 So I'm going to talk a bit about the management of locally advanced disease So this basically this means that you know tumors that are more advanced more larger potentially involving the lymph nodes potentially involving the venous system That are associated with a worse prognosis as compared to those tumors that dr. Mateen was talking about So I'm going to touch a little bit on adjuvant therapy adjuvant therapy basically means Patients always ask is there something that I can do Some medicine I can take some radiation I can take that will decrease the risk of recurrence That's adjuvant therapy and then talk a bit about node dissection and then management of venous tumor thrombi So just a word about adjuvant therapy. There is none There is no role for chemotherapy or radiation or targeted therapy or any therapy after surgery In the absence of clinically detectable disease So if you do not have obvious evidence of metastatic disease on your CAT scan There is absolutely no role for systemic therapy or radiation after surgery That's not to say we haven't tried and actually md. Anderson and Other centers have done clinical trials that have examined a variety of different agents including vaccines immunotherapy with interleukin 2 and interferon A variety of different chemotherapy regimens and most recently The targeted agents seraphonib and synitinib which have shown so much promise in the setting of metastatic disease But what we were able to show with a very large Literally international clinical trial Is that they don't decrease the risk of recurrence So when patients have surgery it's not uncommon to have them asking you know in the recovery room Am I going to need chemo am I going to need radiation the answer is no None of those agents work So moving on to lymph node dissection What are the clinical questions that are relevant with regards to whether or not a lymph node dissection should be performed? First obviously who should have one or when can it be avoided should it be based on tumor size stage histology? Or on the size of the lymph nodes based on imaging or interoperative assessment There's debate about what is inadequate lymph node dissection should it be just the hyalum where the blood vessels go into the kidney should should it be Clearing off the ipsilateral grade vessel the vena cava or the aorta should it be a full bilateral dissection? There's no real agreement on what constitutes an adequate lymph node dissection And then the last question is can an adequate lymph node dissection be performed? minimally invasively More and more as dr. Mateen pointed out we're doing these surgeries minimally invasively and it becomes a question as to Whether or not you can adequately do a lymph node dissection using that technology So this is going to be a little bit of a case-based approach. Here's a patient. You can see he has a very tiny little tumor Sitting on the back of her right kidney And I think we can all agree that this patient probably is not going to benefit from a lymph node dissection Um arguably she may not even need her primary tumor treated as dr. Mateen had pointed out during his lecture Uh a biopsy may help us guide further therapy Although there are some exceptions where even these tiny tumors if they have these histologies can behave in aggressive manner And now here's another patient with a very large locally advanced tumor involving the right kidney And actually has evidence of clinically involved lymph nodes. You can see there's some large lymph nodes here and here This is the aorta. There's some nodes on the side of the aorta as well So Can we all agree that basically in this setting we're probably going to perform an aggressive lymph node dissection? Although the benefit really is unclear The knowledge of histology may play a role But arguably surgery for this patient with an aggressive resection is his best chance of cure If cure is possible and we can argue about whether that's uh the case But here are the here are some cases where the role of lymph node dissection is very unclear So here's a patient with a locally advanced tumor involving the right kidney. No evidence of any lymph node involvement at all Here's another patient with a very large tumor involving the right kidney With no evidence of any lymph node involvement at all and the question is whether or not this patient should undergo lymph node dissection And would they benefit from it? Well level one evidence which means You know based on clinical trial evidence that i'll show you There is no role for a lymph node dissection in these patients It's quite possible that just removing the kidney may remove lymph nodes as a sort of a collateral damage type technique People argue that we should remove lymph nodes to better stage patients And staging may be relevant in predicting prognosis and stratification for adjuvant trials But as I told you Knowing the stage doesn't mean that we have some magical treatment that we can give that patient to decrease the risk of recurrence We don't have any And really the clinically relevant question is are these patients likely to fail regionally meaning in the lymph nodes Or distantly meaning removal of the lymph nodes is not going to change their outcome Or both Well the data and literature would suggest that if we look hard enough we will find evidence of nodal disease This was a study that was published some years ago And what they noted was in patients who had locally advanced tumors If they removed more than 13 lymph nodes the rate of positivity was almost one third So nodal disease does exist and does occur And arguably you would believe that if we can remove it safely that patients would do better But there's actually no prospective evidence to suggest that that's the case These are data from the Mayo Clinic where they looked at where lymph node or where kidney tumors metastasize where the nodes are positive And that's this has helped better frame what actually constitutes an adequate lymph node dissection So they noted that in patients with right-sided tumors The overwhelming majority of lymph nodes are going to be in the right Or in between the aorta and the vena cava and very rarely will they metastasize over to the left hand side And the same is true on the left hand side where very rarely will they metastasize to the right so We know where the positive lymph nodes should be And we know what nodes have to be removed to adequately detect them The question is whether or not we're going to impact outcome by doing such a thing These are data looking at sentinel lymph node detection. Basically they inject Radioactive material into the primary tumor and then look where that radioactive material goes And again, it demonstrates basically the same findings as the Mayo Clinic study did That the nodes will end up on the ipsilateral side as well as in between the vena cava and the aorta Suggesting that we again know where the nodal disease should exist The question is whether or not removing it is going to change a patient's outcome The vast majority of the studies looking at lymph node dissection are retrospective. These are data from the University of California, Los Angeles Where they noted that patients who had no evidence of clinical node Involvement it didn't really matter whether or not you did a lymph node dissection their outcome was exactly the same But for the first time Their data suggested that in patients who had clinical evidence of nodal metastases meaning that they had in large lymph nodes If you remove those lymph nodes patients did better than if you left them in place We did a retrospective study looking at the role of aggressive surgical resection in patients who had positive nodes We identified out of a group of three more than 3000 patients 68 patients who had positive nodes in the absence of metastatic disease. So it's actually quite rare To have lymph node metastases and not have other sites of metastases again suggesting that lymph node dissection May not play a major role in in helping patients survive their disease What we noted was that those patients who had papillary histology had a better outcome Those patients who only had one node that was positive as opposed to multiple nodes had a better outcome Those patients who had sarcomatoid features had a worse outcome And their performance status meaning how functional they were at the time of surgery played an impact in terms of their outcome But what we noted was it almost half of the patients that we operated on were disease free at 12 months And you might say wow only half I would argue that these are patients who have obvious evidence of metastatic disease and that the fact that half of them Were disease free without any additional treatment at 12 months is pretty remarkable There is one Randomized trial that was done over in europe where they asked the question Does lymph node dissection play a role in the treatment of patients with kidney cancer? And so basically patients with kidney cancer were randomized to either get a lymph node dissection or not get a lymph node dissection It was a very large trial and unfortunately at the end of the day They were unable to demonstrate a benefit of lymph node dissection And patients with kidney cancer, but if you look a little closer at the trial You'll notice that the overwhelming majority of patients that were enrolled in this trial Were actually the least likely to harbor lymph known metastases and in fact the incidence of lymph known metastasis in this trial Was only three percent So while this trial was a negative trial suggested that there is no role for lymph node dissection Others would argue that this trial is underpowered to actually demonstrate a difference and actually should be redone Focusing on the more advanced stage tumors that are more likely to harbor nodal metastases The group from mayo clinic were able to demonstrate factors that predicted for nodal metastasis including nuclear grade The presence of sarcoma toy de differentiation tumor size tumor stage And the presence of histological tumor necrosis and in fact at the mayo clinic All kidney tumors are sent for frozen section at the time of surgery and if they have a variety of these different features It triggers a node dissection basically anybody that has more than two of the features that I outlined earlier Are scheduled to undergo a lymph node dissection with a higher incidence of nodal positivity detected These are data from over in europe where they tried to predict those patients most likely to harbor nodal metastases And what they noted in their study was that those that had an advanced t stage Evidence of clinically positive nodes meaning in large nodes on cascanner at the time of surgery The presence of metastases and tumor size all were predicted of patients having nodal metastases Last year We published our experience trying to predict patients who were likely to harbor positive nodes And we noted the performance status The presence of clinically enlarged nodes local symptoms related to the tumor and ldh We're all predictive of having positive nodes at the time of surgery And so moving forward we can use nomograms such as this To try and better identify patients who are likely to harbor nodal disease and benefit potentially from a node dissection So here's a patient with a locally advanced tumor involving their right kidney And this patient's likely to have a laparoscopic surgery And really the question is can an adequate lymph node dissection be performed laparoscopically and what exactly is adequate? I would argue that in the vast majority of cases This patient will not undergo a lymph node dissection and just have their kidney tumor removed with the kidney Here's another case of mine, uh that presents You know the potential problems would not performing a lymph node dissection This was an 81 year old gentleman who was undergoing evaluation for a pulmonary embolus none was found But he had an incidental finding of a right renal mass He had novencin metastatic disease and he had what I would classify as a Surgically hostile abdomen. He had multiple previous surgeries and you know, basically I was not looking forward to going through his abdomen to try and take out his tumor Here's the tumor involving the right kidney right here And so what we decided to do instead of going through the abdomen and potentially causing all sorts of problems with his Intestines and a stomach and his colon and so forth We went into a flank incision and just removed his kidney And there was the pathology was a type 2 papillary kidney cancer that was invasive into the renal pelvis and renal vein But we had negative margins Everyone high five the guy did well. He got out of the hospital and went home But then two years later Here is a positive note sitting in the middle of his Between his vena cava and his aorta and arguably if I had you know Bitten the bullet and taken the patient to the operating room and went through his abdomen and did an adequate node dissection This uh complication would not have occurred So we had to take the patient back. He was now older He had more medical problems and we identified the two of 28 lymph nodes were positive for metastatic disease So I would argue that the patient probably would have been saved from a second morbid surgery Now these older and more medical issues if I had done an initial lymph node dissection However, again, it's unclear what the impact of that would be Here's another patient this patient has a locally advanced tumor involving their right kidney With metastatic disease and the role of lymph node dissection in the setting of metastatic disease is completely uncharted waters But we performed a site reductive nephrectomy remove the kidney Remove multiple lymph nodes associated with the kidney and postoperatively the patient came back and If you can see all this sort of gray material surrounding the liver. This is the liver here. This is the stomach This is all fluid. It's called kyla societies And basically what it means is that when we did our lymph node dissection We tried to do a good job of clipping all the lymphatics that we cut But we didn't clip clip them all and so lymphatic fluid was leaking into the abdomen And this patient required a drain placement She had to go on a no-fat diet and had to get intravenous feeding to try and stop that lymphatic flow And as a consequence, she couldn't go on to get chemotherapy that she required for her metastatic disease So I would argue she definitely didn't benefit from a lymph node dissection and actually probably was harmed by it so Many urologists look to the guidelines and we all talk about guidelines as you know ways that we can sort of better Gage our behavior in the clinic. So these are the data from the european Urology association where basically they recommend that lymph node dissection should be performed on everybody Now I think that this is probably overkill. There clearly are patients who are not going to derive benefit from Lymph node dissection. I'm really not sure what the benefit is in the metastatic setting I think at patients who have clinically positive nodes aggressive resection is probably warranted I also think in the setting of locally advanced disease that doing a lymph node dissection to better enhance staging And potentially cure some patients who harbor micro metastatic disease. It's probably warranted However, I really don't see the benefit in lower stage disease such as t1 and t2 So the role of lymph node dissection and locally advanced disease remains undefined The evidence for improved curates with lymph node dissection is lacking We don't have any data to suggest that even if patients have positive lymph nodes That taking that disease out is going to make them live longer or do better People argue that improved staging and locally advanced disease is really the only argument to do a lymph node dissection But that somehow implies That if we know that the patient has a more advanced stage that we can do something to change their outcome And as I told you we have no therapies that we know of that will do that The benefit of lymph node dissection with clinically negative nodes in the setting of metastatic disease is completely uncharted waters And really needs to be evaluated in the context of a clinical trial I think the overall message is that we need to do a better clinical trial That specifically asked the question of what is the role of lymph node dissection in the setting of advanced disease And until that trial is done really there is no guidance with regards to whether or not we should be doing lymph node dissection And patients who present with locally advanced kidney cancer So I want to move on and talk a little bit about the management of venus tumor thrombi, which is something that Many people feel is unique to kidney cancer. It's actually not But it is a common finding happening in about 15 percent of patients who present with locally advanced kidney tumors So here's a classic example This is a patient of mine who has a locally advanced tumor involving the right kidney It seems to me I've shown you every single patient I've shown you today has had a tumor involving the right kidney It does actually occur on the left as well. I'm not sure why they're all right Uh, and here you can see there's a tumor thrombus extending up Into the venus cava and actually extends all the way up into the heart And here you can see tumors sitting in the right atrium of the heart without metastatic disease And this patient actually under one surgery And was cured after her surgery So venus tumor thrombi occur most often with patients who present with clear cell renal cell carcinoma But actually can occur with all different types of kidney cancer And actually can occur with a variety of other non renal retropartanial tumors such as urethial carcinoma adrenal tumors Wilms tumor, which is another tumor of the kidney as well as metastasis And actually this was a patient who presented with testicular cancer at a venus tumor thrombus So it happens as I said approximately 15 percent of cases of patients with kidney cancer actual Just renal vein involvement is fairly common It happens in about a third of patients but more extensive involvement involved with the venus cava or atrial extension is much more rare These are the different symptoms that patients can present with when they have venus tumor involvement And it's remarkable that almost 20 percent of patients actually have no symptoms Despite having extensive involvement of the venus system With regards to evaluation MRI is the gold standard However, with multi detector CTs the sensitivity has increased dramatically But most people still prefer an MRI for evaluating venus tumor thrombus involvement Because of the lots of additional information it can provide So here's a typical case Of a patient who has again a right-sided tumor with a venus tumor thrombus extending up to almost the retro patic venus cava But you can also see evidence of bland thrombus meaning just blood clot Involving the lower venus vena cava. You can see evidence of venus collaterals So MRI is actually very good for better staging IVC thrombi and looking for evidence of bland tumor thrombus and again allows for better surgical planning When you take these patients to the operating room It's important to get updated imaging I try to get imaging on patients within a week of surgery because the thrombus can progress rapidly You can take a patient who you believe has a level 2 thrombus to the operating room And then when you get in there find out that the tumor thrombus has grown dramatically And changes the complexity of the operation Most of these patients will start on anticoagulation to prevent them from having pulmonary emboli and improve blood flow There's such a thing as called an IVC filter Which is basically a screen that you can put into the vena cava To prevent blood clot migration Many people will put them in for these venus tumor thrombi However, it changes the complexity of the operation to remove the venus tumor thrombus Dramatically, so it encouraged no IVC filters should be placed preoperatively Again, these all relate to surgical planning If there's evidence of venus wall involvement Then we would want our cardiovascular surgeons to be available to help potentially reconstruct the vena cava And this is a retrospective study that demonstrated that the diameter of the vena cava and the renal vein Help to predict whether or not the vena cava wall is actually invaded by the tumor There are a variety of different staging systems out there And what this basically allows us to do is make sure that we're all speaking the same language When we're talking about venus tumor thrombi when we talk about a level zero versus a level one versus a two three or four That we're all speaking about the same Level of involvement of the vena cava and this one for the Mayo Clinic is the most common Staging system that's used out there So just step by step, how do we take these things out these this Probably is one of the most complex operations that urologists do First and foremost make sure that you have a very experienced team assembled that includes liver surgeons vascular surgeons as well as the urologist Um, this is primarily a vascular operation not a cancer operation And it's important that you operate on the vessels first To try and get the tumor thrombus out before removing the kidney So basically you ligate the renal artery to cut up blood flow to the kidney and to the uh Tumor thrombus isolate vena structures remove the thrombus remove any distal bland thrombus Fix the vena cava and then actually perform the nephrectomy to get out the the cancer and perform lymph node dissection So these are a variety of different scenarios I won't belabor this but basically for a free floating tumor thrombi the operation is very straightforward You just basically make an incision At the level of the renal vein extract the thrombus and then close it For patients who have evidence of blood clot distally in their in their lower extremities You can put in this vena cava filter here to prevent uh migration of this tumor thrombus and prevent pulmonary emboli And patients who have actually clotted off their vena cava because of a low flow state related to this tumor Thrombus plugging up the vena cava You can either staple or even transect The vena cava to prevent harm from this bland thrombus migrating and causing a pulmonary emboli But these are thankfully exceedingly rare So again, just highlighting this is primarily a vascular operation So this is a patient with a venous tumor thrombus and the first thing that we did was place ties on the renal artery To cut off blood flow to the tumor as well as to the tumor thrombus Uh, and then worked on the vena cava to extract the tumor thrombus So these are some cartoons that hopefully will show it more graphically for you So this is a patient with a level one or level two thrombus You can see the tumor thrombus here and basically it's you know like plumbing basically you get control above You get control below you control the contralateral renal vein And then you incise the os extract the thrombus and then just close the cave otomy It gets a little more complex with more advanced tumor thrombi Here we had to mobilize the liver to allow us to get higher on the vena cava to extract the tumor thrombus Oftentimes we'll use something called trans esophageal echocardiography So basically it's an ultrasound that passes down the throat into the esophagus To allow us to monitor the height of the thrombus and look for evidence of migration of the thrombus on real time In terms of level four, which means tumors that extend up into the heart They talk about veno-veno bypass something i've never used before but we have used Cardiopulmonary bypass where you open up the chest and put the patient on cardiopulmonary bypass and stop the heart To allow us to extract the tumor thrombus from the heart and then restart the heart after the tumor thrombus has been extracted And the vena cava repaired And even though this tumor thrombus is extending all the way up into the heart these patients still can be cured Approximately 50 to 60 percent of patients who present like that will be cured at five years out from surgery This slide just talks briefly about the devastating complication of pulmonary embolism So during the course of the surgery as we're moving things around to try and take out the kidney and take out the tumor thrombus A vast minority of patients will actually have migration of that tumor thrombus up into the lungs I've seen it happen twice. It's quite dramatic And the patient could actually die on the table as a consequence of this But in this particular series of patients, they reviewed nine cases where the patient had embolized their tumor thrombus They were put on cardiopulmonary bypass Hypothermic arrest was treated was used in for the patients and you could see the outcomes Uh, the overwhelming majority of patients did die of kidney cancer However, a significant number of patients were alive and had no evidence of disease So even though the tumor is involving the vena system, it doesn't mean that it's metastatic And it doesn't mean that the patient's destined to die from metastatic kidney cancer These are data from our institution where we again looked at the role of Surgery in patients who presented with pulmonary emboli and noted that those patients who had pulmonary emboli Had a very similar outcome to patients who presented without pulmonary emboli suggesting that the embolus was not necessarily tumor and possibly could be bland thrombus So what about the role of the robot? Dr. Mateen talked about the role of the robot in patients who presented with small renal masses What about in these patients who present with locally advanced disease? Well, there is literature out there although it's very a small amount of cases Here's a patient who has a locally advanced tumor involving the right kidney with an IVC thrombus You can see they put a vessel loop around the renal vein They opened up the vena cava here. So the tumor thrombus here you can see it better here And they extracted the tumor thrombus and then sewed up the vena cava So I think it highly select cases it is possible to use the robot to treat these patients But I would argue the vast majority of patients are ultimately destined to be treated with open surgery Here's another case Published by the same author where you had a locally advanced tumor involving the kidney with a venous tumor thrombus It extended down into one of the branches of the renal vein And this patient underwent a partial nephrectomy with the venous tumor thrombus extraction done robotically Again highly select should be done by pay by surgeons who have a lot of experience working with the robot But I would argue the vast majority of cases are likely going to be treated with open surgery And here this was a retrospective review of inferior vena cava tumor thrombus surgery done robotically You'll note that this was published in 2014. Only nine robotic cases had been published in the literature So this just looks at outcomes. We looked at our experience with patients who presented with IVC tumor thrombi. We had 605 patients over A number of years A median age was 60 follow-up was two years. You can see the vast majority had just renal vein involvement Although a significant percentage Did have evidence of involvement of the vena cava 45 percent of patients presented without evidence of metastatic disease The median blood loss was almost a leader. These are very bloody operations There was a 25 complication rate within the first 30 days And if you had no evidence of metastatic disease, your outcome was quite good The overall survival was more than five years However, patients who presented with nodal or distant metastases their outcome was significantly worse related to their metastatic disease 12 patients died as a consequence of surgery There was one intraoperative death and then 10 who died Within 30 days of surgery and one patient who had a mass of PE approximately three months out from surgery So the point is that the surgery despite being very complex and major Is safe So we looked at a variety of different variables to predict outcome. They're listed here The bottom line is we found that patients who had clear cell histology had a better outcome than those that did not Patients who had high grade disease or sarcomatoid de-differentiation Evidence of fat invasion nodal metastases or distant metastases all of those factors were associated with the worst outcome In patients who had IVC tumor thrombi We noted that patients who had tumor thrombi that extended up into the heart had a worse outcome than patients who just had involvement Of the vena cava below the level of the diaphragm And in comparing our series to other series that have been published in the literature in the past outcomes are very similar I'm going to pass through that This was looking at a finding that was really sort of surprising to me We looked at 270 patients who had venous tumor involvement And we noted that almost 20 percent of patients had cancer present at the margin And positive margins were more likely in patients who had a higher level tumor thrombus or those that had a higher grade tumor And so I looked at this data and I said wow, maybe we should do something to change our technique If more than almost 20 percent of patients had cancer present at the margin of resection And those patients were more likely to have a local recurrence and more likely to have metastatic progression So my thought was well, maybe we should change our Operative technique and check margins at the time of surgery and those patients that had positive margins Maybe we should you know resect more of the vena cava or maybe even resect the entire vena cava and reconstruct it But in fact if you actually look at how these patients recur The overwhelming majority of patients who had positive vein margins in the blue here Progress with metastatic disease And this would argue that changing the surgical technique or being more aggressive locally is not going to impact their outcome overall Because the vast majority are destined to progress with metastatic disease suggesting that this is a reflection of the biology of the tumor Not some inadequacies in the surgical technique Okay, I'm going to skip over this because it's not relevant So suppose we don't operate on these patients in in many cases Urologists out in the community are quite daunted by the prospect of taking one of these patients to the operating room Because of the complex nature of the surgery well This was a retrospective study looking at conservative management of patients who present With iBC tumor thrombin you can see the patients that are not operated on do poorly systemic therapy alone does not work in these patients This was a study out of the Mayo Clinic that showed this exact same thing So what about the role of systemic therapy in the treatment of these tumors many times patients out in the community Will be started on some form of targeted therapy And be and told that this this targeted therapy will make your tumor thrombus shrink and make your surgery easier And there are multiple anecdotes and literature Suggesting that starting patients on targeted therapy will dramatically reduce the size of their tumor thrombus Well, we published a retrospective study looking at the role of targeted therapy in shrinking tumor thrombi Long story short the bottom line is the vast majority of patients had little to no Impact on their tumor thrombus as a consequence of systemic therapy There were three patients that did have some decrease in the level of their tumor thrombus But the vast majority had little to no impact We did another study where we looked at patients with metastatic disease treated with targeted therapy We had 48 patients who had venous involvement And again the very similar story that the vast majority of cases Had little to no impact on their tumor thrombus as a consequence of being treated with targeted therapy You can see 75 percent at stable disease. And in fact 15 percent of patients actually grew while they were getting the targeted therapy So I would argue that there's little to no benefit from systemic therapy and treating patients Who present with venous tumor thrombi and that surgical therapy remains the gold standard Then lastly i'm going to talk about one of the devastating complications associated with The venous tumor thrombi and that's bud kiari syndrome. So basically if the tumor thrombus grows big enough It can grow past the hepatic veins and actually cut off blood flow draining from the liver and you can see this sort of Flow defect in the liver that's consistent with a bud kiari syndrome and patients will present with abdominal pain They'll have a cites, which means fluid in the abdomen. You can see there's fluid in the abdomen over here Uh, hepatomegaly meaning enlargement of the liver lower extremity edema and abnormalities in their liver function tests In our hands if patients present with this syndrome and we take them to the operating room the in-hospital mortality rate is in excess of 80 percent So basically the overwhelming majority of these patients if you try to operate on them will die So what we do now instead of taking them to the operating room is we will embolize the kidney Meaning to cut off blood flow to the kidney in the hopes that this vascular thrombus Will shrink as it did here and you can see that there's shrinkage of the tumor thrombus There's blood flow Occurring in the vena cava around the tumor thrombus. You no longer see that perfusion defect in the liver And after three months of allowing this tumor thrombus to shrink We were able to take this patient to the operating room and cure them of their kidney cancer So radical nephrectomy with ibc thrombectomy is a very demanding surgery that can be associated with significant side effects and mortality But in the absence of metastases or nodal disease or sarcomatoid de-differentiation or fat involvement Um, it does appear to be associated with an excellent prognosis Minimally invasive approaches are described But I would argue is not the the standard of care and patient selection appears to be critical In terms of better selecting patients for minimally invasive approaches And presurgical treatment with either embolization or targeted agents does not appear to be helpful And in fact may worsen a patient's prognosis So that's basically a sort of summary of how to treat patients who present with locally advanced disease again The take home points are adjuvant therapy does not exist in 2016 The role of lymph node dissection is unknown, but in locally advanced disease It's probably advocated and the management of ibc thrombi can be quite challenging But patients will still have excellent outcomes as long as they're treated at major centers by people who have experience