 All right, so this is another fun part of this conference. 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 a wide variety of opinions about what to do. And I think it's helpful for patients and families to understand that medicine is an art, not a science. And there is many times no right answer, but it oftentimes is helpful to listen to the physicians going through a process of decision making as they are learning the facts of a case and helps you to better understand sort of where our minds are at the time. 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 program with some cases. We have a STEAM panel of medical oncology and 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, Ms. R. 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, 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 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, all this shiny stuff is metal present in the lady's 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 a 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 in the lateral aspect of the left kidney. It extends down into the central part of the kidney at least appears to have contact with the renal sinus and the collecting system here. And she has a normal contralateral kidney. As I said, her labs are all within normal limits including her renal function. So Dr. Karam, 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? Robotic. You would do it robotically interesting, okay? Yes. Dr. Matin, thank you for joining us. 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 of the chest is negative and she's got that right-sided renal mass. What would be your approach in this patient? What was her kidney function? Normal. Labs are within normal limits. Her GFR is probably around 75. Okay. I'd give her the option of her laparoscopic radical versus we'd do a robotic partial. The only thing that 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. It's not invading into the vein although it does have contact with the collecting system for sure. So there's trade-offs with both those procedures. She's gonna lose significant renal function by removal of the whole kidney. The partial on the other hand would be associated with somewhat higher complication risk. So what do you wanna do, doc? If she was, she left it up to me, I would do a partial. Okay, and you would do it robotically. Yeah. Dr. Chapin, any role for neo-adjuvant therapy here? Okay, that's distinct. How would you manage this patient? 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 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 gonna do a radical nephrectomy, you would do a biopsy to prove it. For a small mass, yes. If I'm gonna do a partial nephrectomy, there's no reason to do a biopsy because I know that the rest of the kidney is still gonna 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, sometimes the biopsy doesn't always say benign, benign. Sometimes it's inconclusive or uncosidic. 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, you know, 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 kind of buy that argument. What about the argument that if it's active, if we're gonna do active surveillance, we should do a biopsy, do you agree with that? I do, you know, 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 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? Yeah, show of 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 gonna show, we probably won't be doing anything. So unless a biopsy is gonna change something that I'm gonna 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 patient's leaving to us to decide or to help them decide, I would not do the biopsy unless it's gonna change what I do. Meaning if it's gonna 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. Patient, we've already decided we're gonna 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 gonna use the result of the biopsy to see if I'm gonna do surveillance or not. So if I'm doing surveillance, what is a biopsy gonna tell me? If I know 100% I'm doing that. You know, I guess my, and 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, even for cases where we know it may not change the management, at that time period, I still encourage a biopsy. So Chris, I guess so then my esteemed urology colleagues helped me as a simple medical oncologist understand because we've, I've had your colleagues from Philadelphia, you know, say that they wanna 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's different. Is your data sets would be different? If you knew there was cancer there and you were still gonna 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 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 gonna be benign. And so the growth rate per year is predicting the likelihood of malignancy and that's a different mindset and if you knew it was cancer, you would want to monitoring it because if it was below a certain size, it wouldn't metastasize. So it would be too 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 carcinomas. 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. You might say, holy cow, we gotta do something. Exactly. You know, my practice, I typically don't biopsy patients on active surveillance. I, you know, sort of like I've already decided that I'm not gonna intervene so I'm not sure I really wanna 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. The Canadian Jewels Group is actually biopsy. So this is a 72 year old white male who presents with uncontrolled hypertension. He underwent abdominal imaging which revealed an asymptomatic renal mass. Fast medical history is significant for hypertension, peripheral vascular disease, disease with a stent in the left lower extremity. Physical exam is 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. Dr. Chapin, these are the films. Give us your thoughts about this and how would you manage this patient? So obviously there's a left renal mass. And that first image, are you showing us something different or is that medially, is that renal vein or is that nodal tissue? I'm not sure, doctor. I'm not gonna tell you. Yeah, a single image. It looks like it's potentially renal vein involvement. Chris, do you wanna show that for the patients? I will. I was hoping to get Dr. Chapin a consult first. Dr. Pram, 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. Looks like this is the, I know. Oh, 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 a filling defect here. And that's pretty much it. That's all we're seeing this part. So you have a locally advanced tumor with evidence of renal vein involvement. How are you going to counsel the patient? How are you gonna treat the patient? What are you gonna do? So I would do a metastatic workup first. Okay, we did that. That was negative. So in the setting of a renal vein involvement in the absence of metastases, I would offer him a left radical nephrectomy. Okay. So a couple of questions. Would you do it open or would you do it laparoscopic or would you break out the robot? Yeah, I mean, anything that's been involved, involvement with renal veins, I've been doing them open. I know Dr. Matin may have a different opinion. Would you do a lymph node dissection or a no lymph node dissection? In the absence of clinically apparent nodes, only just because you and I have different opinions on this in general, I would not necessarily do a lymph node dissection on this. If at the time I felt something was clinically apparent or enlarged 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 inter-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. Matin, how would you approach this patient? Yeah, I think open is fine. If that's what you're comfortable doing. I'm 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 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 venal vein involvement. It's much easier to do it on the right side for me at least. So I would do an open nephrectomy and then do at least the lymph nodes on the aorta on the left side. Okay, would anyone consider this patient for a neo-adjuvant trial? If there is one available, yes. Okay. So patient undergo surgery and it's clear cell, grade three. Obviously T3ase is involving the renal vein. 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 six week followup imaging and I know that that sounds aggressive to some, but CT abdomen, chest abdomen and pelvis actually, it's six weeks to see if anything is apparent and also the set of baseline for comparison. And then I would 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, and Dr. Matin, how would you follow this patient? Very similarly, either every three months or four months depending on some other factors. 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? What would you do with the adrenal? What would you do? I think it's one of those, honestly, you're damned if you do and you're damned if you don't. 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 of 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 three years later. So 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 micrometastatic disease in there. And for all of you out there, if the adrenal looks normal on CT scan and the cancer's 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. Right, and particularly I found, especially on the left side where the adrenal vein drains into the renal vein and you have a tumor thrombus that can be quite challenging to try and spare the adrenals. Yeah, that's a good point, yeah. It's been a strain. That would come out in this case. Yeah, good point. So can I ask, I've done it on clients whether one you should have, one you should do with an electomy, with an ephrectomy, and one you don't have to? So the, I mean, not formal guidelines to my knowledge, but I mean basically 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 you make an interpretive assessment at the time of surgery. Even if it's an upper pole kidney mass. Even if it's an upper pole 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 in this case, would you consider to remove the adrenal glands, or at least look for whether there is any adrenal glands in movement with the uncontrolled hypertension? On the left side? Yep. Yeah, I mean while we took it out. I mean they did do a field workup, so the point is that sometimes tumors of the adrenal glands, such as something called a pheochromocytoma, can be a source of 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 an important thing to do before surgery because you don't want the patient to have a hypertensive crisis in the middle of surgery. Okay, 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 of 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 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 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 here there's a nodule here. So small volume, potential lung metastases, they're sort of still in determinant at this point. Dr. Taneer, this patient presents to you. What are you gonna do? Biopsy, the renal mass. And the biopsy is done to tell you what? What cup of renal sarcacinoma he has. Right, and why is that important to you? Because it might guide the therapy. If it is a clear cell, has a different therapeutic implications, different prognosis. If it is not clear cell, the same way. So I think 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 have a hard time recovering and it becomes this race between 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. Dr. Hudson, what are your thoughts about this patient? I generally agree with that. I think that I would see this is 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 on this. The things that would lead you wanting to be aggressive would be the age of the patient 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% or greater of the tumor volume in the patient. So I think knowing the symptoms the patient's having coming in the door would be useful. Knowing if you could, how rapidly things were progressing would help you. 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 a clear indication not to proceed with cytoreductive surgery. So I hear and understand the concerns about the liver metastases. It's a real life case, real life patient, and it's a tough decision to make. 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 with all things being said, if you told me the patient had was completely asymptomatic and was and wanted to be aggressive, I would lean towards cytoreductive surgery if the patient was having any degree of hypercalcemia or any type of poor risk factor on the traditional hang criteria. I would lean against that and would proceed forward with targeted therapy. And what would that targeted therapy be? Either a votrian or a sous-tent. Dr. Taneer, you never mentioned what therapy you'd give. Ideally, participation in a clinical trial. But I think either one of these two are acceptable. Okay. Dr. Karam, what are your thoughts? So I wanted to ask Dr. Taneer, would this patient be or would you not send him for consideration for surgery until you have biopsy-proven liver meds or are we gonna 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. No, I think if you have a good CT or an MRI and these clearly you can tell that these are not hemangiomas but rather liver metastasis. I don't think it is necessarily there's really a need to do a liver biopsy. Now, if you are not sure about liver metastas or not then I think you could do a biopsy of one of those liver lesions instead of biopsy in the kidney, biopsy deliver and if then it is definitely metastatic then you have the answer. But I agree, I think we need to get more data about the other parameters that we take into consideration to categorize the risk of this patient in terms of this good risk, intermediate risk or favorable risk. What would those be? 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. They're all normal. Okay. So he has an intermediate risk disease by virtue of presenting with advanced disease and so that's one risk factor and then he has, didn't you say anemia? Wasn't he, or the hemoglobin is okay? Hemoglobin is okay. How bad is this growth hematuria? I mean, I think that's also an important factor to consider if the bulk of the tumor and this patient is in that kidney and looks like from the scans, more than 95% of the tumor in this patient's body is in the kidney and the patient's having severe, maybe severe bleeding. Yeah, one episode of growth hematuria 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. Yeah, it's hard for me to buy not wanting to do cytoreductrin to affect me for small volume liver disease and I see the point that if you have more substantial liver disease but those are very tiny and it's just, again, I don't have your experience and I know we're all kind of creatures of where we trained in our experience so if you have experience in-house of you tend to pattern your treatment course for that but understand as patients that this is a gray area that when to do cytoreductrin to affect me, we don't want to offer that type of procedure to patients who aren't gonna do well with 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 cytoreductrin to affect me, upfront cytoreductrin to affect me and who would not? Good, so we're all in agreement. Excellent. No, I want to comment, this patient is only 49. He has lots of tumors in the body. He has good performance status. If you, theoretically, if you remove a large burden of tumor from the patient's body, he might do well. I know the data show that patients with liver metastasis will not do very well but considering his age, considering he's doing really well, considering this physiology, I would give it a try if my surgeon colleagues agree with me, so. I think it's not 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 certain trial is the timing of the nephrectomy is it upfront or is it delayed? And I think somebody with liver metastasis, whether large or small, I mean, if there are multiple, I would be concerned about the possibility of this patient having rapidly progressive disease posted up six weeks later to allow healing. Unless the patient is having refractory, continuous, gross hematuria 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 if you 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 gonna treat the patient with upfront, then that's an argument for doing upfront certain nephrectomy is to send the patient for high dose R2. You know, 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. You know, the other thing we know is that when 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 criteria that actually you developed with Steve Culp and what Chris did here was they identified six factors that if you had basically more than three of them, if you had more than three of them, then 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. The liver and anemia wasn't in the list, right? Yeah, so those factors were lymph nodes in the abdomen, lymph nodes in the chest, several blood markers that were high. What else was it, Chris? LDH and alfabas. And liver disease. 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 side or reductive surgery for someone with liver mets, but they are very small and it's a young patient who's gonna 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 Dr. Tenir waxed philosophically about why he would not send this patient for side or reductive nephrectomy. It's actually his patient and he sent him to me for side or reductive nephrectomy. But the goal was to enroll him in the ADAPT trial, which you've heard about earlier today. The ADAPT trial is a trial where patients are randomized to receive a personalized dendritic cell vaccine, basically their tremors process to make a vaccine 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 side or reductive nephrectomy in the presence of liver metastases and offer him this. So we took him to surgery, we did the left side or reductive nephrectomy and also biopsy, one of the nodules in the liver did turn out to be positive for metastatic disease. His final stage was T3A N0M1, Berman's grade threes, that 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 side or reductive 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 would recommend continue to follow. His lung disease really hasn't changed dramatically. There's the same small spots, there's the 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 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 he's- So you wouldn't change that recommendation, you would keep him on the trial? I mean, it depends, did he develop also now hypercalcemia, high serum, elevation of his high serum at the age? No. So I think we already enrolled him on the trial, that was the motivation to break the rule and do the upfront diffraction because we have an 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, to produce the vaccine, to allow the patient to get sunatina plus vaccine. So that was the reason we broke the rule here. So I think if, unless the performance status declines precipitously, unless he's developing neporous features with high serum LDH, high serum calcium, high platelets, high white blood cell count, if he did not develop these poor prognosis factors, then I think proceeding with sunatina plus the RNA vaccine. All right, Tom, you don't have this trial at your center, what would you offer? That trial is a great trial. We just didn't participate because of logistical reasons with the urology department, but that trial is great because you're not denying patients an active drug, which is currently the standard. So synidinib, there's nothing proven better than that agent at shrinking the tumor. And so 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, they would most likely either get synidinib or votrant, that's a standard. Okay, Brian, you look like you wanna say something. I'm just gonna comment just to make sure that people are aware of the, you know, in a 49 year old where 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 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 wound complication or a fascial dehiscence or was delayed therapy by months before while those liver meds progressed. So, you know, we obviously are taking all that into account when we're thinking about these things, but I mean, I think it's really important that we impress upon the importance of looking at kind of the risk of the surgery itself and whether or not these patients are gonna 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 side-reductive surgery. I would have offered him systemic therapy up front with possible delayed side-reductive 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 I would see that it would have. Yeah, we're definitely right. Don't worry. It wouldn't have. All right, let's do one more case and then we'll break, we'll, let you go out and get the lunches and bring them back in here and we'll continue on with the case presentations while we eat lunch. So, 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 nephrectomy. 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 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 colectomy for his ulcerative colitis. He's had a left partial nephrectomy, a left radical nephrectomy, a right adrenalectomy. He's had lung surgery in the past for a benign tumor. And he's had a TURP or resection of the prostate. You can 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 scans could not be done with contrast. They had to be done without contrast. 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 adrenalectomy. 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 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, in patients who've had retroperitone or recurrences who undergo re-resection, there is a real mortality risk. Dying of the operation itself or dying while in the hospital. 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 seem 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 seek consultation from you. You're killing me. And I would, I'm not in the hospital. I'm traveling. So you're on your own. What are you gonna do? You know, 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 go for it, you tend to be heroic here and try to go for it. But, I'd be very hesitant. This disease 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 I would do a midline approach to resect his left fossa recurrence and his right adrenal recurrence or adrenal fossa recurrence. Okay, and he would not have any adrenal glands left. So what are the implications of that? He'd have to be on replacement therapy. Which is? Mineral corticoid and the gluteal corticoid. So prednisone in Florida for the rest of his life. Yeah, what's left of it? Dr. Karam, Dr. Chapin's office next to yours. 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, just what, Dr. So, if the first thing to do is to make sure that, to do a complete metastatic workup, 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 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. Define healthy enough because he's got renal insufficiency to the point that he can't get contrast for CTA and he's got a history of hypertension and had multiple abdominal surgeries. But that's... Is 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 look for you to see. Sorry, I didn't know that was going to pop up. One thing to point out about his disease kinetics is 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 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 sort of sputtering along over the course of six, seven years and now with the course of one year, it did more than it did the previous six. Okay, so what would you do? I'd actually would call Nizar because 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 that does not negate anything that Dr. Karim said. His real chance is surgery. But the fact is, the likelihood is, is that he would recur pretty quickly afterward. But I would still explore all possibilities with Nizar. So as it turns out, he has fairly significant renal insufficiency with a GFR of 27. He is anemic, his 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 Dr. Tenir, 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, all these good therapies that we have, unfortunately, they're not established or they have not been demonstrated to be effective in the non-cliosal histology, especially papillary type two. Papillary type two, in my opinion, my experience, is one of the toughest ones to treat. There have been retrospective studies. We did a single-arm phase two trial in non-cliosal and we had 27 patients with papillary RCC. We treated with synitinib on that phase two trial and the results were not impressive at all. In fact, of the 27 patients with papillary treated with synitinib, zero responded, and the median progression-free survival was 1.6 months. We published this in 2012 in European Urology. Now, some of these patients maybe were like him with comorbid illnesses. Some may have had performance tests of two, but these drugs that we discussed this morning don't really produce the results that we see with clear cells. So I would try to convince the patient and convince the surgeon to go and do surgery. Now, if he's adamant against having surgery- If he's adamant. Then we will try. Try what? Try synitinib, you know. So synitinib would be your first choice? Well, I will try to see if his insurance would cover off-label drugs. It's independently wealthy. You can cover it by whatever. So why don't you tell us what you would choose? Well, I think the drug that Tom mentioned this morning, comatric or kabuzantinib would be a drug that I would consider. Tarsiva erlotinib has been shown to have some activity in- He wants to know what Dr. Taneer would recommend. I would recommend if his insurance would cover kabuzantinib, then we'll get him kabuzantinib. Okay, and if he's indigent, what would you recommend then? Then, you know, again, if he's not gonna be able to get erlotinib or kabuzantinib, then what did you tell us about his performance status as well? Performance status is one. Yeah, I mean, then you can try synitinib and tell him that the results are not 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, in our group, it would be the phase one group or the molecular markers group. And, 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 trial. JJ, you and I have done a couple of cases like this. What's that? I totally agree with you. However, phase one, we are declining him upfront because his kidney function is low. So, but even in that case, you can still do the exome sequencing. His papillary type two, so it's possible that he has CMAT mutation. And if that's the case, just like what Dr. Taneer said, we can try cup of zanthonyl, which is a CMAT inhibitor. So, if you can match the mutation with the drug and the likelihood for success can be up to, you know, 70%, so. Okay, so your choice would be carbazantinib, if you can get it, otherwise. Otherwise, I mean, you can try one of the TKI's. You know. Yeah, what one do you want to try? I would agree with Dr. Taneer. Try synanthonyl upfront. Okay, Tom, any different thoughts? No, all of the above. I tend to use nexivar a lot for my non-traditional histologies that don't fit any other pigeonhole for anything and with anecdotal evidence of some people do well for long periods of time. And one strategy in this guy who's not going to do well, he has a lot of negative features upfront with his disease, his past medical history, his borderline renal insufficiency. I mean, he's at two point GFR of 27. For you all in the room, the normal should be in the 60 to 70 range 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 stratify is if you put him on an agent and he was had a period of stable disease, that you could contemplate some type of resection later. Because at least you know that his, he wasn't exploding. Because it seems like my experience has been whenever we've taken patients from multiple metastectomies, that one of the biggest concerns is it just pops right up again and it's spreading while you're recovering. And so if you could, if he was able to demonstrate control on a targeted therapy, although that may be rare and not common, maybe one in five, but if he declared himself that way, then he may have a chance with being more aggressive surgically. Okay. Thankfully his disease hasn't progressed while you guys have been babbling on up here. He was initially treated with synitinib, stable disease progression at five months. Changed to Everlimus, stable disease. Significant toxicity noted with both the synitinib as well as the Everlimus. What do you think? 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. It was actually invading into the gallbladder so you had an unblocked cholecystectomy and also partial hepatectomy. This was done in April of 2011. You can see the pathology. Thankfully he had a good surgeon so he recovered nicely from surgery and did well until October of 2013. He then showed up on staging evaluation to have a paraaortic renal fossa recurrence with CT chest and bone scan that were negative. His cratin is, kidney function's even worse with a GFR of 23, cratinine of 3.19, although he's no- Would you get any 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. So, well, okay, let's ask him. Dr. Tenere, would you have given this guy- Tom says no. 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 here's his films, and you can see, and I'll show the audience here, he's got this one little area of recurrence right here, right next to the aorta. His kidney function's even worse, and he has an even more hostile abdomen because of his previous multiple surgeries. So, again, brief, please. Dr., let's see, Dr. Matin, what would you do? Well, he had a reasonable response to the first couple of agents, and so I would, again, call Tom or Nizar 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 the suffering, but... The suffering of what? Treatment. Are you doing surgery, or? 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. Matin 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 bowel right here? Sorry, I'm sitting on top of it. Well, I 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. 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 is what the other two said. I mean, essentially, systemic, they put it 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 oncology, anybody in medical oncology want to do surgery? I think the same is surgery for today, so. I'm sorry to say that again. I think the same is surgery today, so. You would offer surgery? Well, at least some local intervention if it's possible. I don't know if you repeat those target agents, whether the tumor apparently didn't respond. It became refractory. If you treat, I don't 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 therapies 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. We also took out some of the lymph nodes and 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 additional systemic therapy, we know what this thing is. It's not gonna shrink it. It's not gonna make it go away. It's gonna make him feel terrible and probably make him a worse surgical candidate. So I thought that aggressive local resection was probably the best way to go. So one of the things we're remiss about, it's my fault that 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 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 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'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. Did you have a question? Anyone? If not, we'll proceed with some more cases. And 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. LFTs 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 gonna do? Right in the frectomy 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 from the, 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, presuming you're allowed to do this. What would be your approach? Yeah, so in conjunction with you, Dr. Karam or Dr. Mateen, I would perform a right radical in the frectomy 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 gonna 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 a tumor. Any, would anyone consider it? No. 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 the 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 compromise 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 this syndrome. It's 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 in 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% 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. Yes, that's an aggressive subtype of kidney cancer and you hear in this situation it's 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 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 a high grade tumor so that this patient is at a very high risk of recurrence in the future which goes down to your question there how often would you follow the patient how would you treat them? 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% 50% risk of recurrence? At least Dr. Matin, you agree with that? Yes, perfectly Anybody else have any differing opinion? Rabdoid 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 for cervical cancer which was treated with a cone biopsy and she had a CT chest and an MRI of the brain that was negative 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 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. Dr. Gao this patient shows up in your clinic what are you going to tell him? I think first of all you want to make sure the diagnosis so she has a history of cervical cancer I assume that's you know that's a early stage but still is two sides of disease so you want to I would biopsy of that sacrum mass so you would biopsy of the sacral mass or mass okay Dr. Dr. Karam do you agree with that approach? yes so you would biopsy of the sacrum mass? yes Dr. Tanir is that your patient what did you do? 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 hot spot right here is 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 different from that? I would just we definitely want to biopsy the sacrum mass over the kidney primarily that would be my choice yeah the problem nobody actually did you didn't do a biopsy she was presumed that this represented metastasis and I guess on you know cervical cancer metastasizing to bone and as well as to the kidney I think but I'm not even like I'm less concerned about the cervix since it was treated with a comb biopsy but I would be more concerned about something else like like another primary like primary bone sarcoma or osteo bone sarcoma metastasizing to the kidney? no I think there 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 or if it's a sarcoma and the patient needs good kidney function for chemotherapy for sarcoma then I would treat the sarcoma with chemo first and then do the nephrectomy at a later time but the chance of this being another primary it's always yes in differential diagnosis that's you know practically practically speaking this is very unlikely to be anything else but renal cell with metastatic sacrum I mean this is a pattern of behavior of RCC it's unlikely we've seen I mean we've seen we had patients together where the patient has multiple lymph node enlargement up and down you know from chest all the way to the pelvis and has renal mass yes there you would biopsy 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 learned 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 under what is said reductive nephrectomy 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 balloon we have a question Jose and I have a question to ask you would you have considered doing a partial nephrectomy in that patient that was what I was going to ask you actually so yes I would have that's why I'm asking going back so Dr. Karam believe you're you have published or a beginning or just now publishing the role of partial nephrectomy and metastatic disease what is the role of partial nephrectomy in the setting of metastatic disease? the publication that we just have is a small number of patients over a long you know duration it's about 33 patients but the bottom line is whenever it's technically feasible to do a partial nephrectomy that's not a heroic type of partial nephrectomy and this is a feasible partial nephrectomy we should consider it especially if the patient has you know borderline kidney function okay so this patient doesn't have borderline kidney function she has normal contralateral kidney yeah you know I agree with you you could do a partial nephrectomy 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 robot yeah no you would not yeah I know you you would not having having said that when we talk to the patient with a metastatic disease about a partial nephrectomy we have to be very careful and tell them that there is a higher risk of complications with partial nephrectomies so that might delay their you know 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 you know a large mass invading into other things I would definitely not do a partial but for things that are doable I think we should at least entertain the idea my approach were 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 you know 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 appropriate to show that the lymph nodes are negative if your plan is to treat that metastasis possible with a resection later on by metastasectomy is that do you think that that metastasis is receptable no I don't seem to think it is at this point but you could also treat you could treat it locally the point is in the absence of other metastatic sites I think a lymph node dissection may provide some information here okay and then the patient develops callous societies and has a drain sure there's risks with everything I I'm actually amazed she had a radical would have absolutely done a partial would have done a robotic 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 but 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 yeah and I 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 okay I mean I would agree that if it's that's pretty clear cut that that's separate I mean I think that that would be on the lower end of 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 node dissection in this patient with metastatic disease to bone in the 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 RPL&D 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 57 year old 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 one, she has a past history of miastinia gravis, gastroesophageal reflex disease and also ADHD, she's had a C-section and had a thymectomy, C-section times three in my thymectomy in the past for her miastinia gravis and here's a locally advanced tumor involving the right kidney with an IVC 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. So there's no metastatic disease, what do you mean she has poor risk disease? Yeah, I mean just the poor risk features with with the other lab studies but I think surgery would be her best option here with an ephrectomy and thrombectomy. Okay and would you would you do another dissection? Oh yeah, I mean for thrombectomies it would be part of the procedure to free up the vessels so we would do a lymphoma dissection as part of the operation for all the IVC or most of the IVC thrombi. Is her lower extremity edema because of compression or probably been a cave IVC syndrome or does she have also hypoalbuminemia? Do we know her serum albumin? Serum albumin is normal. Okay. So yeah the lower extremity edema is just related to back pressure from the IVC thrombus. So she underwent an erratical nephrectomy and she had 90 greater than 95% sarcomatoid slash rhabdoid de-differentiation. The tumor was invading into the renal vein and also into the arterial wall and was present at the margin of resection. 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 distant 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 you know we don't see arterial margins you know uncommonly at all on 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 Jeff right. Medical oncologist any role for systemic therapy here in this setting? Not of protocol and if he is not a candidate for a trial because of the positive surgical margin then we will offer we will follow her as mentioned you know six weeks or you know three months post-op with scans and then you know 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. Koran 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'll probably come back at the renal fossa, the lymph nodes, the liver and the lung among other places. I mean this is a very aggressive tumor and unfortunately it comes back quickly typically within the first six months. Aren't you optimistic? Okay Dr. Chapin? Yeah I mean I think it's inevitable that there's there's going to be a recurrence when you see sarcomatoid like like Dr. Karam says I mean I knew you presented some of that data today right but I think it's pretty much when? Well the tumor is already inside her body right the surgical margin is positive so it's basically 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 no evidence of recurrent 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 past medical 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 localized renal mass involving the anterior aspect of her right kidney. So briefly let's go down the line. Dr. Teneir what would you recommend for this patient? So she has no metastatic disease. No metastatic disease. This is a small SRM small renal mass. Right and a 78 year old with so many meters. 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. Mateen's surveillance trial. I hope it does not mandate a biopsy but if it mandates biopsy will do the biopsy but I would definitely offer a surveillance. Okay Dr. Gao briefly what are you going to do? Yeah I would agree. I would send the patient directly to Dr. Mateen. Okay would you do a biopsy or no? You know with with her age and the comorbidities I would not. You would Dr. Chapin? Yeah biopsy and surveillance if the patient refused robotic partial. Wait a minute so you would you want to do a robotic partial? No no no no biopsy and surveillance would be my first choice. If the patient refused surveillance I would do a robotic partial. Okay and the surveillance would be regardless of what the biopsy shows? Yeah for the most part. I still agree because I agree with Dr. Mateen 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 three tumor maybe it would change my mind. If it came back as a benign maybe it would be less frequent imaging but I want to know what it was. Okay Dr. Kram. I would recommend surveillance without a biopsy and then without the biopsy part for two reasons. Number one she has atrial fibrillation is on anticoagulation so I don't want to take her off the anticoagulation 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 the time. Biopsy is good to tell us the histology you know 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. Mateen. Yeah you know 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 anticoagulation so that's not an issue but you know I think Brian makes a good point if he actually can show 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 an abdominal mass. It's palpable no urologic symptoms performance that is zero had an eight pound weight loss all labs within normal limits MRI the brain and bone scan are negative and 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. There's one before then yeah just the presentation oh okay weight loss okay I'm sorry go on. Okay 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 or ductive nephrectomy yes or no? Let's just go down the line Dr. Tenir? Yes. Dr. Gao? Dr. Yes and all three of us. Okay so no one would offer him pre-surgical therapy? Not off trial. Okay suppose you had a trial would you offer him that? Yeah. Okay so I'm gonna let you in on a little secret. The case is going to turn out very well because actually this patient that we're getting we're talking about right now is in this room. Okay so he's gonna have a good result regardless. He enrolled in the synidinib pre-surgical trial he had a biopsy of his lung lesion it revealed metastatic clear cell venous cell carcinoma and he was started on synidinib 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 half-cytodroductive 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 although there's still local extension into the 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 you know 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 them for the synoductive nephrectomy and then continue synidinib do you switch to the mTOR inhibitors either everlimus or temserilimus do you switch to exitinib or do you do the set of reductive nephrectomy and then change the TKI post-stop. Dr. Tenir quickly. I would proceed with the set of reductive nephrectomy and then restage him post-operative. I mean the protocol that was the the spirit of the protocol patients after two cycles of synidinib if they have stable disease or have responded will will proceed on having set of effective nephrectomy with restaging post-op if their disease is still stable or minor progression then they can continue with synidinib. Okay Dr. Gao. So yeah I would you know I initially I would not treat this patient because just because you know a small portion of patients after cytoreductive therapy actually have shrinkage of the metastases so if he is one of these patients you know 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. Dr. Chapin, Karam, 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 cytoreductive followed by reinitiation of synidinib. Anything anything different guys? Number two okay so overall assessment was there was slight progression of disease in the lung but the 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 metastases 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 buy the blood under an electrum? Yeah I'm reading that I'm actually holding on. Now we left that I did this with you I believe. We just did the mass. I think we left the left adrenal because the right adrenal mass because it says there's surgery left adrenal. No we just we just did it we did a partial adrenal. Yeah I think we left the adrenal tissue the mass and leave we left the adrenal tissue behind. Postoperatively 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 everlyness and as I say he currently is president this meeting so he must be doing 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 METS so Dr. Gao what would be your approach to this patient? You know of course you know we need to know the diagnosis of this patient first so what are you going to do? So sorry did he have METS to anywhere else? He has bilateral pulmonary nodules locally advanced right primary tumor and no other haven't some 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? I would biopsy the tumor the kidney tumor. You would biopsy the kidney tumor? Okay Dr. Tenir 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 associated negatively with survival the other thing is anemia so if you look at the at the case here you have a patient who has advanced disease with poor risk 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 the burden of his disease is in the kidney so in this patient I would proceed and take the kidney out I would do a psycho reductive 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 postoperatively 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 and if he it is clear cell 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 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 of the 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 yeah and he does not have brain mass that does not have multiple bone mass does not have liver mass 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 taping what are you going to do and I guess I would ask Dr. denier a question about his response and if if a biopsy were to show papillary or chromophobe would you still recommend the side of an effective 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 chromophobe 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 so more reason to do surgery yeah so I mean given that answer I typically would not biopsy this mass unless the person was eligible for a 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 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 diagnose it first right well I think on medullary I mean obviously it's 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 the sickle cell trait so I mean mostly in the acid are African-Americans Dr. Karam I would choose number three you would choose number three would you and you would not do a biopsy no be the ultimate biopsy okay Dr. Mateen anything different no okay patient under one side of reductive nephrectomy there's a pathology t3a n0 1 clear cell from his grade 4 and he shows up six weeks later with modest progression of their pulmonary metastases so Dr. Tenir high those are too as I said so you would offer the patient hydrocyl 2 that would be your upfront choice if again postoperatively the kidney function is good yeah Dr. down yeah you know you want to make sure all the organ functions okay lung function heart function kidney function if it's okay he's relatively young certainly you can talk to the patient about high dose IO2 what would be your recommendation though 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 high dose IO2 therapy even though the response rate is low but that's the only chance what is the response rate so the the overall response rate is is about over 20% so but the complete response rate is less than 7% partial response rate is about 15% so if if he can achieve complete response rate the chance for him to live up to 10 years will be about 80% but his chances of doing that are about six and 100 right that's right so it will be like 7% times 90% so that would be 5% to 6% Dr. Chapin your thoughts I mean after extensive counseling I would consider recommending IO2 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. Cron typically I would refer the patient to our colleagues from medical oncology but IL2 sounds like a reasonable approach and we can always give TKI's after IL2 and we can't really do do it the other way but 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 cutoff where you would be more nervous giving IL2? It is more important than chronological age is physiological age so if the patient is 70 and is fit then that's fine so there's no specific age cutoff then? Well obviously we don't give IL2 to people who are 75 and older I think the oldest patient I know has received IL2 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 three or four doses instead of you know the eight or nine 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 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 you know this all this objective studies if everything fits well together yeah you go ahead and do it. Dr. Mateen? Yeah I mean I you know the patient's gonna have to get 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 cytoreductive nephrectomy but it's actually one where we take patients with metastatic disease and actually ablate one of their metastases and then shortly thereafter follow it up with one of the agents that Dr. Gao 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 and again it is not yet 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 cytoreductive nephrectomy and then as long as they're doing well they actually continue getting the immunotherapy. So 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 our interventionalists feel like they can do and as you know they've gotten pretty talented and safe so they can do the lung fairly safely they have good experience with that they have tremendous experience with treating bone lesions they can do we can do soft tissue sites if there's a tumor in the other kidney we could always do that also as part of you know getting some local control and that 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 three of us 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 yeah yeah. So I always laugh about this in fact prior to 2006 when alls we had was interleukin 2 and the medical oncologist used to say all the alls 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 the case and you ask them okay what do you want to use they go interleukin 2 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 sir. Thank you Chris by the way. Oh my pleasure. You had a question? I've heard it mentioned about uh kidney cancer spreading to other organs invading other organs and like nodules in the lung how do you differentiate between this kidney cancer that is spread and lung cancer what's the difference between the two? Um well and I'll answer first and then let one of these guys chime in. 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 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 helps you make the decision as to whether or not it represents a primary tumor of the lung versus a metastasis from the kidney. Usually the lung cancer uh 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 spreads 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 uh on the CAT scan of his chest and I suspect this was a new cancer that rising in the lung so we biopsyed the lung and it was sure enough square mesococinoma of the lung that was just beginning in the right upper lobe and we treated it with radiation. So yes we need to be uh 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 the 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 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 than 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 can have melanoma that has spread to the kidney breast cancer was one of the the topics today that we were reason why some of us were looking to biopsy because we are concerned maybe the breast cancer had metastasized to the kidney it's still breast cancer that's now in the kidney it's not kidney cancer just because of its location but it's the origin is from is what we describe it from. So I just want to make a couple of comments so over 90% of the patients with lung cancer actually are smokers so you can just ask about the smoking history so that will give you another another clue. The second one to answer your question about regard about which type of cancer will be better so it really depends upon the stage of the 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 so. Okay again we can't thank you enough for coming we hope that you found this informative and somewhat entertaining.