 So let's let's get started Our first speaker is going to be young Kim Young's going to what is the optimal surgical approach for my upcoming kidney cancer surgery? I understand that many of you have already had your surgery But I think it's important for you to understand how the field has changed Just I met young first when we were UCLA and he was a urologic oncology fellow Young went then went to Roswell Park where he was a professor at Roswell Park Cancer Institute in Buffalo And came back to Cedars. How many years ago? Five years ago to lead our our kidney cancer surgical program And he's the co-medical director of the urologic oncology program and the associate director for research in the Department of Surgery young Yeah, thanks Bob. So It's a very nice to see you here. Welcome. You know I trained at UCLA a number of years ago now and when I went to UCLA for my fellowship I already knew I wanted to study kidney cancer because I felt it was a disease that at the time there was a Where you had a lot of room for discovery and improvement in patient care And then of course when I got there Bob was one of the faculty members I met and he was very instrumental in Teaching me about kidney cancer and helping to get my career on the right foot Now I'm a surgeon I Treat patients with urologic diseases, but my focus in my practice as well as in my research Remains kidney cancer So I'm going to talk to you a little bit about surgical approaches. Some of this may be review for you since Many of you have already had experience with kidney surgery Here's a picture. It's a picture from a from the operating room. This is how open surgery is done So for open surgery you have to make an incision We don't do operations this way very often. In fact, we do it so rarely I had a trouble finding a good picture and this one actually just came off the internet It's not even my picture, but it shows you how the operation is done you have a retractor a big metal device that's placed over the patient and you have these metal blades here you have these metal blades that are pulling on the On the skin and the rib cage is here and you're pulling the rib cage apart in some cases and It's very traumatic. It's hard on the tissue and it explains why patients have pain after surgery This is a picture of laparoscopic surgery It seems a lot gentler on the tissue You can see that Troll cars are placed and the openings that you end up with are about the size of keyholes The human hand is never in the body You use long instruments with little graspers at the end the television camera is placed and so this allows for a less traumatic and a minimally invasive operation Now you may have heard of robotic surgery Robotic surgery is really a just another way of doing laparoscopic surgery And I know many of you have had surgery five ten fifteen years ago So the robot may or may not have been available to you at the time But the robot doesn't operate on its own. It doesn't move on its own There is a surgeon who is sitting at a console and controlling the robot and This the robot essentially mimics the movement of the surgeon's hands So the surgeon sits there and whatever he does the robot mimics But the robotic hands are tiny there on their size of laparoscopic instruments. And so again, this allows Operations to be done in a less invasive fashion. This incidentally this Device was designed or conceived originally for the battlefield the thinking was If you're in battle, you don't want the surgeon to be operating on the front line where he he might get shot or Or bombed so you send in the robot and the robot gets attached to the patient and the surgeon can be Somewhere safer behind the front line doing the operation It didn't quite work out that way This is a two and a half million dollar piece of hardware and it was just too sensitive and delicate for battlefield situations But it found it's found a home and and you and and it's being actively used in modern operating rooms So here are some pictures of scars You can see that you know after an open operation. You might have a big Incision either in the front or along the side here's someone who's fully healed after laparoscopic surgery And if you look carefully you might see some scars, but they're barely visible now all your pain fibers are on your skin so that You know the size of your incision really translates into how much pain you have following the surgery And so you make a big incision you're gonna have more pain after surgery You're gonna have a longer recovery and you have to deal with the scar afterwards Now here's a a short video clip of of an actual operation where we're doing a laparoscopic Partial nephrectomy so you can see the tumor here and the tumor has now been cut off and This is the tumor bed Most of the kidney has been saved because we've just removed the tumor and a little margin of normal kidney and then you can see that you know, we're suturing and repairing the tumor bed and And we do this so that you don't bleed or leak urine from the side of the repair Right now you're not seeing bleeding because the blood supply to the kidney has been cut off We clamped the renal artery and vein and then once the repair is complete. We'll restore the blood supply to the kidney so and Robotic surgery if you were looking at a video would look very similar to this So here's the clamp the renal artery and vein are Are now patent and blood flow has been restored to the kidney and the operation is over So what do we know about minimally invasive surgery and when I talk is when I use the word minimally invasive surgery I'm talking about either laparoscopy or robotics It leads to faster post-op recovery What we do know now is that the cancer control Seems to be equivalent to that of open surgery the complication rates are pretty similar The operative time is a little bit longer with minimally invasive surgery because you're working with smaller instruments You can see here the changes in our use of various technology So right here on the x-axis you have here so 2005 to 2009 and you can see the percent of nephrectomies that are either partial nephrectomies or radical nephrectomies and You can see that over time We're doing more and more partial nephrectomies. What that means is in the olden days We would take the entire kidney out if it had even a small tumor on it The current standard is to take just a mass out and preserve as much of the normal kidney as possible Here's a table that really explains our rationale for doing partial nephrectomies so this is a study that was published in the New England Journal of Medicine back in 2004 and what it shows is that Your kidney function which is measured as GFR glomerular filtration rate decreases your risk of cardiovascular events such as a stroke or a heart attack increases so as your GFR starts to drop The risk of cardiovascular events goes up now. There is some controversy about this relationship It's not clear if it's a cause-effect relationship or simply an association That hasn't been nailed down, but I think many surgeons like myself Have decided we're not going to wait for the final answer if we can technically preserve Your kidney that has the tumor on it. We're going to do it Here's another important piece of data if you look at The National Health and Nutrition Examination Survey what it shows us is that Amongst patients over the age of 60 Reno pre-existing Reno and sufficiency Occurs in 40% of patients So if this is in the general population If you look at patients who have diabetes type 1 or type 2 again 40% already have Reno and sufficiency, so if you look if you look at the typical patient who develops a renal mass They're often over the age of 60 and they're often Diabetics and so we're often dealing with patients who already have Slightly decreased or significantly decreased kidney function and that would certainly argue for a partial nephrectomy rather than a Radical nephrectomy This is a study. We did a couple of years ago. There's a lot of information here But I've circled the numbers that I want to draw your attention to You can see that after a radical nephrectomy if you had normal kidney function Eventually almost 60% develop Reno insufficiency If you define Reno insufficiency as GFR less than 60 Now if you do that for patients who have had a partial nephrectomy only 15% Ultimately develop Reno insufficiency again showing that with a partial nephrectomy we can preserve kidney function and And that seems to make a difference long term Now this is a a normal grant we created a couple of years ago and you can actually access it online and It predicts for you what your kidney function might be after surgery and you can specify whether you do a radical nephrectomy or a partial nephrectomy you can put in the tumor size and If you've already had surgery and you've had a partial your surgeon may be able to tell you how long the blood supply to the kidney was Cut off during the operation and that information also gets put into the nomogram and it'll give you It'll predict your kidney function following surgery I'm going to shift gears a little bit and talk about kidney cancer and the risk of Recurrence following an operation for what was staged as a localized tumor so if you look at Just an example of a risk stratifier You could tumor grade is shown here You can look at patients with various grades of kidney cancer and you can look at their Survival over time and you can clearly stratify patients into different survival groups now For patients in this group Surgery alone may be sufficient But what about for patients in some of these lower groups where you know that the risk of recurrence even with surgery remains quite high Is there anything else we can do to try to prevent the risk of the cancer coming back? now this is a Slide that shows you the The therapeutic options we had you know ten years ago and This is certainly the situation when I was Training at UCLA and Bob was there as the faculty and and the Person leading the way and trying to develop new therapies for metastatic kidney cancer we had interferon and interleukin 2 and The situation is now quite different We have many more options for metastatic disease I've listed some of them here for you and these are small molecules targeted therapies that really Target the underlying disease mechanism Now these drugs are all approved for patients who have Established metastatic disease so lung meds bone meds But what about for the patient whose had surgery has no visible disease? But simply remains at high risk for recurrence. Can we use these drugs for those patients? The answer is maybe and in order to answer that question There are clinical trials that are being actively conducted. So this is a diagram of one such trial One of the largest if not the largest study that's ever been conducted or is being conducted in kidney cancer So this study takes patients who have had an nephrectomy, but remain at high risk for recurrence So they don't have no they do not have known metastatic disease But they're at risk for developing metastatic disease and they're randomized to Receive either sunitinib, soraphenib or placebo for a year, and then they're asking the question Does the drug decrease your risk of recurrence now? This study has enrolled all the patients they need for their trial and now we're in the follow-up phase to see if they Patients recur or not so in a few years We should have an answer from this study This is just a list a few of the other studies that are out there as well looking at other agents But the design is similar there. It's taking patients high risk for recurrence and asking if These various drugs such as soraphenib, sunitinib, pazaphenib, everolimus can be used in what we call the adjuvant setting But at this time we don't have an answer, but we should have answers Coming coming through very shortly There is another approach that I just want to mention to you you can give treatment after surgery But if you give treatment systemic treatment before surgery is called neo adjuvant therapy And I just want to show you one a couple slides that illustrate what neo adjuvant therapy may do It can decrease the risk of recurrence following surgery, but it can also decrease the size of the primary tumor in the kidney So here's a one of my patients that had this tumor in the left kidney and the tumor is very big It's going right to the middle of the kidney here And this is a tumor for which you would need to remove your entire kidney now this patient got sunitinib for two months and the Tumor shrink nicely, and it also takes on a much more Capsular up, you know well-defined Appearance with the nice capsule and this tumor was now amenable to a partial nephrectomy So here is the postoperative CT scan the tumor is gone There's just a little bit of bleed blood there from the operation But we were able to Preserve the kidney and this that was because we were able to give sunitinib before the surgery rather than waiting to give it after surgery and This is what we call a waterfall plot it Shows what happened to patients on this study if the bar is going in the negative direction It means the tumor shrink the bar is going in the positive direction the tumor Increased in size and so in this study that we did the majority of patients had some Amount of tumor shrinkage some had very dramatic tumor shrinkage and some had a little bit but And then there were even some patients where the tumor continued to grow but the majority of patients had tumor shrinkage and it's possible that First many of these patients the surgery was easier and And perhaps you could convert from a radical to a partial nephrectomy Here is a anatomical diagram of The kidney and the lymphatic drainage of the kidney This is a picture that we drew but it was based on Anatomic drawings from almost a hundred years ago our understanding of the lymphatic anatomy hasn't changed in many years But it shows you that you know the kidney has these lymphatics and that's why when you have a tumor on the kidney often the the lymph nodes get enlarged and the tumor spreads to these nodes and One of the important questions when doing surgery is do you need to sample the nodes or not? And here's a study that we did which shows that if you don't do a node dissection You're not going to find positive nodes But if you do a node dissection as part of your kidney surgery you find nodes even though the Preoperative CAT scan was negative so it clearly leads to better staging and knowing the node status Improves your ability to Determine prognosis Another way to determine prognosis is Molecular markers so As we In talking about molecular markers I need to tell you a little bit about what's been happening with our ability to measure markers so the human genome project Sequenced the entire human genome for one person who lives who lived in Buffalo, New York and the cost of the project was 2.7 billion dollars and A couple years later a study was Published where they did it sequenced the one individual and his tumor and that was in 2008 and the entire project cost $700,000 now the Back in 2011 it was possible to do a sequence the entire genome the entire blueprint for an individual For $5,000 and it took two days now We're actually at this point where you can do that same work for a thousand dollars and one day So what is this allowed us to do? Well, it allowed us to take tumors that are stored in our biobank so this is an example of a Biobank that we have where you store blood and tumor samples and You can sequence them and here's an example of a paper that just came out in One of the leading journals nature and they took over 400 kidney tumors and sequenced them all so not only are we not we're not talking about the sequence for one individual but the sequence for Hundreds of tumors and this allows us not only to understand what's happening in kidney cancer, but understand the variability amongst tumors and We take that information and apply it to tissue from clinical trials like this one. This is a study that was done a number of years ago and patients either received inner furan or inner furan and Bevizuzumab or Avast and and this is a study that led to FDA approval of Bevizuzumab so in one of the studies that we're currently working on we took tissue from this trial from patients who went on the study and We profiled molecular markers using some of the newest genetic Techniques that are available to us and here's an example of a marker that we discovered where the Where if the marker is high you are better off getting Interferon if the marker is low you're better off getting inner furan plus Avast in so we're discovering Markers that can stratify prognosis as well as teach us what kinds of therapies might be best for patients so this is just an example of how we are using modern technology to go beyond things like Assessing live node status and and and to determine prognosis and pick therapy So I want to just leave you with these concluding thoughts I believe that a partial nephrectomy should be performed when it's technically feasible and it doesn't it's Whether it's done laparoscopically or using an open approach is probably of second importance, but of course laparoscopy will lead to faster recovery and And I believe that people should consider clinical trials of adjuvant and neo adjuvant therapy so we can You know you have an answer soon as to their effectiveness and we do know that a retro perineal lymph node dissection improves staging at the time of surgery and We're actively working on molecular profiles and molecular markers to try to personalize therapy and go beyond the traditional staging Systems that we currently have Thank you for your attention We have time for one or two questions if there are any from the audience the microphones in the front Maybe I can start young Many people who are now presenting with katsuki and evidence of small renal masses Sometimes undergo procedures that are not surgical. Can you make a comment about that? Yeah, so what we also what we now know is that many of these small tumors that we find incidentally May never grow or may take years and years to grow and so if you have an older individual who maybe has a Limited life expectancy you may not necessarily have to treat and so what we recognize is not everybody needs treatment and certainly not everybody needs treatment right away and so You know it's important to ask your doctor what the prognosis is and if treatment is absolutely necessary Thanks young so let's move on