First up, thoracic radiologist Brett M. Elicker, MD, presents current guidelines on who will benefit from lung cancer screening; offers tips on discussing screening options with patients, who often worry about CT radiation exposure; and explains nodule features that qualify as “suspicious” (i.e., warrant referral). Next, thoracic surgeon Johannes Kratz, MD, describes state-of-the-art techniques for treating early-stage lung cancer, including neoadjuvant chemo and robotic surgery.
Happy to be here and talk about a topic that I think we all care about very deeply and have been very involved with over the last 10+ years since the National Lung Screening Trial came out, and my goal today is to start to introduce The concept of lung cancer screening, a little bit about the data behind it and some of the imaging, which really forms the core of, of making decisions in these patients, whether they'll follow a CT or do some more invasive procedure. And of course, this all started in 2011 with the publication of the National Lung Screening Trial, and since then, there's been a, you know, really, um, a huge effort to try to, um, uh, roll this out around the country. And um just to show you some of the inclusion criteria for the National Lung Screening Trial, um, and these criteria sort of form the crux of the type of patients that you want to refer to us. I have in parentheses also, the United States Preventive Task Force has sort of expanded the age and the pack years, um, smoking pack year history to a larger population. So, these are what's essentially approved in the US, but the Um, so, uh, the type of patients that should be referred for lung cancer screening at least should be considered are aged 50 to 80 years, 20 pack years or greater. This actually recently changed. It used to be 30. In the last couple of years, it's changed to 20. Current or former smoker quit within the past 15 years, and then clearly no signs or symptoms of lung cancer. If they have signs or symptoms of lung cancer, you should be doing a CT for diagnostic purposes. And also really important in that, and, and I think smoking cessation is actually really one of the critical things and one of the most important interventions in these patients beyond doing lung cancer screening. So, documenting that they understand, patients understand the risks and benefits of this, and offering smoking cessation is a core principle that we, uh, that is required as a part of this process. Just very briefly on the results of the national lung Screening Trial, again, which formed the data that forms, you know, the crux of why we do what we're doing. Um, they compared randomized patients to CT or chest X-ray and then compared those two groups of patients. Obviously, in CT the positive rate was a lot higher just because CT is much more sensitive for detecting pulmonary nodules. The lung cancer rate was a lot higher in the CT group. You can see the numbers here. A much lower rate of deaths, clearly because we're catching lung cancers at a much earlier and more treatable stage. And you can see that the relative reduction in lung cancer mortality was 20% for CT compared to chest x-ray, and overall reduction in mortality was around 7% or so. So, again, these are the results that have formed the basis of why we do lung cancer screening. That being said, I think there are quite a few challenges. I think, you know, there's still challenges in mammography, even though that's been around for many, many years, and we have some similar and different challenges in lung cancer screening. So, I wanted to talk about some of these challenges. I think these are particularly things that are important to patients and you need to have some understanding of them in order to discuss the risks and benefits of the procedure with the patients, but I think each one of these challenges also represents a real opportunity for improvement and maximizing the efficiency of lung cancer screening. Let's start with cost and particularly radiation, which many patients are very concerned about. From a cost perspective, this is a study looking at the cost of lung cancer screening. Screening programs in general, the threshold to screen, which is dollars um saved per or cost, cost of, uh, of the cost of screening for quality-adjusted life you're saved. $100,000 or less is generally considered the threshold below which we would want to screen. Lung cancer screening is around $81,000. So, it's below the threshold, still within the range of what we would recommend, although it's not a lot below the threshold. Some interesting things that came out of this study is that actually current smokers, it's much more efficient. And also, in women, it's much more efficient. So, we know what the, the, the criteria are for screening, and that doesn't really change based on this data, but we might want to recommend it even a little bit more strongly in patients who, where the cost is going to be, you know, of doing this is much more, is much more efficient than, than in, um in other patients. Interestingly, the, the sort of maximum cost benefit occurs in 60 to about 70 year olds. So, just some interesting data in general. I think perhaps more importantly is the radiation risk. And this, this is something that patients are very concerned about. I still remember back, I think it was about 10 years ago, there were two big papers that came out that talked about the dangers of chest CT and radiation, and patients then would come in and be very concerned about and still are. Um, I think that this is something that people are worried about, but it's much less concerning than we give it credit for. And I'll show you why that is in a second. The background radiation that we all get from living and breathing and walking around every year is 3 millisieverts, that's the total body dose. And I think, as opposed to comparing to a chest X-ray, um, most imaging modalities should be compared to the background, the yearly background radiation dose. A low-dose chest CT is essentially living for 3 to 4 months and getting a background radiation over that period of time. Interestingly, if you move to Denver, You get 2 more millisieverts a year, which is basically about 3 chest CTs. So, that kind of puts it into context. Um, the dose from a chest CT, a low-dose chest CT, is extremely low and really is a small percentage compared to background radiation. OK, great. That's radiation and cost. Let's talk about perhaps the most difficult challenge, which is false positives. In the lung, national lung screening trial, over a quarter of the positive studies were sorry, of the CTs were positive, and those were classified as nodules 4 millimeters or greater. Of those, almost all were false positives and only a small percentage, around 4 to 5%, were lung cancer. That sounds horrible, right? That sounds terrible, but that being said, the majority of false positives simply got imaging follow-up and did not get invasive procedures. And in fact, the, of the positive studies, only about 10% of those patients got invasive procedures. So, while there are many, many false positives, the majority of those just get imaging follow-up. And I think this is where a multidisciplinary approach is really critical. Um, patients come to us, I think for, for simple, small nodules, we follow those, those are pretty easy to understand. But for anything more complex to that, I think it really helps to have a team of dedicated thoracic radiologists, thoracic surgeons with experience in this area, pulmonary medicine, thoracic oncology, and I think by Presenting patients in like a tumor board, particularly early on, um, this is going to really maximize treatment and minimize the harms to a patient. So, I think this is one reason. I think it's really good to have a group together, all with, all who are experts in this area. Um, as after the National Lung Screening Shot was, um, published, the lung rads was developed, and you probably are familiar with a lot of the ACR has put together a lot of Uh, RADs. You know, there's, there's BIRADs for breast imaging, there's TRADs or thyADs for thyroid imaging. There's also lung RADs. And, um, this allows us, and this is actually a much more, this is a very simplified version of it. There's, there's more complicated charts based on this, but this gives you a sense of the different lung rats categories. In particular, the ones that we're most concerned about are going to be the ones that are suspicious. And in lung rats, only about 4% of patients are going to be in that suspicious category, and these are patients where some kind of immediate evaluation, whether that's PEET or invasive procedures like tissue sampling or, or surgery are considered. So, it's a fairly small percentage of patients who get screened. Interesting when you, when you go back and look at lung rads, if it had been applied to the original national lung Screening Trial criteria, there's some interesting results. Basically, the positive rate goes down quite a bit using lung rads as opposed to the National Lung Screening Trial criteria. So, we're reducing the false positive rates on both the baseline and the subsequent CT. So, that's one real advantage of using lung rads is that we have a much lower rate of false pos positive, positive studies actually. Uh, the sensitivity of lung rats is a bit lower, but probably in many of those are these more indolent, slow-growing, uh, lung cancers, which may not be as important to treat. OK, great. In general, there is lung rats, but in general, this is the role of CT and the evaluation of nodules, and I think, you know, no matter what specialty you're in, you know, this is a primary care presentation, but no matter what specialty you're in, if you ever order a chest CT or a chest X-ray for that matter, you're gonna see nodules and you're gonna need to know how to deal with them and how to discuss them with patients. So, there's basically 3 categories of nodules. We can put in, uh, every nodule can be put into one of three categories, do nothing. Follow up with CT where the risk of malignancy is low but not close to zero, and then some immediate action where it's more concerning. Um, do nothing is benign features, definitively benign features. That includes benign patterns of calcification, presence of fat, um, subpleural lymph nodes of a typical morphology, long-term stability, or younger patients who are not going to get screened to begin with, but you may get a chest X-ray or a CT in a younger patient who has a nodule. And this is just showing you some of the definitively benign features. Again, benign patterns of calcification, presence of fat, the typical lymph nodes, which are sort of triangular and subpleural, and then long-term stability, meaning at least 2 years with a solid nodule. So, just to give you a sense of the definitively benign features where no additional imaging or follow-up is required. The majority of patients, however, fall into this kind of intermediate to high-risk categories, and perhaps size is one of the most important things that we look at. And usually small nodules in a patient who's not at high risk, we do nothing, but most of these other nodules we're going to follow, and I think size is one of the most critical things in determining the likelihood of malignancy. And again, I think that if you see a patient who has a lung nodule, you should be thinking about it. They're gonna ask you, I have a spot on my lung, doc, you know, what is this cancer? Is this something else? And the majority are going to be benign, and I think again, size is one of the critical determinants. of the likelihood of benign versus malignant. You can see in this study, which, which grouped nodules by size and showed the percentage of nodules of those sizes that were malignant, less than 8 millimeters of all the nodules or less than 8 millimeters, 1% or fewer were malignant. Whereas at 8 millimeter cutoff, that's where the risk of malignancy started to go up and really above 20 millimeters when it, when it was quite high. So, size is critically important. Uh, there are other things that, other features we look at besides size. Perhaps the most important is going to be spiculation. Spiculation is these sort of thin lines that radiate out from the center of the nodule, and there's, um, the, it's, it's, if you see that feature, somewhere around 60 to 90% of nodules with spiculation will be cancer. This is a nice example of an adenocarcinoma with a very typical linear, uh, radiating kind of corona of lines radiating out from the center of the nodule. Not only that, these tend to behave more poorly. They have a higher risk of lymphatic and vascular invasion, so they tend to metastasize somewhat earlier than many of the other lung cancers. That being said, we occasionally see this with granulomas disease. This is a patient who had a normal chest X-ray 3 months and then a lung cancer screening CT with a new nodule essentially came over, came on too quickly, looked spiculated, decided to follow it, and that went away. So, again, speculation is really important. And then, um, and then growth is really important too, right? I think perhaps the most important thing that we do in that multidisciplinary tumor board where we're discussing patients is take patients who might have gotten invasive procedures and decide maybe we should just follow them with CT. So, I think the two critical things in determining is a nodule likely benign or malignant is size and whether it's growing. Those are the two critical things. And here's a nice example of a nodule. That we found at the VA hospital that I also work at, seen on multiple scans in a row over two years. And at any point in time, that nodule would probably has a low risk of being malignant. If you see it in isolation. But when you see it all in a row and see that it's consistently growing on multiple scans in a row, then all of a sudden it becomes very concerning. This, this nodule was resected and this was an adenocarcinoma. Almost all cancers that are solid, and we'll talk about the difference between solid and sub-solid cancers in a second, but all the, most all the cancers that are solid have a doubling time of less than 1 year, and that's actually kind of a good rule to remember. OK. Challenge number 3, we only have a couple more challenges left, detection of indolent neoplasms. Now, we all know that one of the downsides of screening is that we may find cancers that would never cause the patient problems. Cancers that they would die with, not die of. And so, uh, this has actually been studied in lung cancer patients and they found that the overdiagnosis rate in general was just under 20%, which is a, a relatively high, but reasonably low number. And that's was particularly common what we call bronchoalveolar carcinomas and we'll talk about what those are in a second. Again, I think this is just important to understand, to put, put what your patient's results of their CTs are in context. Here are two nodules. You can see they appear quite different. One is what we consider a solid nodule. It's very dense, very white. This is what I would consider on the other side of the screen, a ground glass nodule, which is much less dense. Now, first of all, there's multiple different features we can determine to determine the likelihood of these being malignant. But based on density and size alone, this nodule on the left has about a 15% chance of being cancer. This nodule on the right has about a 70% chance of being cancer. Ground glass nodules that are persistent at least 3 months apart have a much higher risk of being a neoplasm, but they tend to be very indolent, slow-growing neoplasms that may never cause the patient problems. So, we tend to be much more conservative with nodules of this density or attenuation, and we tend to follow them over time as opposed to doing invasive procedures. And this looks like graham glass because it's a typical lipidic growth. Lipitic growth is non-invasive growth. The tumor kind of creeps along the surfaces of the adler septal walls, but does not actually invade underlying the, the lung parenchyma. It's pre-invasive, just like ductal carcinoma in situ in the breast. It's pre-invasive and eventually may turn into an invasive ductal carcinoma. Whereas this actually did turn out to be a cancer on the left side of the screen, even though it had a relatively low risk, we biopsied this and it was came back an adenocarcinoma, and this just had invasive solid growth. So, these are the cancers, the ground glass nodules are cancers that tend to behave in a much more indolent fashion. And so, what we tend to do with these can these cancers or neoplasms is follow them over time and wait for them to start to grow more quickly or develop solid components. And then that, that sort of suggests that they're becoming more aggressive. OK, another big one is limiting extra tests in the last 5 minutes or so. Lung rads, most of the patients in lung rads will get follow-up CT or just routine screening. The other group of patients either get follow-up CT at a 3 or 6-month interval, P PET CT or tissue sampling, which may be a biopsy or, um, or surgery to do a definitive treatment. So, we're talking mainly about these more suspicious nodules, which are larger, more quickly growing, or have specific suspicious features like siculation. PET CT can be very helpful in pushing patients to the lower or higher category in patients who have nodules that are kind of in between in their suspicion for malignancy. So, here we have a small nodule, an intermediate-sized nodule, and a big ugly spiculated nodule. And I would say that the one on the left probably is not cancer, the one on the right probably is cancer, and the one in the middle, it's kind of a toss-up, it's fifty-fifty. And I think that's really where PET CT is very helpful. You know, with a low, if the nodule is unlikely to be cancer, we're going to follow it. If the follow is likely to be cancer, we're going to do some immediate intervention, surgery, biopsy. It's really these in-between nodules that are more difficult, and I find PET CT can be very helpful in kind of uh triaging them to, if it's PET negative, you follow it with CT. If it's PET positive, then you do some immediate evaluation like surgery or biopsy. So, that's the use of PEET, but actually, the main use of PET is really for staging. It's really important to know some of the limitations of PET. There are a variety of different false negatives. Uh, it tends to occur with smaller lesions. So, I showed you this one already. This was that nodule that was small, but consistently growing on multiple scans in a row. So, that was suspicious because it was growing relatively quickly, even though it was a small nodule. A nodule that's less than 8 millimeters is very sorry, I should say a cancer that is less than 8 millimeters is very commonly PET negative. So, you wouldn't believe a negative result in a nodule that was small and you were still suspicious about it. The other thing that PET's often negative is, is, is these indolent tumors, neoplasms, that present as less dense nodules, these ground glass nodules. So, this is a, this patient had this ground glass nodule. It was slowly growing over about a couple of years. They wanted to get surgery. The patient really wanted to know what it was. The PET was done, it was negative. I don't care. That's still a neoplasm because I know these indolent neoplasms often don't have a lot of FTG avidity. Also remember, so here are the, here's the common causes of false negative PETs. Also, remember there are a variety of different false positives, the most common of which are granulomatous diseases, either granulommas infections. This is a patient with coccy who had a granulomas infection, had acute onset of fever and white count and cough, so the clinical scenario wasn't suggestive of malignancy. They got a PET, they got a workup, they got a biopsy. Everyone was worried they had cancer, they had coccy. Uh, the other one, big one is sarcoid. So, if you have any sarcoid patients, those tend to be quite FTG avid. So, just putting the PET in context and knowing the false, negatives and positives, but in the majority of cases, PET is quite accurate in making this distinction, but really the main role of PEET is to do staging before, before doing surgery and to look for lymph node and distant metastases. I will finish up and then turn it over to uh Doctor Kratz to say that now we're sort of, now that you have a foundation and understanding, detection of nodules, determining the likelihood of malignancy and how that determines what happens next, right? If, if a nodule is a low likelihood of being malignant, we do CT follow-up. The nodule has a high likelihood of being malignant, we do PET followed by biopsy, surgery, some sort of invasive procedure. The question is when do we do those procedures and Doctor Kratz is gonna talk more about this, but these are some guidelines on it. If there's a less than 10% likelihood of a nodule being malignant, CT follow-up. If there's a great 7% chance of being malignant, we go right to surgery. Why? Because if you did a biopsy, you wouldn't believe it since there's such a high pretest probability of malignancy. A negative biopsy doesn't really exclude cancer, so we go right to the definitive treatment in this large gray area in between, between 1010 to 70% chance, pretest probability of malignancy. We would probably do a biopsy through a variety of means, whether CT guided or bronchoscopic guided for further management. Um, and Doctor Kratz will talk more about this in a second. So, hopefully, uh, 01 last logistical challenge in the last couple of minutes. Setting up a lung cancer screening program is really challenging and from a logistical standpoint. One, you gotta really make sure that these patients are candidates and that's really on you and to help us in that regard. Know the criteria for lung cancer screening, 50 to 80 years old, 20 pack years or greater, current smoker or quit within the last 15 years. Patient could get treatment for lung cancer whether that's surgery or SBRT CyberKnife, and you've done shared decision making and have offered them smoking cessation. All of those are critical to ensuring these patients are candidates. We send all of our data to the American College of Radiology, which, which we, this is our problem. We have a huge IT infrastructure to do that. And then, of course, it's really important to ensure patients get appropriate follow-up, whether that's CT follow-up, PET, other invasive procedures, and that also requires a significant infrastructure investment. So, with that, hopefully, I've sort of set the stage for how we approach lung nodules on imaging and this next steps. And now, I'm gonna turn it over to the person who is gonna be in charge of doing surgical resection in these patients, and, um, so that's Doctor Kratz. So, uh, and then I look forward to your questions at the end. Thanks so much, Britt. Um, hopefully everyone can hear me and see my slides, OK. Someone please tell me if I can't. Um, so thanks so much, Brett, for that, uh, outstanding introduction. Um, you know, it's, it's really nice to see how things are laid out from an imager's perspective. I also, in full disclosure, my wife is actually a primary care physician and his internal medicine trained, so I actually asked her and I said, if I'm talking about this topic, what do you want to know? And one of the things, besides the numerous things she actually mentioned that Brett already covered in his talk was, um, was when to refer and then what do I need to refer. So I'm actually gonna start my talk with those very things. And so, just to try to simplify things, I know that, you know, we, you already saw this lung rats criteria here, and the point is not to really memorize or to even worry about what this table uh says here. They're actually very, very complex as Brett mentioned. Um, but what you really want to look out for is the word suspicious. So suspicious always warrants a referral. We don't care, uh, on our end if that, uh, lung nodule hasn't had any prior imaging. We don't care if, uh, it hasn't had a biopsy. We don't care if someone else hasn't evaluated. If it says suspicious, that actually warrants a referral to me, interventional pulmonology, um, our group in general. And, you know, these suspicious can, can either be in the eyes of the radiologist. At UCSF we use the lung rads guidelines, um, but, um, they can also just be suspicious if you're looking at a community CT scan or you get an outside read and they're not using the lung rad guidelines. Whenever you see that word, it's OK to refer and we encourage those referrals. If you don't see that, uh, word, sometimes you will see other language. The size is greater than 6 millimeters and you see a report of growth over time. That actually is worrisome and, and suspicious. Or if it's just a high-risk patient and there's a nodule that's greater than 6 millimeters, we also encourage those kinds of referrals. So, somebody who is very worried because they have a family history, somebody who has an extensive smoking history, advanced age, etc. So, if you or the patient is suspicious, again, just from a referring provider standpoint or, you know, seeing these referrals, we always welcome those kinds of investigations. Don't think you need to work up these patients very thoroughly, uh, before referring them to us. And then what do I need to refer? Basically, just a chest CT. Brent already talked about a biopsy. There are various ways to do them. Um, there is a CT guided biopsy, there's EBS, there's EMN guided biopsies, there's surgical biopsies, but they're not really necessary in order to get that patient seen by us. Um, again, he already went over the scenario that if we're really clinically suspicious, we're not gonna act very differently whether the biopsy is negative or positive. Unfortunately, biopsies are about only 60% accurate in the lung, um, which seems low, but it also, also makes a lot of sense when you think that the lung is mostly comprised of air, so it's a fairly difficult part of the body to biopsy. A PET CT, some people ask us about, it is helpful. Sometimes insurance won't cover it. If a patient is not already diagnosed with cancer, so if you just have a solitary lung nodule, even though it helps us make decisions, sometimes we'll order them and the insurance company won't cover them. So I would say don't, don't worry about it, quite honestly. Again, if you have a reason to refer, just refer the patient to us and we'll take care of the rest. So I'm gonna actually switch gears and try to give you information in a different way just through a case presentation. Um, I think this is most relatable about, you know, what happens to a patient when you refer them to us with or without a diagnosis of lung cancer. I picked one that has a diagnosis of lung cancer because obviously they go to surgery and that's my area of specialty. So we'll just switch gears for a second and focus on Mr. Yi, a 68-year-old actually who met the criteria for lung cancer screening that Brett already reviewed, 40-pack year smoking history, quit within 15 years, uh, and age 50 to 80, here 68 years old. Otherwise, was very healthy, worked as a beekeeper, true story, in, uh, California. Uh, would have a friend and bred as a citrus grower, I presume. And hopefully you can see this video plane. If you can't, so there is a nodule that's quite obvious here, it's about 1.7 centimeters, a spiculated right upper lobe nodule, and that patient was referred to us. So what happens at that point? Well, all these patients actually get, uh, presented at our UCSF tumor board. Uh, there's a variety of colleagues that sit on this. Uh, so Doctor Eliker participates or his radiology colleagues. We have medical oncologists, pathologists, and so forth. These are pretty standard tumor boards, but you have some of the best experts in the, in the, in the world and all of these fields sort of weigh in on the, uh, best next steps for these patients. Um, this is where decisions about biopsy versus not biopsy. Uh, suspicious for cancer, not suspicious for cancer, and also discussion of clinical trials. And so we have a couple of open neoadjuvant trials here at UCSF, ones that are targeted at EGFR therapy. There are immunotherapy trials to consider, etc. So for Mr. Y he was presented, he had a pretty routine lesion. We are very suspicious. We decided to proceed with surgery. So I'll tell you a little bit about what kind of surgery, um, that he gets at UCSF. Obviously, we try to be cutting edge, we're minimally invasive, but we also do a lot of robotic surgery, and I've had patients ask me this question. They think robots and they think, uh, basically auto, you know, uh, automatic things like automatic surgeons. Um, that's not quite how it is. It's not like a self-driving car. I wish there were a, a go button and a stop button on the robot. And I showed this up here in jest, but I've actually got asked this question before that what exactly do I do if the robot's doing the surgery. So, unfortunately, um, I still have to do a lot. There's nothing automatic about surgery. And all robotic surgery really means is that we put a computer in between us and the instruments that we're holding. So this is traditional minimally invasive surgery where we're holding long skinny instruments that fit through small incisions in the patient, and all we're doing here is we're actually replacing us at the bedside. Holding those instruments with a robot that then holds those instruments, here's an assistant loading an instrument into the robot, and I sit at a console very nearby, and I basically control these instruments by moving my hands in space. And this is the genius of the technology and why inserting a computer in between our tools in our hands can sometimes really make a big difference. Sometimes it's more relatable to patients when I say in the old days, I used to make a large incision and then put my own hands inside your chest. Well, these days, I'm gonna do it by making little incisions, and I'll put little robotic hands inside your chest, and then I control the movement of those robotic hands in a very sophisticated fashion. So that often um makes the point, and why do we do things like this at UCSF? Well, this is our modern-day uh minimally invasive instrumentation kit that's non-robotic at UCSF and you can probably guess what it looked like in 1980, same picture. And if I showed you this picture of instruments that looks very similar to the ones that are Modern-day equipment, you may be surprised or may not to learn that that was drawn pre-Civil War in 1849. Uh, and so these kinds of instruments can only take us so far, they really haven't advanced that much, uh, because they're just long thinner versions and skinnier versions of what we use in open cases. Now you compare that with putting a computer in between our hands and the instrumentation that we're using inside a patient and we can do very sophisticated things. This is a famous, uh, video on YouTube of a da Vinci surgeon sewing a grape skin back on a grape, something of course that can never be done with that kind of precision when we didn't have robotic-assisted surgery. It often, uh, also opens up new paradigms and so there's a fancy camera on the robot that can do fluoroscopic guidance. So one of the things that we sometimes do is surgical biopsies and traditionally, lung nodules like this that are opaque are very, very difficult to feel in the operating room, but these days we've gotten around that by injecting these nodules. With a little bit of dye, and we can see that spot of dye in the lung very accurately. And what it allows us to do is do much more limited lung resection. So before we were taking out huge swaths of lung in the hope of getting these little lesions, now we can localize and know exactly where they are and only remove a small part of the lung. So we've been doing this at UCSF for quite a while. We actually did our first case, um, uh, almost 5, more than 5 years ago, excuse me, now, it was in 2016, and we quickly actually became the busiest robotic, uh, thoracic center that was in an academic setting in the western United States, so west of Colorado. We've also, of course, studied our outcomes and published these, uh, and showed better outcomes by focusing on robotic, especially versus open, uh, surgery, which we used to do for the more complex lung resections. So that's exactly what Mr. Yi received. He received this robotic-assisted right upper lobectomy, and you can see here, uh, this is just some of the anatomy. So this is the pulmonary artery that's supplying the lower lobe. This is a recurrent branch of the pulmonary artery, uh, supplying the upper lobe. There's There's a lymph node in between, a level 11 lymph node that's always very tricky to get out. And you can see how the wrist of instrumentation allows for a very precise dissection of this lymph node in a really nice procedure and a level of precision that we can never really get before with non-robotic instrumentation. Here's us completing the lobectomy in the middle panel, and then we're placing the lobe in the bag that contained his cancer. So it's been a really nice advance in thoracic surgery to allow us to do very complex operations that we typically only did open before in a minimally invasive fashion. So Mr. Yi did very well. He got his operation, robotic assisted lobectomy. He, uh, actually was doing well on the floor, uh, post-op day one. We don't send these patients to the ICU anymore. They don't have an epidural. They have minimal pain, and we get them out of the hospital on post-op day two, and here is his follow-up X-ray. One of the reasons we're able to do this is because at UCSF we focus on uh enhanced recovery after surgery. We're the 2nd academic center in the country. We actually do this in thoracic surgery specifically behind MD Anderson. Uh, and we showed previously, of course, because we're an academic institution that there is data to show that, um, we have decreased length of stay, decreased complications, and it's actually cheaper, uh, because we get patients out of the hospital faster. Uh, this doesn't matter from the patient experience, of course, but, um, it is a nice sort of benefit, uh, that shows improved care can come with improved efficiency as well. So what happened to Mr. Yi? Well, this is where most patients' stories end with early stage lung cancer, so they come back for their two-week post-op appointment. And he was doing well. He had a 1.6 centimeter lung adenocarcinoma, which is what the pathologist measured. He did have some visceral pleural invasion, but no negative lymph nodes. Because of this factor, he was actually staged at stage 1B. And I think in most other medical centers, I'd be uh estimating around 90, 95% of places, he probably just would have been observed. And he asks us, do I need anything else? And so here's where the NCCN guidelines come in, and again, this is not for you to worry about, but it is an illustration of how we think about things at UCSF. So there is this category that he falls into, Mr. Y, that puts him at high risk. Um, and so, he had, uh, negative margins and we can either observe him or give him chemotherapy, and if he's EGFR positive, you can give him a targeted agent if he's a high-risk patient. And the NCCN gives us some high-risk factors here that actually don't have a lot of evidence behind them. No randomized control trial evidence. They say poor differentiation, vascular invasion, wedge resection, tumors greater than 4 centimeters, visceral pleural involvement, unknown lymph node status. These are again, consensus guidelines, a bunch of very smart and talented people got together. Some of you may sit on these guidelines actually, uh, in, in committees, um, and put together sort of what our best practice is, but it doesn't always mean they have the best evidence behind them. So, it turns out there was very weak evidence for these criteria that determines that he had a high-risk, uh, tumor, and the decision is an important one, right? Because it determines whether he gets chemotherapy or not. So, you go over the evidence with him, you go over the guidelines, and he actually puts it back in your court and says, you're the doctor, what do you recommend? So I think that's where we do things a little bit differently at UCSF and obviously, we picked this case for a reason because this is not, uh, uh, you know, atypical for what we see. We actually developed a test at UCSF to try to answer this question with, uh, of what really determines a patient's risk for recurrence if they have stage one disease and they've had surgery for that. And so here you can see that this test was developed at UCSF and it basically gives the patient a risk score and ultimately a risk category. And as that patient risk score increases, their probability of mortality at 5 years, uh, increases as well. This was validated in two very large cohorts, so one at Kaiser, Northern California, uh, with stage one patients and also a very large cohort in China. It's the only, uh, uh, test in, uh, lung cancer that's available for early-stage disease, uh, that's actually been commercialized and available today on the market. And, um, it's the only one to have undergone this blinded international validation in two large cohorts. So you can see that the assay actually reliably discriminates a group of high-risk patients that have up to a 50% chance of mortality after resection of their quote unquote curable stage one disease. It also works in very, very small tumors, and so, you can see that uh there is this notion that tumors less than 2 centimeters are sort of safe, and that's exactly what Mr. Yi had, a tumor less than 2 centimeters, he had a complete surgical resection, which is why I say in most centers, probably nothing else would be done. It doesn't necessarily mean though if you have a small tumor that you're completely safe. Again, we see that this assay reliably identifies a group of high-risk uh tumors that cause mortality up to 5 years after resection of stage one disease. So, just to finish up his story, Miss Yi came back, Mr. Yi came back to the clinic. He was informed that he had high-risk disease per the classifier. And then he says, well, OK, now, now what? Will chemotherapy help? Now, we've been doing this at UCSF since 2012, and so here's our evidence that it will help actually. Um, so this is the 1st 250 patients we tested with this assay. And you can see that if the patients are low risk, and this is a prospective cohort now that's been followed since 2012. They actually do very well with the freedom from recurrence above 95%. Uh, they're very unlikely to recur after resection of their low-risk tumors. If patients are high risk, however, they have about a third of chance of recurring within 5 years after surgery. And the really nice thing about this is because we've been using this test to guide our adjuvant chemotherapy decisions, we've been giving those high-risk uh patients, uh, chemotherapy when they agree to it and the oncologists think they're a good candidate and you can see how that impacts their survival. They have survival on par with our low-risk patients. So Mr. Yi was represented at our tumor board. Um, he again had high-risk disease. He was referred to medical oncology. He got 4 cycles of carboplatin and Taxol, and currently he's doing very well without any evidence of recurrence. So, uh, I'm just gonna finish up here with a few slides on how to refer to us if you're interested in, in using our services. Um, again, if you find a, a lung nodule that's of interest, you can always turn that over to us if it's suspicious. You can always turn that over to, to Brett and I. We will take care of the patient from that point on. This is how to do it. You can always Google UCSF thoracic surgery. Um, here is the contact number, all of which you'll be given afterwards. If patients are far away, that's actually OK. We do so much now with, um, uh, you know, remote visits. That's one of the benefits of the pandemic. These patients can see us for their first time with video. Yeah, if they're entered into neoadjuvant therapy for some reason or they need that, they can also get that locally. They really only need to come to San Francisco for their surgery cause even their follow-ups now can be done, uh, virtually. Um, and if they need something else afterwards, adjuvant chemotherapy or even surveillance scans, it's very common for us to order them and then see these patients over video visits at 36, 12 months, and then annually for their follow-up as well. So a lot of this can be done remotely, uh, if your patients live far away. So thanks so much again for having us. This is, um, Brett and I are, of course, representatives of our tremendous team we have here at UCSF. When you're referring patients to UCSF, you're not referring them to me, but to this very talented team of people here. Uh, these are some of the surgeons, but of course, we have the radiologists, um, led by our chief of chest radiology, Doctor Eliker here, and there's a whole host of people, uh, who help, uh, manage all of these patients and manage the workflow and try to provide the best outcomes for our patients.
