 Good morning everyone. It's a pleasure to be here and thank you for coming out on Saturday morning to talk about kidney cancer. Scott and Fuki gave a lot of information about kidney cancer and epidemiology of kidney cancer. A couple of things that I just wanted to highlight in addition is that there has been a marked rise in the incidence of kidney cancer really since the early 1990s. There are a lot of hypothesized reasons for this and one of them is that a lot of kidney cancers are detected incidentally so it's not that you had some direct symptoms of a kidney cancer but it's found on evaluation for another diagnosis and these days you can't walk into an emergency room and walk out without a CAT scan and so the overwhelming majority of my patients with kidney cancer it was found because of some unrelated reason like appendicitis or a cough, something other than a direct symptom from their kidney cancer. Even though the rate of kidney cancer is on the rise, the rate of presentation with metastatic kidney cancer has been relatively stable as has the death rate from kidney cancer and that's something to pay attention to. Scott mentioned this as well and that's the staging of kidney cancer and when you look at stages 1, 2 and 3 these are largely surgical kidney cancers and when you look at stage 4, there is a role for kidney cancer in this population as well and we're going to talk about that today. When we think about stage 1 kidney cancer, these are cancers that are confined to the kidney but that are what we call small and small is all relative. What I consider small to a patient, you know, a 4 centimeters mass doesn't seem so small but in our sort of lexicon that's a small kidney mass. Stage 2 kidney cancer is bigger. It's still confined to the kidney but it's bigger. These are softball size tumors and when it invades the fat around the kidney or the vein draining the kidney, these are our stage 3 cancers and stage 4 is when it spreads to other parts of the body. Now this is now sort of an old slide but it's still sort of the best data we have showing the rising incidence of kidney cancer and because that rising incidence has mostly been because of new diagnosis of smaller kidney tumors, there's also been a rise in use of surgery for kidney cancer. So we're seeing higher surgical rates for kidney cancer than we were 10, 15, 20 years ago with stable to slight increases in mortality from kidney cancer which are a little difficult to explain and we'll talk about that in a second. And what's interesting about kidney cancer is that kidney cancer really comes in all shapes and sizes. We always say kidney cancer is very heterogeneous. So two people with kidney cancer may have very different kidney cancer behaviors. What we really like is we like everyone with kidney cancer to have a history of kidney cancer but that's not always possible. Some people have very angry, very aggressive kidney cancers and this is a very large kidney cancer that's actually invading the wall of the back. Other people have kidney cancers that are so aggressive that they're spreading into the vein, draining the kidney and going all the way up and into the heart. Some people have large kidney cancers but they're localized to the kidney and you can see sort of a clear black plane all the way around the kidney. And then sometimes we see small kidney tumors. Now this is a small kidney tumor but it's very centrally located in the middle of the kidney and this is an even smaller kidney tumor that's just sort of hanging off the outside of the kidney. And so truly an incredibly heterogeneous disease, kidney cancer. So I want to talk a little bit about localized kidney cancer. These are cancers that are confined to the kidney without any evidence of spread outside of the kidney and the role of partial nephrectomy and kidney cancer. Now partial nephrectomy is something that has been sort of critically evaluated now for about 20 years. Back in the 80s we only did partial nephrectomies for patients with imperative indications, meaning they only have one kidney or the two kidneys they have are barely enough to keep them off of dialysis. So even though they have a kidney tumor, we need to just take out the kidney tumor to preserve their health and quality of life. And that's a partial nephrectomy. Well it has kind of time and experience grew. We realized that we can do partial nephrectomies even in healthy people with normal kidney function to the point that today our guidelines suggest that everyone with a tumor that's less than four centimeters should get a partial nephrectomy. Yet still the priority is not saving kidney, the priority is cancer control. So it's kind of a priority when technically feasible. And so when the cancer characteristics mandate that it's okay to do a partial nephrectomy. Obviously if you're saving the bulk of the kidney, you're maximizing long-term kidney function. So if you take out a whole kidney versus if you take out part of the kidney, that person's going to have better kidney function. And because they have better kidney function, it's possible they have better cardiovascular health as well. In terms of cancer control, there was a huge clinical trial that was done in Europe in the 1990s that actually showed the opposite of what we would expect. It showed that patients that had their whole kidney removed did better than patients that had a partial nephrectomy. But there were a lot of problems with this study. Not just that it was done in Europe. But there were a lot of problems with this study. And so a colleague of mine from Michigan named David Miller and I did a study of what we call observational data. Data from a linked cancer network called CIR with Medicare claims data to try to understand with sort of the best available statistical method if this was really true in a contemporary U.S. cohort. And what we found was that there was a survival benefit to partial nephrectomy in yellow over a removal of the whole kidney in blue for patients with small kidney tumors. And if that benefit is because you're saving kidney and you're preventing the onset of cardiovascular disease that might be associated with it, you would expect that benefit to grow with time and it did. So there was a small benefit at two years that was larger at five years and even larger still at eight years. And at five years and eight years that benefit was clinically significant. And this is sort of the number needed to treat. And what that means is the number of patients in whom you do a partial nephrectomy instead of a radical nephrectomy to save one life. And at eight years if you do a partial nephrectomy instead of a radical nephrectomy in seven patients you're saving one life which is a huge number. So how is that applicable to 2016? Well it's applicable in that if partial nephrectomy is important how can we make sure that more patients have access to it and how can we make it sort of more technically feasible? And one of the ways that we can make it more technically feasible is with robotic surgery. So what's the difference between robotic surgery and laparoscopic surgery? They both use small incisions. So incisions that are the size of my pinky or the size of my thumb. But with laparoscopic surgery you have four degrees of freedom. So you can turn your instruments and you can move them left and right. But with robotic surgery you have wrist-like motion. And so if you have sort of a spherical tumor and you're trying to cut it out with those four degrees of freedom it's a lot easier if you have wrist-like motion to dissect around the tumor and to sew up the kidney. Laparoscopic partial nephrectomy is a very hard surgery. I used to do it. But that wrist-like motion really makes things technically a lot more feasible. The other thing that we think about is when I do an open partial nephrectomy I try to just squeeze the kidney and not interrupt the blood flow to the whole kidney if I can. But now robotically we can do some what we call selective ischemia techniques. So instead of interrupting the blood flow to the whole kidney we just interrupt the blood flow to the part around the tumor and the rest of the kidney gets to get good blood flow while we're doing the surgery. Now how does that influence the role of partial nephrectomy nationally? So we know that even as recently as 2005 to 2008 not enough patients were getting partial nephrectomies for small kidney tumors. But it seems that when people adopt robotic technology it's associated with a big increase here 30% in use of partial nephrectomy as a technique. And if you look at a more kind of recent time frame the patients that adopt or the providers that adopted the robot in the early 2000s had a markedly increased use in partial nephrectomy. But even recent adopters people that got a robot in 2005 to 2008 had a big increase in the relative use of partial versus radical nephrectomy. So how can we make partial nephrectomy less injurious, less damaging to the kidney? Well one of the ways is what we call selective ischemia. This idea of just pinching off the kidney around the tumor. And this is something called the Simone pole clamp. And what it does is it kind of that huge jaw right here it wraps around the kidney and then it clamps down and pinches off the kidney. So what you see and I actually now that I think about I should have had a picture of this because I had a really cool picture where you see pink healthy kidney to the left and white kidney to the right showing you how it pinches off the blood flow just to the area where the tumor is. And unfortunately to do that you have to have a less complex tumor right if a tumor is right in the middle of the kidney you can't pinch off anything. So that tumor necessarily has to be sort of hanging off the upper or lower part of the kidney. And what we found in our experience and we actually have the biggest experience in the world in using this clamp. But we found that it didn't affect blood loss so you would imagine that if you're interrupting the blood flow to the whole kidney there's going to be less bleeding. But there still wasn't very much bleeding with this pole clamp, very low transfusion rate, but patients had better early kidney function which you would imagine because you're not stunning the whole kidney. Realistically this doesn't make a huge difference because long term the kidney function was the same whether you interrupted the blood flow to the whole kidney or just the part right around the kidney. The other thing that made application of robotic technology hard is that people come to us with different histories. People come with a history of colostomy or other abdominal surgeries that make our access to the kidney really hard. And so this is a patient that actually had bladder cancer and had his bladder removed. So what's unique about when you have your bladder removed is that that urine has to go somewhere. So you have to create a urinary reconstruction. And the type of reconstruction this gentleman had was called a colon pouch. So he has a colonic urinary bladder that just happened to be sitting right in front of his kidney where he has a new diagnosis of a kidney tumor. So if I tried to go through the front of his body to get to this kidney tumor this would be an incredibly difficult operation and I wouldn't want to damage his colon pouch. But this new ish technique of what we call retroperitoneal partial nephrectomy allows us to go through the back, stay completely out of the cavity where the intestines are and address this tumor. It's also really helpful for patients that have had extensive prior abdominal surgery because what I can do is go through the back and stay completely out of this compartment where I might have scarring or other complications that could make it a less safe surgery. It also helps for very difficult anatomic locations of tumors. So this is the front of the kidney. So this is the front of the body here. This is the back here. You can see the spine right there. I can go all the way around to the back. There's a tumor right here in the most toward the back location of the kidney. So five years ago this surgery would have taken me about six or seven hours because I'd have to free up the whole kidney, flip it all the way over. Hope I can see the tumor well and do a good job. But now I can just go right through the back and have much more facile access to this. So what does this look like? I showed my wife this video just because I wanted to see if it's interpretable and she said it just looks to her like a bunch of dog. But I'll do my best to show you what you're looking at here. So what we see here is this is the artery to the kidney and when I go through the back it puts me in a position just right on the artery which means I can be safe because it means I can interrupt the blood flow to the kidney. So you can see me creating a window above the artery and I've already created a window below the artery. And now I'm trying to find the tumor. The back side of the kidney. This is that gentleman with the colon pouch and what I didn't see during this entire surgery was his colon pouch which is great. Now here's his tumor and what I'm doing is I'm marking out a margin of normal kidney tissue all the way around the tumor and this is on the back side of the tumor so the tumor is right here. And now we're cutting out the tumor. Oh I'm sorry, no I'm not. I'm putting a clamp on the artery and I put two clamps on it so I want to make sure there's as little bleeding as possible and now we're cutting out the tumor. And so you can see I'm just using cold scissors and that way I can see normal kidney tissue plane and as we release the kidney up this way we're just coming underneath the tumor and what you see are these dark tan tissues and that's normal kidney tissue and now that tumor is lifted up and there's a nice plane of normal kidney tissue underneath. And so it's a very safe way to address a very complex tumor. We're using this argon beam clotery device and now we're just putting in some stitches to sew up the kidney. And so it took about four minutes to cut the tumor out and it took about 17 minutes to have clamps on the kidney so this patient only had interruption of blood flow to the kidney for, you know, a quarter of an hour. And so in a second we'll see a bunch of clips where we've kind of taken this open defect and cinched it together. You can see me cinching it right there. And so here's how it looks at the end. I'm going to put this stuff on top of it that's sort of like fake magic glue and now we're going to put that tumor in a bag. So I do a lot of robotic surgery but what's different about the way we do these surgeries in 2016 is I'm not a guy who has one hammer and everything looks like a nail. I want to be a kidney cancer surgeon not a robotic surgeon. So there's still a role for what we call complex open partial nephrectomy, open surgery. And that might be useful for patients who have just very complex tumors. Tumors that are so hard even though I feel comfortable with robotic surgery it's too much. But also patients where I'm worried they can't tolerate filling up their belly with carbon dioxide. Patients who have only one kidney I still don't do those robotically. I just think it's too dangerous when they only have one kidney I just don't want to mess with that. And the other thing is sometimes I can avoid interruption of blood flow to the kidney altogether because I can use my hand instead of an instrument. And these are some patients who have got complex open partial nephrectomies. This is actually the same patient and this is a pig just showing you kind of what we did. And this is showing you a tumor right on top of the main vein draining the kidney. Here's that kidney after we took the tumor out. So this is a little hard to see. This little yellow tape is encircling the main vein going into the kidney right underneath where we took the tumor out and this is sort of a schematic showing what we did. So the vein is right here and we almost took like a sharp bite out of the middle of the kidney and sewed it back up. What about larger tumors? A lot of people are talking about this. So if we can do this for smaller tumors can we extend the limits of this to tumors that are 5, 6, 7, 8, 9, 10 centimeters. And that would be great. But you know what? The complication rate goes up and not only does the complication rate go up but my concern about cancer safety goes up as well. So I always tell patients I have three priorities with this surgery. Number one is safety. Number two is doing a good cancer surgery. And number three is your quality of life. And if I'm concerned about cancer control and safety then I do think it's better to take the whole kidney out. That doesn't mean we don't do it. If I think it's safe and it doesn't compromise the cancer surgery I'll still do a partial nephrectomy with a bigger tumor. But I just want to make sure it's safe and it's good cancer surgery. So how do we follow up localized kidney cancer? This is a little tricky. One of the challenges with kidney cancer is that in general it's more likely to come back in the first couple of years after a diagnosis of kidney cancer but it can come back later. And it appears to correlate with the stage of the cancer. So in blue and yellow these are lower stage cancers and in red these are more aggressive cancers. And where you see circles this is where the risk of other cancer conditions outweighs the risk of their kidney cancer itself. And so if this circle is close to here that means that patient has an aggressive kidney cancer and needs to be followed aggressively. If that circle is way out here that means that patient has a low risk of a kidney cancer event relative to the risk of their other health conditions. So the idea is we want to change our surveillance schedule based on the aggressiveness of your cancer. So let's move on to the metastatic kidney cancer setting. What's unique about kidney cancer is it's one of the only cancers where there is a role for surgery on the main tumor even when that cancer has spread outside of the kidney to other parts of the body. And the reasons for that are largely unknown but it appears to be this relationship between kidney cancer and the immune system that there's just some benefit to getting that main kidney tumor out. Now that benefit has only been shown in randomized controlled trials in what Dr. Typhoni was referring to as the cytokine era. So we wanted to look if these newer drugs that we have for metastatic kidney cancer are better and they're more effective maybe that benefit of taking the kidney out is robust and so maybe it's not the standard of care to take the kidney out. And so what we see is we see that over time the survival rate of kidney cancer is improving when it's metastatic but it's not improving to the degree we'd like it to improve. Yet it still appears when we look at the larger population that it's beneficial to take out the main kidney tumor in someone that has metastatic kidney cancer. Can we describe that more robustly? So the problem is that if you're someone who's had your kidney removed and we're comparing you to someone that hasn't there is something inherently different about you. This was not a randomized controlled trial. So in general when we look at these patient populations the people that had their kidney removed are healthier, they're younger and so if you're going to have a big kidney tumor removed that already tells us something about you. So can we use statistical techniques that we say decrease selection bias that help us account for the differences in people that had their kidney removed and those that didn't? And what we see is this bar is below the line even as we use techniques that better account for the differences between surgical patients and non-surgical patients. And what this means is that all of our available techniques still show that in this modern era of targeted therapy or immune checkpoint inhibitors it's still beneficial in most patients to take out the main kidney tumor in the study of the metastatic kidney cancer. But that decision making isn't perfect. That doesn't mean that everyone with metastatic kidney cancer should have their kidney removed. In general these are some things that Dr. Taikoti and I talk about a lot. How we make these decisions and who is right for a kidney removal surgery. Well we think about that patient's risk category. Is this someone with what we call favorable risk metastatic kidney cancer or is this someone with poor risk metastatic kidney cancer? And if it's a favorable or intermediate risk kidney cancer we're more likely to prioritize taking out the kidney. If that cancer has spread the location where it's spread to is an important determinant of our likelihood of recommending kidney removal surgery. It's also nice if the surgery itself is what we call a debulking surgery. If by doing the surgery we're taking out a predominant source of kidney cancer cells in your body it obviously has to be removable but also we kind of weigh it positively if we can do laparoscopic or robotic surgery because we know that the recovery time is going to be minimized and so that means that lag until that patient can start treatment for cancer cells throughout the body is minimized. We're actually actively working on some decision making tools for this and this is not quite ready for prime time but this is based on ways to show patients data that shows individual trajectories. So our risk category tables if I tell you your favorable risk that gives me one number that tells you kind of the average survival of patients with favorable risk metastatic kidney cancer but that's an average. That doesn't tell you how many patients live for five years how many patients didn't live for a year and so what we want to show are individual trajectories and this was sort of based on a model of mileage for cars based on how many cylinders based on the number of different individual car parameters that influence their mileage. Well this shows you inputs from almost 4,000 patients from something called the international IMDC. What does that stand for, Scott? International multi... It's a multi-site consortium of kidney cancer patients. IMDC. So this shows you IMDC data. Now this is not meant to overwhelm you but this shows you that we can capture thousands of patient trajectories and this is their survival time. If we look at individual inputs this is looking specifically at patients performance status so how well they're doing from a physical function standpoint and in patients who are doing well from a physical function standpoint it gives us a real-time survival estimate of 50 months and as that physical function declines it automatically updates this and you can see that their survival estimate goes down. And so this is a tool that we are trying to better understand how to apply in clinical practice to see if in addition to our sort of gestalt impression of what the right thing to do is can we put a little bit of science on it to the decision making for use of surgery. We're also trying to figure out if we can help patients and clinicians make decisions about what therapies to use in the setting of metastatic kidney cancer. The last surgical thing I wanted to talk about is this idea of metastatectomy and this is the idea that in some patients with kidney cancer there is a role for removing metastatic deposits of kidney cancer so kidney cancer that spread to other parts of the body. This is very well described for patients that present with a kidney cancer and one tumor either in the adrenal gland or in the lungs. And we know that if we can take those out those patients do better. So there are a couple different occasions where we see this. Sometimes it's at the time when we do the initial surgery and we know that if we remove all of the lymph node metastases or adrenal gland metastases or we call in our thoracic surgery colleagues to remove a nodule in the lungs that we're benefiting that patient. Sometimes it's someone in whom we took their kidney out and now their X-rays show new deposits of kidney cancer elsewhere in the body. And sometimes it's when someone that Dr. Taikoti has been seeing has been doing well on systemic therapy and appears to have sort of a persistent deposit that we think, gosh, there might be benefit to removing that. And we know here that in someone who has a completely resected metastasis their five-year survival is better than someone who has a partially resected metastasis or who's not eligible for surgery for these metastatic deposits. And so I'm going to give you one anecdote. I am a surgeon and so we operate not as much by evidence but by anecdote. That's a joke, we do apply evidence. But this is a woman I've known now for seven years and when she initially came to me she had a large metastasis in her adrenal gland on the left side, so this is the left side where another doctor had taken her kidney out about ten years ago and she also had a small nodule on the right side. And so what we did for her was she had her left kidney removed back in 2007. She presented to me in 2012 and I took out her left adrenal gland in 2012. Because of that nodule on the right this was the only now existing deposit of cancer in her body but because she had been through a large open surgery and wasn't quite ready for another operation we gave her targeted therapy to kind of shrink or at least stabilize that tumor in the right. And then we came back and did what's called an adrenal metastatectomy and so this is just a short video showing you what we did. And so what's very difficult about the adrenal gland is it sits in this sort of anatomic knuckle that's quite difficult and so this is the liver and now this is the inferior vena cava the biggest vein in the human body and that crotch there is the vein to her only remaining kidney her right kidney so we want to take that very seriously and we're going to carefully dissect along that vein and then staple off the blood flow to and from the adrenal gland which is right here and then after that we can peel the adrenal gland off that kidney which is nice and healthy and pink and disconnect it and what you're going to see in a second is this kind of anatomic crotch where we see the liver up here the inferior vena cava and renal vein right here and the right kidney right there and everything else has been removed. So that was in 2013 and I just got a note from her in March of this year that she has not had any new deposits of kidney cancer grow up so that's an anecdote but it just does show you that there is benefit when it's technically feasible and possible to surgical metastatectomy. So a couple just summary thoughts about surgery for localized and metastatic kidney cancer it really is the gold standard for treatment of localized kidney cancer so when kidney cancer hasn't spread out of the kidney the main state of treatment is really surgery. I am a big believer that robotic surgery is a great facilitator and allows us to get away with small incisions and telescopic instruments where previously we had to do these big flank incisions through three muscle layers and it's associated with positive health outcomes in metastatic kidney cancer in well selected patients and that's our charge our charge is to help you make a positive decision about the role of surgery in the setting of metastatic kidney cancer and that metastatectomy if we can completely remove someone's existing cancer deposits can be incredibly beneficial and I'm happy to take any questions that people have. You talked about the role of debulking a tumor in the case of a metastatic situation. Is there any benefit to debulking a tumor if it's not metastatic or if it's of a lesser stage than metastatic? Yeah so the idea there is prevention of metastatic disease so if someone has a stage 1 through 3 kidney cancer and we remove it our hope is that we are curing that patient of the kidney cancer diagnosis so that they are not going to go on to develop metastatic kidney cancer. So just like a woman with breast cancer is going to have a lumpectomy and whatever treatments come after that to try to avoid developing metastatic breast cancer that's why we do those surgeries. Any other questions? Thank you very much.