 My job today is to talk to you about options of treatment when we have a local recurrence meaning recurrence after initial therapy and I'll get into some more definitions here in a second. I don't have any relevant disclosures for this particular presentation. For definitive treatment what I mean by that is a treatment that was done aiming for cure and these are treatments that Dr. Schuck mentioned earlier such as ablation therapy which could be with cryotherapy or radiofrequency or microwave or with surgery which could be either open or laparoscopic or robotic and it could be a partial nephrectomy where we save part of the kidney or a radical nephrectomy where we take the entire kidney out. So this is what I mean for this purpose of this talk definitive treatment and to define an isolated local recurrence I'm going to use the following definition. So it's the recurrence of a cancer that we already treated. It's a cancer that we treated with the intention to cure but something happened and it recurred again and the location is in the retroperitoneum which Dr. Speace just mentioned to you where that location is so it's basically deep in the abdominal area close to the major blood vessels like the aorta and the vena cava and it could be in the kidney itself. It could be where the kidney used to be if we've already removed the kidney. It could be in the lymph nodes close to the kidney or in the adrenal gland which is a tiny gland that we have on top of each of our kidneys and generally when we talk about local recurrence only or an isolated local recurrence it means there is only recurrence in this retroperitoneal area but nothing elsewhere so no bone metastases or liver or lung metastases. The question is how often does this happen? With ablation therapy generally if the patients are selected well it should be less than 10% with partial nephrectomy it should be less than 5% and with radical nephrectomy it should be less than 3% again this is in isolated local recurrence so thankfully this is a rare event as you could see here and that's why most of the manuscript I will discuss are small series of small number of patients and they're not that many patients which is a good thing. The question is how do we actually find this local recurrence and there's two main ways to find it either by routine imaging so let's say you're going to see your doctor every six months or every year something shows up that's one way to diagnose it in general these tumors would be asymptomatic meaning you don't feel anything it just shows up on the images or the other way would be if there are symptoms so if a patient has you know new pain that was never there before and they feel that in the area of the surgery if there's bleeding that wasn't present if the patient suddenly is feeling tired and they were doing just fine before that or if the patient's having unexplained weight loss or the patient's feeling amassed now somewhere in the abdomen these are signs that you should bring up to your doctor immediately just to make sure that they're not related to the cancer that was treated in the past and the possible scenarios in this situation are two so you can either have an isolated local recurrence so just a recurrence in the area of the initial procedure and nothing else and this is the best case scenario or you could have a recurrence in that area plus a metastasis such as in the long or bone or liver and this is a less favorable situation at that point and the options are many so the treatment options we're going to go through here are really the same as treating a patient that has never had treatment before so we can do observation or active surveillance we can do ablation we can do surgery radiation is an option as well and systemic therapy and i'll go through each one of these as far as the individual patient approach so let's look at the guidelines there are the american urological association guidelines the european guidelines and the national comprehensive cancer network guidelines and none of these guidelines really tell us what we should do when we find an isolated local recurrence and the reason is it's a quite a rare phenomenon and there aren't large studies to really guide us so it's a very individualized approach that we have to work with with each of our patients so there are no general guidelines in this type of setting so after we find the local recurrence we need to make sure if the patient has a metastasis or not so we can just look at the ct of the abdomen and go for surgery we have to do a thorough work up at least we have to look at the chest with a ct of the chest we have to personally review the MRI or the ct of the abdomen and if indicated we should do an MRI of the brain or a bone scan among other studies to make sure there isn't any cancer anywhere else if the suspected recurrence is very very small there's nothing wrong with just waiting and repeating the imaging for two or three months it could still be healing from the surgery for example it could be just a small amount of blood that's going to disappear if we wait a few months so waiting if the suspected recurrence is very small is okay to do so and a biopsy can be done sometimes if it's clinically indicated meaning if it's not sure what it is if it doesn't look like a typical recurrence it's okay to do a biopsy but it's not mandatory in this setting and the decision on how we treat our patient is very individualized and there's two main categories of factors we look at the first one is the patient factor and like Dr. Spiece was mentioning you know age is very important the performance status meaning is the patient able to perform activities of daily living or if the patient in a wheelchair or bed bound these will guide us to different therapies for different patients how is the kidney function is the patient have comorbidities you know strokes or high blood pressure or heart attacks and things like that in the past does the patient have other cancers that are active and that's something we see in our hospital because patients sometimes have more than one cancer as well and also to have a frank discussion with the patient about what their wishes are and what they expect from their treatment we have to be realistic when we discuss things with our patient and we have to understand and listen to what our patients want and expect from their treatment if they expect to be cured and we cannot offer cure we have to be honest about it if they expect palliation meaning just to feel better and that's something we could offer potentially that's something that we can do for our patients so we have to have a frank conversation whenever we discuss a local recurrence treatment and of course we have to keep in mind the tumor factors such as the size of the tumor the location of the tumor how fast the tumor is growing and the results of the biopsy if we have the biopsy result this is the brief outline of where i'm going to go through as far as the frequency of follow-up and that's very highly debated because we don't have one guideline that we can follow as much as how often do you see your doctor and i'm sure if i ask you in the room here how often do you see your doctor for follow-up everybody will say something different and that's normal that's to be expected actually and i'll discuss the recurrence after three major types of treatment the ablation the partial nephrectomy and the radical nephrectomy so follow-up frequency these are things that we have to do such as history and physical it's not all about imaging so we have to actually talk to our patient we have to listen to our patient we have to examine our patient blood work has to be done imaging of the chest because that's the most common place for the cancer to go to outside of the kidney and abdominal imaging of course i'm going to focus only in the abdominal imaging for this part because that's what i'm assigned to do as far as the local recurrence so this is what we what the national cancer comprehensive cancer network guidelines say for ablation and these are generally for stage one a tumor meaning tumor less than four centimeter so in general they recommend abdominal imaging with either a CT or MRI about three to six months after the ablation and then yearly after that for up to five years these are low aggressive tumors in general as far as follow-up after surgery for stage one and this could be partial nephrectomy or radical nephrectomy and as you can tell here there is a difference between the partial and the radical because with the partial we still have remainder of the kidney to look at as well to make sure the cancer doesn't recur in that same kidney that we're operating on and you could see here the follow-up is initially about three to 12 months after the operation and then yearly for three years afterwards for the partial and for the radical it's three to 12 months after the initial surgery and then afterwards it's per clinician discretion and this is only for stage one that I'm showing here now for stage two and three which have a higher chance of recurrence this is what the guidelines recommend three to six months after the operation and then every three to six months for three years and then yearly for a couple more years and then per discretion of the clinician and the patient and again you will see different guidelines saying something differently there's no one right way to do it so what about recurrence after ablation therapy this is a patient a 60 year old gentleman that had a few comorbidities so their doctor their doctors basically decided to do ablation however after the ablation was done several months later he had a recurrence it was observed for a little while kept on growing so the patient then came to our hospital for additional care you could see this is how normal kidney will look like this is the kidney that has the tumor over here and I'll show you what happened at the end of this part so in general ablation recurrences are quite rare and they are rare because now we have learned which patients we should do ablation for and which patients don't need ablation because our success rate will be not good so the recurrence rate should be really less than five to ten percent and that's what we discussed with our patients and when we do have a recurrence after ablation it's all the options are available so we can either observe we can do ablation again or we can do surgery and it all really depends on what the initial tumor was what is the size of the tumor right now after recurrence and what is the performance status of the patient and how healthy the patient is and how aggressive does the patient want us to pursue the tumor this is from the national cancer institute and they have great experience with very aggressive tumors such as VHL tumors that are multiple as you could see here a small number of studies and this is going to be a recurrent theme only 13 patients were treated all had a partial nephrectomy after failure of ablation therapy multiple tumors were removed from the kidney and this is typical for our patients with VHL surgery is a long operation for this patient group was about eight hours with you know a reasonably high blood loss for patients who don't have genetic syndromes usually we have to deal with one or two tumors that recur this is from our colleagues at the Cleveland Clinic they looked at 27 patients nine had ablation failure and 18 had cryoablation failure and you could see here that patients were treated differently not everybody got the same treatment so 14 patients had a partial 12 had radical and one had a surgery that was aborted and it's important to know why this patient had an aborted surgery it's because the discussion between the surgeons at the Cleveland Clinic and this patient before the operation was you have one kidney you have a recurrence in that kidney if i cannot remove this recurrence with an operation what do you want me to do do you want me to take the entire kidney and you'll be on dialysis or you want me to stop the surgery and the wishes of the patients were i don't want to be on dialysis if you cannot remove the tumor leave it there and that's why it's important to have these discussions before an operation and not have to come talk to the patient's family during the surgery and try to assume that the patient's family knows what the patient would want so you have to be very upfront when we're talking with our patients with these operations the tumor sizes are small the blood loss is you know with an acceptable limits the complication rates are higher when we're doing operation the second time and that's normal because the first time the surgery is done our body is healed by forming scar tissue so when we go back again to do another operation we have to fight with the scar tissue and that increases the complication rates when we're doing the treatments for our patients and as you can see here the recurrences were actually very good as far as the number were very low so only eight percent of patients had a recurrence and you have to keep in mind that here we're treating a recurrence from a small tumor that originally took place so if you had a very small tumor initially and you had treatment and you had the recurrence most of the time the recurrence will not be very aggressive but of course each patient will have an individual case scenario this is our experience we looked at 14 patients again another small study 10 had ablation failure from radio frequency and 4 had cryoablation failure and you see the same theme here that most of the rescue or surgeries were done about two years after the original operation so this is a very recurrent theme that most of the secondary operations happen about one and a half years to two and a half years after the original operation most of these patients had the partial nephrectomy the rest had radical nephrectomy the age of surgery was about 65 years which is the expected age surgery in general takes longer when we're doing it the second time around and the tumor size is still small it's still about three centimeters so just a little over an inch and we did have major complications in four patients but fortunately all the patients recovered from these complications and one recurrence only was noted and this is an inpatient with VHL again which is not an uncommon scenario this is the patient that I showed you earlier we did an open partial nephrectomy for this patient and the good news is that you know we really no bridges were burned I would say because this still was a stage one tumor of course we would have preferred to do the operation for the first time and be done with it and not have to subject the patient to another procedure but this is what happened with this patient and ultimately was found to have a low grade low stage tumor with clean margins and the patient currently is doing well after the operation so the first part was recurrence after the ablation therapy this part will be recurrence after a partial nephrectomy so part of the kidney is still there and let's see what happens with these patients this is a 79 year old gentleman who had an open partial nephrectomy at another hospital and then after follow-up was found to have a recurrent tumor this is normal kidney down here and this is the tumor over here and the tumor was noted to go to the renal vein as well and you've heard a lecture on that earlier today and i'll show you what we did for this patient later on again thankfully the local recurrence rate after a partial nephrectomy if done appropriately should be low it should be less than five percent and the location could be either in the kidney itself that we've already operating on it could be in the same location where the tumor was removed or it could be in another location of the same kidney or it could be around the kidney which is something I will discuss a little bit later this is the Mayo Clinic experience and these patients basically had an initial partial nephrectomy they had a recurrence and the way these patients were salvaged as far as treating their recurrence is by doing ablation procedure so as you could see we can if we have a failure of ablation we can rescue by an operation partial nephrectomy and vice versa sometimes we have failure of the partial nephrectomy surgery and we can rescue that with either an operation such as partial nephrectomy or radical nephrectomy or with ablation so the key as Dr. Schuck mentioned earlier today is not to have one tool when you're treating your patient you have to have a whole bunch of tools and you have to use each tool differently for each patient condition so it's important when you're getting treatment to go to a location that can offer multiple options not just one option and this is the outcomes from the Mayo Clinic study as you could see small number a small size of tumor major complication rate is actually very low and with an acceptable limit the recurrence rate is acceptable it's about nine percent so we can successfully rescue patients after failed partial nephrectomy with another procedure this is from the NCI group again showing you that these patients generally the patients that are treated and the NCI have VHL or other syndromes so the surgeries are usually longer they're much more complicated surgeries because these patients have multiple operations and have much more complicated clinical course the major complication rate here is close to 20% and the follow-up time at about five years the 20% of patients had another recurrence that needed another procedure this is our experience that we just published this year these are 44 patients who had a local recurrence after partial nephrectomy and as you could see here the stages at the initial partial nephrectomy as expected about two-thirds of the patients had stage one cancers and most patients had the clear-cell type and these are the types of curves you've been seeing all day they will call the Kaplan-Meier curves usually the lower the curve is the worse the outcome so the upper curves are patients who do better the lower curve is the patient who doesn't do as well so what we found and all these make clinical sense if you have a positive margin when you do a partial nephrectomy you have a higher rate of recurrence and that makes sense if you leave tumor behind the tumor is more likely to come back similarly if you had a more complicated tumor meaning larger deeper tumor you have a higher rate of recurrence if you have more than one tumor it makes the surgery more complicated so you have a higher rate of recurrence and if you have a higher stage tumor of course the risk of recurrence in that same kidney becomes higher and if you have a solitary kidney we're trying to do our best to save that kidney and prevent dialysis so we do much more aggressive surgeries on tumors that otherwise we would have removed the entire kidney so the rate of recurrence really becomes higher and when we look at all these factors together and multivariable analysis just putting them all together in the same mathematical formula all these were significantly associated with an increased risk of recurrence after a partial nephrectomy and as you can see again the time between the actual surgery the initial one and the recurrence is about two years and this is kind of a rough average of when we see these recurrences but of course there's a range of these recurrences they don't all happen at the same time but this is the average time when we do see them and again you see that these patients had multiple different types of surgeries again to show you that we have to look at each patient individually and offer what we think is the best treatment for this particular patient and the surgeries are still a little bit more complicated about two and a half hours of surgery blood loss is a little bit more and the pathology as you could tell here most of these patients were T1 which is a low stage tumor but we did see stage three tumors either T3a or T3b in this patient so again the pathology will vary in these patients this patient that I showed you earlier underwent a radical nephrectomy meaning the entire kidney was removed and the patients currently doing well about three years after the original surgery so again these surgeries are doable but they're more complicated and the patients need to be made aware of that fact so that they can be ready for the operation and the post-operative course as well and finally the recurrence after radical nephrectomy this is a patient that had surgery at another hospital they the patient had their hand assisted laparoscopic nephrectomy the left kidney is gone but you see a little bit of tumor here close to the spleen you see some tumor here close to the artery back on the on the musculature in the back and basically a lot of tumors were the kidney used to be and this is a recurrence that we see after radical nephrectomy again the good news is that this is uncommon so we don't see this very often and this is one of the earlier studies that looked at this this is from California just looking at 11 patients there was two post-operative deaths two patients actually died of cancer within two years of the operation the the reason I'm showing you this is that we've made a lot of progress as a community of urologists and medical oncologists over the years in treating our patients with a local recurrence so now the outcomes are much better this is also from about 20 years ago 16 patients and 15 patients had a complete resection and six patients were actually free of cancer without any additional therapy this is from over 20 years ago this is from our Mayo Clinic colleagues again these are graphs similar to what Dr. Speese just showed you that if you do have surgery for a local recurrence you do better than if you don't have any surgery but you always have to keep in mind that a lot of selection has gone into this type of treatment we can't operate on everybody who comes in with a local recurrence so we have to pick which patients we think are going to benefit the most from this type of aggressive surgery this is our experience that we published a couple years ago and Dr. Speese mentioned some of these data already again this is an experience of about 25 years and we only had 102 patients so this is a rare phenomenon and that's why when somebody's getting treatment for this type of situation it's important to get it done at a tertiary referral center and it's something I'll mention in my conclusion slide as well most of the patients had surgery done at other institutions but about 16 percent were done at our own institution and then they had a recurrence the time again from the initial surgery to the recurrence was about a year and a half and it's a little bit shorter because generally the patients who had radical nephrectomy had more aggressive tumors higher-stage tumors so the recurrences will happen a little bit earlier than those for smaller and less aggressive tumors and you know typical study group as far as the age is about 55 years so on the younger side most of the patients had an original surgery that was done in an open fashion as expected most patients have high-stage tumors so aggressive tumors about 20 percent actually have positive lymph nodes at that time and about 13 percent had positive margins at the original operation as you could see here the areas of recurrence can vary but all of these are considered to be local recurrence so it could be either where the kidney used to live we call that the renal fossa it could or it could be the lymph nose around the kidney or the adrenal gland if it was left behind and we do leave the adrenal gland behind on purpose and most of our patients if it's not involved so it's not wrong to leave the adrenal gland on the same side and as you could see here about half the patients had symptoms so these were not detected by imaging these were detected because because the patient complained of something and they went to their doctor and they had an evaluation that showed what the problem was the recurrences are a little bit on the larger side here it's about close to two inches we performed open surgery in the vast majority of these patients we had about 15 percent complication rate so these are serious operations with a serious blood loss as well and the surgery takes about three and a half hours or so on average with a hospital stay of about a week and this is an important point that we discussed with all of our patients right now so about 60 percent of the patients that we operated on had a relapse after the operation but the good thing is that the time for that second relapse was about two years later and the survival from that time was about five and a half years so just because the patient has a recurrence it doesn't mean that that's the end of it there's still patients that we can salvage with surgery and with medical therapy as well and these are the predictors of the patients who will do worse after the local recurrence surgery basically patients with positive lymph nodes at the time of the original operation and patients with a larger size of the recurrence and that's why it's important to detect the recurrence when it's more on the smaller size and not basically a very large recurrence that it becomes very hard to treat and to cure the patient from and these are some studies as well that you know Dr. Spies and colleagues have worked very hard to put together but 50 patients from four major centers again these are patients who had an isolated lymph node recurrence close to the kidney area and you can do surgery as well in the situation but about half the patients will have a recurrence again we can potentially cure about 40 to 50 percent of patients who have an isolated recurrence after an aggressive initial surgery and just for the sake of time i'm going to talk about the recurrence of the IVC thrombus and this is a very very difficult situation and our colleagues at the Mayo Clinic looked at this and unfortunately all the patients that had this recurrence and had surgery did not survive past a year again indicating a very aggressive recurrence that surgery has limited benefit in this situation there are some small reports about doing radiation after recurrence of a thrombus and our colleagues at UT Southwestern and Dallas have worked on this and they have an ongoing clinical trial for this as well and this is what we did for this patient so this is basically a surgery that we do with colleagues from other surgical specialties such as surgical oncologist so we had to remove all of these things in order to remove all the tumors that were sprinkled after the initial surgery and this patient is currently doing well about two years after the operation and again this is not a one person surgery this is a surgery that we have to collaborate with other surgeons in our hospital in order to make sure that we can do a complete operation to remove all the tumors that we can see in the safest way possible so take home messages the good news is that local recurrences are rare but they definitely can happen we should do surgical resection in patients who have a good performance status and for the outcomes as far as recurrences after ablation or partial nephrectomy are good so most of these patients can be cured if we do surgery after the ablation or partial nephrectomy failure if we have a recurrence after radical nephrectomy these are generally more aggressive tumors so potentially we can hear about 40% of our patients in this fashion it's very important to follow up with your doctor after the initial procedure it's not you know you have a surgery and then that's it if there is cancer on the pathology follow up is mandatory afterwards and the best outcomes for a patient to have a local recurrence are in patients who have low comorbidities meaning they're generally healthy they have a good performance status the best outcomes are in those patients who don't have distant metastatic disease meaning it's only an isolated local recurrence and the later the recurrence occurs the better the outcome is as you can imagine if you have a recurrence three months after the initial surgery that's usually a very aggressive tumor that's hard to cure but if the recurrence happens one or two or five years after surgery generally these are recurrences that have a better prognosis and it's very important to have this type of treatment for a local recurrence done at a tertiary center a center that has a lot of experience center that has a lot of different ways to treat the tumor not just with surgery but maybe with ablation with medical therapy and a lot of disciplines that will work together to try to find the best outcomes for the patients thank you for your attention