 So, a 51-year-old comes with a left flank pain and blood in the urine, good performance status, slightly anemic, but otherwise, labs are within normal limits, CT chest is negative, and the patient is offered a laparoscopic radical nephrectomy. Here are the images. You can see a locally advanced tumor involving the left kidney. There's maybe some shoddy lymph nodes present here and here. No metastatic disease. Dr. Mateen, what are your thoughts? Yeah, I mean, I think that's fine. You know, the best answer is to basically do whatever you're most comfortable with in terms of giving the patient the best cancer outcome. If you have the experience laparoscopically to do that and as well sample those lymph nodes, then you should. If you're uncomfortable, then either refer them or do it open. And so what would you do? Oh, I'd do a laparoscopic nephrectomy and do an emphatomectomy. And when you do a laparoscopic lymph node dissection, are you able to get to the interurata cable nodes, which are the nodes between the aorta and the vena cava? Yeah, we can. Now, whether that actually makes a difference or not for a patient like this is still a question. And, you know, I would at the very least do the ones between the aorta and the kidney. You know, there's talk about doing a frozen section, seeing if there is a disease there and then doing more. Is that what you do? No. No, I don't. I mean, we could discuss it, but you know, I don't. And I'm not sure there's much benefit in going, you know, interurata cable if there's multiple nodes present. Dr. Cram, what are your thoughts? I would do a laparoscopic nephrectomy on the left side and then do the lymph nodes just between the aorta and the kidney. I wouldn't necessarily go between the aorta and the vena cava. Dr. Chapin? I'd probably take a little bit of a different approach and I would actually do a nephrectomy with an extended lymph node dissection to include the interurata cable nodes. Whether this could be done with a robotic assistance would make me more comfortable for doing interurata cable with a minimally invasive approach. So I would do a robotic nephrectomy and an extended node dissection to include the interurata cables. Robotically. Correct. So the patient elected to have their surgery at home in Tennessee and they underwent a laparoscopic radical nephrectomy. And the pathology, which was reviewed here, showed a renal cell carcinoma 6 centimeters in size, clear cell type with focal sarcomatoid features, 10 percent, firm and nuclear grade 4, invasive into the renal sinus soft tissue, margins of resection negative, adrenal gland negative. So this would be a T3A N0 M0, Perman's grade 4, clear cell, renal cell carcinoma with negative margins, 10 percent sarcomatoid. Is it N0 or NX? NX. Well, the nodes that were removed were negative. Dr. Tenir, the patient comes to you and follow up. What do you tell them? They're at risk of recurrence because, again, size, the more than 4 centimeters, firm and nuclear grade 4, 10 percent sarcomatoid features. And as you said, T3A, if there is any clinical trial that they're interested in and they're eligible for it, I would offer them adjuvant trial. So you'd offer them an adjuvant clinical trial? Okay. And if they're not eligible for the adjuvant trial, how often would you follow this patient? I would follow the patient with a scan three months after surgery and then another one six months later after that surgery. So every six months? Yeah. Twice a year. Everyone agree or everyone disagree? I would follow the patient a bit closer. Although the cutoff for sarcomatoid, Dr. Tenir mentioned the 20 percent is not an absolute cutoff. This patient is at a very high risk of recurrence. And I would just observe every three to four months for at least the first two years just because of their high risk of recurrence. And like Dr. Tenir said, if the patient is eligible for a clinical trial, he should undergo or at least consider an adjuvant clinical trial. So the patient is observed postoperatively and he's told to come back six months for repeat imaging. He's asymptomatic. His CT chest remains negative. And he comes back with this. You can see he's got a rather large tumor involving his right kidney that extends really right up into the renal sinus and the renal hyalum. Two views. I trust these are adequate for you, Dr. Delacroix. Yes. Okay. Is that a positive lymph on the left? Yes. Where? Pariotic. Pariotic. On the right picture? No, that's cruise. That's cruise in the bow. So if you go back and look, there was a question of a hint of something sitting right here. I didn't want to point it out to you. Right there. And that was the genesis of this. So this would have supported doing closer follow-up. Dr. Latine, what do you think? So this came back and this grew this much in what, six months? One year? Six months. Wow. Yeah. Pretty aggressive. You know, I'd make sure he had recent restaging studies. They're all negative. And book them for a partial. Book them for a partial. Open. Yeah. And the likelihood of success? You know, again, I take the Delacro approach and ask for more images first. But assuming this is the worst that it is here, I think chances of success of actually removing the whole tumor and preserving the kidney at, say, greater than 90%, there would be risk of, what's that? 90%? Yeah. I think that's... Yeah. It's difficult. No question. Optimistic. Yeah. The whole kidney and, you know, I think we would give it the best shot we had to preserve the kidney and as well get the whole tumor out. Now, the alternative would be the clinical trial. You know, if there is one available in terms of treating the patient ahead of time in the hopes of getting that to shrink down. Dr. Karan, what are your thoughts? I think clinical trial will be my number one choice. I think this will be a quite a difficult partial nephrectomy. If the patient is willing to take the risk, then I would go for surgery. By saying risk, I mean the risk of ending with radical nephrectomy possibly. And what is that risk? I would quote the risk being higher than what Dr. Matins said. I would say, for me, I would say at least 50-50. But again, it still depends on the surgeon comfort and experience. But I would quote the patient 50-50 chance. Would he qualify for a new Edwin trial having had a previous cancer, even though it was treated? No. No. Dr. Delacroix, comes to New Orleans. Yeah, if I was seeing him in New Orleans, if he didn't qualify for a new Edwin trial, then I'd do an open partial on him. If he would qualify for a trial and be willing to travel, I'd tell him to get in his car and come see you for a trial. So that would be an easy one. What would I quote him? Numbers are, we try to objectify the, something that's not quantifiable. But I'd say 50-50. Yeah, I would definitely counsel the patient on the good possibility to wake up without a kidney in on dialysis. And I think this is important for the audience to see. So all of these guys either work together now or at least trained by the same people. And you can see that the variation in the, in their responses with regards to predicted risk of losing that kidney and so forth. So I personally thought when I saw this guy that he was going to lose his kidney, because, I mean, this right here, this tumor goes right up to where the vessels are entering into the renal sinus. And I thought that the likelihood of either leaving cancer behind to try and save the kidney or leaving it with no functional renal tissue were quite high. And so I said basically, your options are you could undergo a radical nephrectomy, go on dialysis, the possibility of a transplant two or three years down the line if you remain disease free. Or we could try targeted agents to see if we could get the tumor to shrink. So the patient underwent a biopsy. It showed high grade, clear cell, renal cell carcinoma. And he was offered nephrectomy versus pazopinib. Because the clinical trial, he's not eligible for a clinical trial with excitin. He decided to choose pazopinib. And he came, comes back 50 days after treatment with a CT chest that remains negative. And there are the films. And I would argue slightly bit easier to do a partial nephrectomy in that case. You can see the tumor here has shrunk dramatically. It's pulled itself out of the renal sinus and is much more amenable to partial nephrectomy from my perspective. You only want to write partial nephrectomy and it was a T1A, N0, M0, Herman's Grade 4 with extensive necrosis. So dramatic response. And, you know, again, admittedly this is an anecdote and you could maybe take 10 people and the other nine might not respond at all. But I felt that this was this guy's best hope at trying to save his kidney. Was that the newest TKI available at the time? No, excitin was available. So why did you choose that over, excitin had given your experience with excitin? I take that back. Excitin was available through a clinical trial mechanism, but it was not FDA approved. Right. Sorry. And had it occurred now, you would choose excitin based on your experience? For sure. For sure. Questions? No questions? Yeah. And I'm just going to ask, in the future, for future questions, please use the microphone so they can hear you on the YouTube broadcast, but I'll restate what you ask. Basically, you're saying why not just do the nephrectomy and then get a kidney transplant? Or just end up on dialysis? Sure. And well, in this case, if we had done an nephrectomy, he would have been on dialysis. The problem with transplant is in patients with cancer, they are not eligible for transplant unless they're disease free for at least two and some say three years, because the immunosuppression associated with transplant, if they had cancer, would let the cancer go berserk. And, you know, dialysis is not a cakewalk. I mean, having to go to a place for three or four hours, three times a week, and the mortality rate associated with dialysis is 10% per year. So that means that 50% of people are dead on dialysis at five years. So that's not exactly, you know, a good outcome either. I know this is a difficult question. How much work is being done right now on COS? We're talking about treatment here. I mean, that's the focus of this. I understand that. The question becomes, this individual had at once, was there any way of making a determination as to potential causes to help them avoid a recurrence or in some way looking at either environmental or genetic factors that might contribute to this and trying to treat that in the interim? I'll let Dr. Karam field that one. So as far as COS, I'm not aware of much research being actively done to look for a COS. We know there are some known risk factors. I think smoking is the one that most people would agree on. It's a very high risk factor for kidney cancer. There are other causes that are not as certain. I think they're more speculative, such as diabetes or high blood pressure or obesity as potential causes, but the link is not very strong. So we can't tell the patient if you lose weight, you will have less chance of kidney cancer. So these are associations. The main risk factor that we know of for sure are the genetic risk factors. So we know in about 5% of patients, genes play a major role. And this is something that would run in a family. But other than that, for kidney cancer itself, these are the main known risk factors. There are other cancers that happen in the kidney that are not labeled as kidney cancer that we know from environmental factors or from herbs and Dr. Matin might comment on that. But that's not kidney cancer itself. It's another subtype. Let me follow up because in my situation, I had a right in the front of me, my approximate cause was taking prozac. I had prozac. I became allergic to it, which caused vasculitis, which vasculitis is a known cause of renal cell tumors, especially if it goes into the kidney which one did. And it was very definite that the prozac caused the vasculitis because I was off of it. Vasculitis went away, went back on it and within 24 hours, the vasculitis was back full blown. And it was a short period of time after that that the renal cell carcinoma was discovered. And I had been clear before that because I had had some physicals done because of leaving the army. And I had no indication of renal cell carcinoma at the time. After that, and after my surgery and surviving it, I posted some stories out on the kidney cancer website and I received numerous, numerous responses back from all over the world. People with an exact similar situation. I know that no real study had been done as to the relationship between those or a direct relationship between prozac and kidney cancer but the steps that were associated were repeated multiple times, which is why I brought up the question. It's an interesting thought and like you said, there is no study that will be interesting to gather the data, but the risk with all these studies, even the studies that show that smoking is a risk factor is that there is a lot of confounding. So let's say if theoretically that drug A causes kidney cancer but all the patients who took drug A also are smokers, then which one is it really? Is it the drug A that caused it? Is it the smoking or is it the combination of both? And there are other cancers like drugs that cause them, for example, bladder cancer and a certain diabetes medication. But again, it's hard to tease out which factor because we live in a complex environment. It could be the medication, the water, the smoking or other risk factors but it will be interesting to gather objective data and see if that holds true when we account for the other known risk factors too. And interestingly actually alcohol provides a protective effect on cancer. Well that's good to know. Except that puts you at risk for oral and not cancer. He's joking obviously. In the 10 or so cases that you presented, it's sort of hard for us to tell by looking at that the size, sometimes you've mentioned what they are. But there's only been one, maybe two where neo-adjuvant therapy was considered something to do and I wanted to be sure I understood were you saying that's only available in a clinical trial setting or it was only a particular type of neo-adjuvant that was available only in a clinical setting. And then why that particular 50-year-old, this is where I was saying it's hard for us to differentiate that 50-year-old one before this one, was there something about that tumor characteristic or was it the age or something that led you to the neo-adjuvant whereas you separately is you've talked about robotic versus open versus laparoscopic and made different decisions along the way. Maybe there'd be just a primer as to what those are and why you'd use them. So with regards to the neo-adjuvant therapy, I would say that neo-adjuvant therapy in 2013 is still the subject of a clinical trial. It is not the standard of care. But in that other case that I showed, the 50-year-old that received Pizopinib, his choices were nephrectomy dialysis versus, hey, let's try this and see if it works kind of thing. So he was sort of between a rock and a hard place, but it was by no means the standard of care and that's the way he was informed, told that this is not the standard of care, that this tumor could actually grow while on therapy, but that in my hands at least I felt that he was almost certainly likely to end up with nephrectomy and end up on dialysis. And with that informed consent he decided to try the drug, but it's definitely not the standard of care. And then let's see, Dr. Mateen perhaps you'd like to discuss the differences or why we're choosing robot for this and lap for that and open for this. Okay. So to try to keep this short, open has been around the longest, right? And that's what we have the most amount of data with and that's probably the one procedure that you could translate in Houston, Chicago. I don't know why I'm picking on Sri Lanka today. It's just Saturday morning. I don't know. But in other words it's well accepted pretty much anywhere. Laparoscopic procedures came into Bikidware introduced in the 90s, weren't really accepted until early part of the century. But a little bit more difficult for people to pick up on. It just requires a little bit of a different skill set. And then with robotic technology coming into play that basically allows surgeons to do laparoscopic surgery, but it's done without having to relearn a whole new skill set. So it's still laparoscopic when we do it robotically. It's just that it makes it easier for the surgeon to do. Now there's a lot of other details I'm kind of leaving out. Bottom line really is it comes down to the experience of the surgeon, the training and their comfort level with what's being presented in front of them. So I don't know if that helps answer your questions, but it's not written in a book as to what you should do when because it's continuously evolving area with sort of these technologies that are coming out. And then the exposure that urologists have to them as they're in training or in practice. So I'll just add to that that the reason to push less invasive approaches is the recovery. I don't know if you want to say anything about it. Please, yeah. I think patients that have laparoscopic surgery recover much faster and more quickly than open surgery. How are you doing? In our case, our doctor doesn't seem to be real concerned with my wife's kidney. She's in stage four. And is that because it's already left the kidney and gone to different parts of the body? Well, we're going to talk more about that in the afternoon session with metastatic disease. But in general, we use selection criteria that have been published in the literature, some by us, some by others, to select patients for surgery. Not all patients who present with metastatic disease in their kidney in place are good candidates for surgery. And in fact, in many cases, the surgery can be quite detrimental. And it just depends upon certain selection criteria, such as, you know, in general, patients need to should have clear cell histology. They should have a good performance status, absence of brain, liver, and bone metastases. Those are criteria that we would use to better select patients for surgery. But our experience has been like, for instance, if a patient has liver metastases and you take them to surgery to take out their kidney, the overwhelming majority of those patients will be dead in six months. And it's directly related to the to the surgery itself because of the debilitating effects of the surgery and the ability of their metastatic disease to sort of take off after surgery. So we use very strict criteria to select patients for surgery.