do it open? This looks like it's do robotically based on this picture. I mean it looks like it's not invading into anything like a collecting system but... You would not do this robotically. No, you would not. Having said that, when we talk to the patient with a metastatic disease about a partial nefrectomy we have to be very careful and tell them that there is a higher risk of complications with partial nefrectomies. So that might delay their receiving targeted therapy. So if we are doing a partial I think we have to be sure that we can do a good partial with the lowest possible complication rate so that we don't mess their chances in getting a clinical trial. So if it's a large mass invading into other things I would definitely do a partial but for things that are doable I think we should at least entertain the idea. My approach would largely rest on whether or not I was planning on doing a lymph node dissection at the time and in the setting of metastatic disease I think there's a lot of thoughts about whether or not you do a lymph node dissection I think in this patient my thought is in this patient with a solitary metastasis doing a lymph node dissection would be negative. If your plan is to treat that metastasis possible with a resection later on by metastasectomy. Do you think that metastasis is resectable? No I don't think it is at this point but you could treat it locally. My point is in the absence of other metastatic sites I think a lymph node dissection may provide some information here. And then the patient develops callous societies and has a drain. Sure there's risks with everything. She had a radical would have absolutely done a partial would have done a robotic. The challenge with that though is again going back to the statement that I made before we started the case presentations again if she has a complication urine leak bleed what have you that could potentially prevent her from getting systemic therapy for some period of time because you're going to need to have the urine leak heal up beforehand. So if she had a complication related to the partial I think we're overstating those complications you know I mean urine leaks are very unusual in our practice these days. Not with a tumor that size. And you know the overwhelming majority of the kidney is uninvolved by tumor. You have 90% of the kidney which is completely healthy. You know the real risk would be hemorrhage but hemorrhage is something we can manage fairly quickly and I don't think it would delay her therapy overtly. So that would be my approach. I would agree that if it's that's pretty clear cut that that's separate. I think that that would be on the lower end of the complication rate compared to something that was maybe a very endophytic or tumor that's inside the capsule of the kidney and not really extending outside of the kidney. So I think that's a scenario where it might be an option. I agree I'm not a surgeon but I agree a portion of rectomy would have been the preferred approach for treating the primary and I would not do lymph known dissection in the space with metastatic disease to bone absence of obvious enlarged lymph nodes by CT or at the time of surgery. So that's added time and it's really not going to help her to have RPLND in her case. And so the thought again the thought process from my perspective was we could do a minimally invasive procedure that she's much likely to recover from very rapidly and go on to receive systemic therapy if she needed it if she didn't need it she could just be observed. So let's move on. She presents with cough, lower extremia edema. No real urologic complaints. Lab work indicates hypercalcemia and anemia imaging is obtained. She has a performance status of 1. She has a past history of myasthenia gravus gastroesophageal reflex disease and also ADHD. She's had a C-section and had a thymectomy C-section times 3 in my thymectomy in the past for her myasthenia gravus. And here's a locally advanced tumor involving the right kidney with an IBC thrombus. And again, not to belabor this. Dr. Karam, how would you approach this? Does she have any metastatic disease? CT chest was negative, bone scan was negative. So the patient has poor risk disease with the kidney being there and then having at least two lab functions abnormal. This is no metastatic disease. What do you mean she has poor risk disease? Yeah. I mean just the poor risk features with the other lab studies but I think surgery would be her best option here. But then a frectomy and thrombectomy. Okay, would you do another section? Yeah, I mean for thrombectomies it would be part of the procedure to free up the vessel. So we would do an lymph node dissection as part of the operation for all the IBC or most of the IBC thrombi. Is her lower extremity edema because of compression or IBC syndrome? Or does she have also hypoalbuminemia? Do we know her serum albumin? Serum albumin is normal. So yeah, the lower extremity edema is just related to back pressure from the IBC. So she underwent a radical nephrectomy and she had greater than 95% sarcomatoid slash rabdoid de-differentiation. The tumor was invading into the renal vein and also into the arterial wall and was present at the margin of her section. So Dr. Chapin, how would you follow this patient? What would you recommend for her? Yeah, this is unfortunate because of the sarcomatoid findings, but also the fact that you have a positive margin. There's a very high likelihood of recurrence, whether it be at that margin or whether it be in the FOSSA or whether it be dis-in-disease. So I would do what I do for most high-risk patients. If there wasn't a trial available I would follow them closely with the six-week follow-up imaging followed by probably every three-month imaging as well. Okay. Dr. Crom, you agree? Yeah, about the follow-up I would do the same just follow-up at six weeks because these patients have a very high chance of recurring early, but unfortunately this patient probably doesn't qualify for clinical trials even if we had them because of the arterial margin, which we don't see arterial margins uncommonly at all in kidney cancer, but with sarcomatoid that's not surprising at all. So I would just follow her, like Brian said, six weeks initially in every three months. Dr. Matin, anything? No different. Medical oncologist, any role for systemic therapy here in this setting? Not of protocol. And if he is not a candidate for improv because of the positive surgical margin then we will follow her as mentioned, three months post up with scans and then I think with this histology I would probably get at least three scans per year maybe even four scans per year every three months. Dr. Crom, what would you assess this lady's risk of having her tumor come back? Unfortunately I think it's more than 90% chance of it coming back. And where would it come back if it comes back? With the sarcomatoid it will probably come back at the renal fossa, the lymph nodes, the liver and the lung among other places. This is a very aggressive tumor and unfortunately it comes back quickly, typically within the first six months. Dr. Chapin? I think it's inevitable that there's going to be a recurrence when you see sarcomatoid like Dr. Crom says. I know you're presenting some of that data today but I think it's pretty much when? The tumor is already inside her body right? The surgical margin is positive so specifically this will come back. So the good news is I just saw this lady in clinic last week and she's now one year out and no evidence of the current disease. Good for her. So far so good. Okay, here's a 78-year-old with an incident on renal mass. She has a history of breast cancer and the mass was discovered during her surveillance for breast cancer. She has some significant history. Hypertension, diabetes, hypothyroidism, atrial fibrillation, depression. You can see the medications that she's currently taking. She has a negative metastatic workup. Her labs are within normal limits and she has a GFR of 50. And you can see she has a local localized renal mass involving the anterior aspect of her right kidney. So briefly let's go down the line. What do you recommend for this patient? So she has no metastatic disease. No metastatic disease. This is a small SRM, small renal mass. She has 78 and multiple comorbidities. This is a patient I would follow surveillance. Now I understand my colleagues to the left of me here. Well, the surgeons will say let's biopsy because the patient wants to know. I would not biopsy. It's a small mass and I would just follow her expectantly. I will enroll her on Dr. Martin's surveillance trial. It does not mandate a biopsy. But if it mandates a biopsy it will do the biopsy. But I would definitely offer a surveillance. Okay, Dr. Gao, briefly. I would agree. I would send the patient directly to Dr. Martin. Okay. Would you do a biopsy or no? You know, with her age and the comorbidities I would not. You would not. Dr. Chapin? Biopsy and surveillance if the patient refused, robotic portion. Wait a minute. So you want to do a robotic partial? No, no. Biopsy and surveillance would be my first choice. If the patient refused surveillance I would do a robotic partial. And the surveillance would be regardless of what the biopsy shows? Yeah, for the most part. I still agree because I agree with Dr. Martin and if it was me, I'd want to know. So biopsy is an option. They don't have to do a biopsy but if it was me as the patient, I'd want to know what I had in me. I mean if it came back as a grade 3 tumor, maybe it would change my mind. If it came back as a benign, maybe it would be less frequent imaging but I'd want to know what it was. Okay, Dr. Crom. I would recommend surveillance without a biopsy and then without the biopsy part for two reasons. Number one, she has atrial fibrillation is on anti-coagulation so I don't want to take her off the anti-coagulation to do a biopsy and then we know with the biopsy the grade is not very accurate so it's a hit or miss 50% of time. Biopsy is good to tell us the histology if it's cancer or not or what type of cancer but grade-wise it's not as reliable so I would just observe the patient. Okay, Dr. Matin. The option of biopsy is there and it's really a toss up for the patient. You're not worried about atrial fibrillation. We operate on those patients all the time off anti-coagulation so that's not an issue. I think that Brian makes a good point. He showed that it's an oncocytoma. You know, I would be very comfortable following her much less stringently and which is a benefit for her. She underwent a biopsy which showed an oncocytoma and she's currently being followed. So, moving on, this is a 59-year-old white male who presents with abdominal mass. It's palpable. No urologic symptoms performance that is zero. Had an 8-pound weight loss. All labs within normal limits. MRI of the brain on a negative. You can see a locally advanced tumor involving the left kidney here. Again, locally advanced tumor involving the left kidney. Can you go back to your first slide real quick? Maybe a question of a tumor. Yeah, just the presentation. Okay, weight loss. Okay, I'm sorry. Go on. So there's the locally advanced tumor involving the left kidney and evidence of pulmonary metastases. You can see a spot here. You can see a spot here. You can see a spot here. So would you offer this patient side-reductive nephrectomy? Yes or no? Let's just go down the line. Dr. Tenir? Yes. Dr. Gao? Yes, absolutely. Dr. Yes, and all three of us. No one would offer him pre-surgical therapy? Not all trial. Okay, suppose you had a trial. Would you offer him that? Yeah. Okay, so I'm going to let you in on a little secret. The case is going to turn out very well because actually this patient that we're talking about right now is in this room. Okay, so he's going to have a good result regardless. He enrolled in the synidine pre-surgical trial. He had a biopsy of his lung lesion and revealed metastatic clear cell renal cell carcinoma and he started on synidine. So the pre-surgical trial was where patients received two courses of systemic therapy. Those patients that had stable disease or responded went on to have side-reductive nephrectomy. Those patients that progressed typically we did not offer them surgery. They would instead go on to receive some sort of alternative therapy. And here's the response that he had. He had a fairly good response to it. You can see the sort of central necrosis in the tumor. There's a local extension into some of the retroperitoneal musculature here. And he had basically stable disease, maybe a slight progression in his lung metastases, but still demonstrating a good performance status. So he's got basically stable disease, maybe a little bit of progression in the lung. What do you want to do? Let's go down the line. Do you continue synidinib? Do you take the side-reductive nephrectomy and then continue synidinib? Do you switch to inhibitors, either Everlimus or Temsarylimus? Do you switch to Exitinib? Or do you do the side-reductive nephrectomy and then change the TKI post-op? Dr. Tenir, quickly. I would proceed with the side-reductive nephrectomy and then restage him post-operative. I mean the protocol, that was the spirit of the protocol. Patients after two cycles of synidinib, if they have stable disease or have responded, will proceed on having side-reductive nephrectomy with restaging post-op. If their disease is still stable or minor progression, then they can continue with synidinib. Okay, Dr. Gao. Initially I would not treat this patient, just because a small portion of patients after side-reductive therapy actually have shrinkage of the metastasis. So if he is one of these patients, I will just continue to follow him. However, if he has disease progression, you know, he had very good response to synidinib before surgery. So I would start him on synidinib again if he has disease progression. Drs. Chapin, Garam, Matin, any different thoughts? Number two, I mean the pictures you showed didn't show progressive disease, just showed stable disease for the chest. So I would follow the protocol and do the side-reductive followed by anything different, guys? Number two. So overall assessment was there was slight progression of disease in the lung, but the primary did have a response that you saw. I still had an excellent performance status, so he's taken to the operating room and he underwent a left-radical nephrectomy. He was noted at the time of surgery to have metastasis to the right adrenal, which was resected. And also a diaphragmatic nodule, which revealed metastatic clear cell renal cell carcinoma involving fibromuscular tissue, and you could see that he had a locally advanced tumor involving the left kidney. So you didn't monitor it under an elective? Yeah, I'm reading that. I'm actually... Yeah, we left it.  We just did the mass. I think we left the left adrenal because of the right adrenal mass. Because it says there's surgery left adrenal. No, we just did it. We did a partial adrenal left. We left the adrenal tissue behind. We left the adrenal tissue behind. Post-operatively, he had a superficial wound infection and a psoas abscess that required drainage and antibiotics, and systemic therapy was actually delayed for four months because of the complications associated with surgery. But his disease, thankfully, progressed slowly and he was started on Everolimus. And as I say, he currently is president at this meeting, quite well. Let's do this case. This is a 62-year-old white male with a history of blood in the urine. He has really no significant past medical history. He's got a locally advanced tumor involving his right kidney. You can see it there. And also has bilateral pulmonary nodules. He's got some anemia. He's got an elevated LDH. All his other labs are within normal limits. His bone scan and MRI are negative for all the other labs. So Dr. Gao, what would be your approach to this patient? You know, of course, we need to know the diagnosis of this patient first. So what are you going to do? Sorry, did he have meds to anywhere else? There's bilateral pulmonary nodules locally advanced, right primary tumor and no other evidence of metastatic disease. What are you going to do? I mean, I would still do biopsy to make sure the diagnosis. Okay, what would you biopsy? Biopsy the tumor, the kidney tumor. You biopsy the kidney tumor? Okay, Dr. Taneer, what would you do? I think the concerns here, obviously the reason you're putting this case is there is high serum LDH, which we said, you know, for the audience this is lactate dehydrogenase. It's a measure of tumor burden when it's higher than the upper limit of normal. And some studies show that it is important when it's more than one and a half times upper limit of normal. So in our lab at Amgenison the upper limit normal for LDH is 618. So this is more than one and a half times above the upper limit of normal. So that's a prognostic factor that is an associated negatively with survival. The other thing is anemia. So if you look at the case here you have a patient who has advanced disease with poorest features because he's presenting with advanced disease already at the time of initial diagnosis. He has anemia and he has this high serum LDH. However the bulk of his disease the burden of his disease is in the kidney. So in this patient I would proceed and take the kidney out. I would do cytroductive nephrectomy because to remove the bulk of disease and it's very possible that post removal of this kidney mass that the hemoglobin and the LDH will improve. And then I would treat him post-operatively of course we will know then what the histology is and the histology will guide us in terms of what systemic therapy will offer him. If he has clear cell he's young 62 is relatively young as I said and he has a good organ function and he has no comorbid illnesses then I would offer him high dose interleukin-2 as the curative therapy that we have still right now. If he is not accounted for high dose interleukin-2 then he can get enrolled on one of our trials and he would be if it's clear cell he would be eligible for to enroll on the start trial. So you would not do a biopsy ahead of time you would just send him for surgery? Yes, I think in this particular case like I said I think the bulk disease is in the kidney I would not, it doesn't have what I believe are relative contraindication to upfront nephrectomy and that's performance status of 2 or worse and it's not, I think his PS is 0 or 1 you said. And he does not have brain mess, does not have multiple bone mess, does not have liver mess. So these are the criteria that I use and we both use to decide if we're going to do systemic therapy upfront. He doesn't have as I said brain bone liver he has good performance status then I think surgery is the way to go without biopsy upfront. Okay, Dr. Chapin what are you going to do? I guess I would ask Dr. De Nere a question about his response and if a biopsy were to show papillary or chromophob would you still recommend the seroid nephrectomy in this patient? Yes because again the bulk of the disease is in the kidney even if it isn't a variant histology as you're saying papillary or chromophob. More reason actually for me to do the nephrectomy would be that these other histologies don't have as many systemic therapy options as it is with clear cells. So more reason to do surgery. And so I mean given that answer I typically would not biopsy of this mass unless the person was eligible for pre-op or pre-surgical clinical trial because regardless of the finding you're going to take the kidney out especially in the setting of limited meds to the lung so I would not do a biopsy I would go right to the side of reductive. So I mean certainly this tumor doesn't look like a medullary Casinoma but what if you know if it looks like a renal medullary Casinoma you probably want to know the diagnosis first right? Well I think I'll obviously you can make diagnosis as the patient walks into the clinic before you even look at any scans he's not African-American doesn't have sickle cell trait he's 62 those are not criteria for sickle cell sickle cell will be somebody with sickle trait and with a young age so and blood? Yes sickle cell trait so I mean mostly mostly not African-Americans. Dr. Karam I would choose number three and you would not do a biopsy? No be the ultimate biopsy. Okay Dr. Matin anything different? No. Patient number one said reductive nephrectomy there's a pathology T3A N01 clear cell from his grade four and he shows up six weeks later with modest progression of their pulmonary metastases so Dr. Tanir. Hydrozyl 2 as I said so you would offer the patient Hydrozyl 2 that would be your upfront choice? If again postoperatively the kidney function is good the kidney function is good. Dr. Dao? Yeah you know you want to make sure all the organ functions are okay lung function, heart function, kidney function if it's okay he's relatively young certainly you can talk to the patient about Hydrozyl 2. What would be your recommendation or would that be your recommendation or would you recommend something different? Yeah that would be the first one because actually I always talk to my relatively healthier patients about Hydrozyl 2 therapy even though the response rate is low but that's the only chance. What is the response rate? So the overall response rate is about over 20 percent but the complete response rate is less than 7 percent partial response rate is about 15 percent so if he can achieve complete response rate the chance for him to live up to 10 years will be about 80 percent But his chances of doing that are about 6 in 100 right? That's right so it will be like 7 percent times 90 percent so that would be 5 to 6 percent. Dr. Chapin your thoughts? I mean after extensive counseling I would consider recommending IELT to the patients need to know what they're getting into with that though but I do agree it's the only way that you can potentially have prolonged, durable survivals and cures with this. Okay Dr. Kron? Typically I would refer the patient to our colleagues from medical oncology but IELT sounds like a reasonable approach and we can always give TKI's after IELT when we can't really do it the other way but I wanted to ask Dr. Gao and Dr. Taneer is there any age limit let's say if the patients organs are functioning fine is there any age cut off where you would be more nervous giving IELT? It is more important than age is physiologically age. So if the patient is 70 and is a fit then that's fine. So there's no specific age cut off there? Well obviously we don't give high dosage to people who are 75 and older I think the the oldest patient I know has received high dosage was 75 so beyond that even if they're fit they're not going to be able to tolerate therapy and receive the adequate number of doses so it's unlikely that the therapy is going to benefit them if they only get 3-4 doses instead of you know 8-9 doses per cycle. So I think 75 up to 75 if they're really fit otherwise it's 70 years and they are younger. Yeah they also have all this it's sort of like you know pre-op evaluation you have to go through all this evaluation for organ function such as you know heart function, lung function you have to do a lung function test and if the patient you can just look at the patient you can tell you know whether this patient is going to be okay or not and then you're confirmed with all this objective studies if everything fits well together yeah you go ahead and do it. Dr. Matee? Yeah I mean you know the patient's going to have to make a choice there with taking the chance with IL-2 and the risks associated with it versus something that's you know one of the more modern agents. I think the other thing that I just want to mention is we have a trial that's currently not yet approved but it sort of bridges the gap a little bit with immunotherapy and allows side-reductive nephrectomy but it's actually one where we take patients to get one of their metastases and then shortly thereafter follow it up with one of the agents that Dr. Gau spoke with you about one of the immunotherapy agents. The idea there is that the immunotherapy agents by themselves even though they have some response it hasn't been as great as we think but when you combine it with something that can prime the immune system and set up an inflammatory response that maybe you can really heighten that so that protocol when it opens is approved by our ethics board but the idea there is that we ablate it give them the systemic immunotherapy for a couple of months and then patients come in for side-reductive nephrectomy and then as long as they're doing well they actually continue getting the immunotherapy So Surin on that note what sites are you considering for ablation bone only or are you doing also lung and liver? Yeah so basically anything that interventionalists feel like they can do and as you know they've gotten pretty talented and safe so they can do the lung they can do the lung fairly safely they have good experience with that they have tremendous experience with treating bone lesions they can do soft tissue sites if there's a tumor in the other kidney we could always do that also as part of getting some local control and they're doing liver as well and potentially liver I mean that I think we need to think about there's no specific criteria for that but we certainly would you know the way it's set up is that the urologist interventionalist and medical oncologist would have to be in agreement Have we decided if it is cryo or RFA? Cryo, cryotherapy Cryo So we always laugh about this prior to 2006 when all we had was interleukin 2 and the medical oncologist used to say all we have is this lousy interleukin 2 it doesn't work on anybody the response rates are low and then we get all these new agents approved and then you have them on a panel you show them a case and you ask them what they're looking to Anyway that's our last case and I want to thank the panel for participating in this exercise and I guess I'll one more time ask the audience if you had any questions that needed to be answered Thank you Chris by the way My pleasure I heard a mention about kidney cancer spreading to other organs invading other organs and like nodules in a lung how do you differentiate between this kidney cancer that is spread and lung cancer what's the difference between the two I'll answer first typically when kidney cancer spreads it will spread to multiple sites it's rare to spread to one solitary site that's the first clue secondly when it does spread to that site it typically will have multiple nodules as opposed to just one so if you have a patient who has a locally advanced kidney tumor and multiple bilateral pulmonary nodules it's not lung cancer it's kidney cancer I mean you don't need a biopsy for that but if you have a patient who has a locally advanced kidney tumor and a solitary lung nodule if it has any sort of atypical appearances to it you might want to do a biopsy of that lung nodule to prove that it's metastatic kidney cancer or prove that it's a primary lung cancer so it's really the clinical scenario that represents a primary tumor of the lung versus a metastasis from the kidney usually the lung cancer if the cancer started in the lung has a little different radiographic appearance than kidney cancer spreading to the lungs or any other cancer that's spread to the lungs but you're right it could be that the patient can have two and in fact sometimes we have patients who have two, three or four and it just depends on our suspicion when we look at the scans if we really suspect that we are dealing with now a new cancer we will go ahead and biopsy it I mean I have several patients who have kidney cancer and lung cancer I'm treating in fact a person right now who has both kidney cancer that he's had it for six years that I've been treating him with and then a year ago something didn't look right to me on the CAT scan of his chest and I suspect this was a new cancer that arising in the lung so we biopsyed the lung and it was sure enough square mesocarcinoma of the lung that was just beginning in the right upper lobe and we treated it with radiation so yes we need to be on the lookout or our index of suspicion should be high to say this does not look like it is kidney cancer that's spread to the lung but something else and we biopsy it is it better to have kidney cancer that's spread to a lung compared to having lung cancer or kidney cancer that's spread to a liver compared to liver cancer it depends on the type of lung cancer and liver cancer and it depends on whether these cancers if they if lung cancer is metastasized already metastasized that can be challenging to treat and incurable even though we have systemic therapy options now for lung cancer or liver cancer so I think obviously it's not good to have cancer that's spread to any organ we don't want to do that we don't want to see that but I think there are more options of treatment for a patient with kidney cancer that's spread to the liver and lungs then there are for patients with say primary liver cancer or lung cancer that's spread to liver or other organs okay thank you I would also comment that the reverse is also true you do have tumors that metastasize from other sites to the kidney you could have melanoma that has spread to the kidney breast cancer was one of the topics today that we were reason why some of us were looking at biopsy because we were concerned maybe the breast cancer had metastasized to the kidney it's still breast cancer that's now in the kidney not kidney cancer just because of its location but the origin is what we describe it from so I just wanted to make a couple of comments so over 90% of patients with lung cancer actually are smokers so you can just ask about the smoking history so that will give you another clue the second one to answer your question about which type of cancer will be better so it really depends upon the stage of the cancer so just like kidney cancer if it's at early stage lung cancer is also very easy to treat you can just do biopsy other do surgery and then you can have better outcome of course once they progress to metastatic stage they are both pretty bad okay again we can't thank you enough for coming we hope that you found this informative and somewhat entertaining at least the food was good and I'm going to apologize in advance I have a plane to catch so I'm going to dash on out of here so I'm not ignoring you or running away I just have a plane I have to catch but some of my colleagues will stick around if you have questions that you want to ask them personally and we hopefully will see all of you and even more of you next year thanks very much