In the first part of this grand rounds presentation, you’ll learn the best risk assessment tools for prostate cancer patients (avoiding past patterns of over- and under-treatment); the latest surgical techniques, such as fluorescence imaging and high-intensity focused ultrasound (as well as other types of ablation); and tests that allow for matching patients with appropriate options. The second part is an important look at past overuse of axillary lymph node dissection, with its lifelong consequences for many patients, and what the evidence shows about when this step can be avoided.
Good evening everyone and thanks for participating in our updates and surgical treatment options for prostate and breast cancer. Part of our cancer center ground rounds web series. I'm hoping to go breast medical oncologist here at UCSF. And this series was organized by laura Christina and myself. I'll let laura introduce herself and introduce you to the webinar. Hi, I'm Laura Crecido cmon VP of Cancer services at UCSF. So thank you everybody for joining us and we do this cancer center life series which happens four times a year. And at the end we'll go ahead and show you what our next upcoming one is. But thank you for joining us. Please look out for future events and tonight we have a really excellent lineup and we're really excited to have dr carol dr win and dr Alvarado here with us today. So I'll go ahead and um I think our first slide, I'm just gonna mention a couple of things for people on, there is a chat function but unless you're having trouble with the connection, don't use the chat function. There is actually however, at the bottom of your screen, A Q and a button there and by Q and A. You can put in questions which is great because then we will discuss them in the question and answer portion. So you can put them in as we're going along at any time. It's really helpful. Uh also we record this series. So you you can actually get a link for it afterwards if you want to share it with people or share it on twitter or other social media networks. So we really encourage you to ask questions and interact with us as we go along. Even in this zoom format laura I think our first slide is um just cancer center referral. And so we want to make sure and we will share this with you afterwards. Regina. Do you have that? You can put that up so we'll put that up at the end. How about let's just go ahead with um uh starting with Dr Peter Carroll who's going to be talking today about contemporary indications for radical prostatectomy. Can we make it a better operation? And dr Carroll is a urologic cancer surgeon at UCSF and um professor in the department of Urology as well as the Chair of Urology. Thank thank you both very much. Let me go ahead and share my screen here and we'll get get going. I'm gonna talk to you about surgery for prostate cancer. I want to point out at the beginning that here at UCSF the surgical program is part of a multidisciplinary program, a team of people, medical oncologists, radiation oncologists and we want to match the timing and type of treatment with the disease and patient preference. We have a very very large experience over time we record the outcomes of care, clinical health related quality of life. This allows us to educate ourselves and our patients very clearly about outcomes. This is linked to a large tissue registry where we develop and validate a lot of new technology And we strive to improve outcomes in patients selection continuously. I've probably done 5000 prostatectomy and I'd like to take back the 1st 4500 and do them all again. So the operation I do today is different than what I did last year, the year before and the ones next year I think we'll continue improve. So we make incremental improvements. The first lesson for us about surgery is who to treat. When I went into urology, the ideal patient for surgery were men with low grade, low volume disease? There was a lot of overtreatment. Any survival benefit was quite limited present. We see that high risk patients, higher grade, higher volume patients may benefit the most. We have more technology, Both biomarkers, imaging and a multimodal approach is common. So, here at UCSF we were big proponents of something called active surveillance. We felt that given widespread P. S. A. Testing, there's a lot of overtreatment detecting cancers that were too small to need treatment and yet commonly they're being treated. So, active surveillance was a response to the over detection brought about by widespread PS PSA testing. It's up taking the Urology community again, led largely by UCSF Hopkins in Toronto helped pave the way I think for an upgraded assessment by the task force on the early detection of prostate cancer. They recommended against in 2012. They reversed it and gave it a c recommendation most recently. This is our results. I'm showing you in 2200 men here treated on active surveillance. Active surveillance is PA. Testing testing of 3-6 month intervals, serial ultrasounds, Mri's and biopsy usually every two years or so. And this is 2200 men. But we're probably closer to 2500 and 2700 followed for a median of seven years. The overall upgrade free survival at seven years was was quite good at 41%. So 41% of men at 7, 10 years had really no change in cancer volume or grade. If you look at treatment, free survival was much better because a lot of the changes in volume are great were rather minor or marginal. And this says that for many men with low volume, low grade disease, you don't need to take him to surgery. You don't need to take take them to the radiation oncologists. They may be candidates for active surveillance. They avoid the morbidity of treatment. And even if patients get treated 7 to 10 years and still get cured, they avoid the side effects of treatment for a prolonged period of time. Uh there is a little bit different. So if you have a low grade tumor again, at least in grade 33, we consider low grade. They do a little bit better than those people with a little higher grade tumor. So the patients are active surveillance or again low volume, low grade cancers. And we've done a lot of work on this and published extensively the overall survival in our cohort. Again, out to 7 to 10 years of 96% prostate cancer specific survival is 99%. We have metastases survival of 99%. 1% of people develop metastases. Usually these people who are people who are not compliant with surveillance are men who choose surveillance despite having higher volume or higher grade disease busy table. It's I'm just showing you here there's a lot of ways to pick out the person who's more likely to upgrade. Again, older age, you know, it's counterintuitive but younger patients progress uh less rapidly than older patients. Something called P. S. A. Density P. S. A. Divided by the gland volume genomics M. R. I. When you use advanced technology, you're able to select patients for surveillance very, very well. Um now you'll hear from dr how in our effort to minimize morbidity, we have some patients with higher volume or higher grade disease which seem to be localized in one portion of prostate. And we'll see that we can actually maybe avoid whole gland treatment in a substantial number of patients and he'll talk about that. Now an addendum to this, although we have over treated low grade disease, lower disease. We have under treated high risk disease, high risk disease. These are men with higher grade, higher vine cancers are the ones who are most likely to benefit from treatment. This is work we've done now for many, many years. We were in a large cohort of men followed for for many years and we record the outcomes of care. It's a disease registry. It's done in 40 sites around the country. And what I'm showing you here is something called kappa score we've developed. It's actually a risk assessment tool. These men down here have low risk disease. In fact, in the U. S. Most men are are left sided in other countries where they don't do screening. You see more higher risk disease. And I'm showing the outcomes of surgery breaking therapy, external beam radiation therapy and surveillance. And if you look at prostate cancer specific mortality rates, uh there's really no difference in different types of treatment for low risk disease. But as you increase risk as a substantial benefit to surgery and higher risk disease. Now, when we saw this, this was a very rigorous study. We've done twice. Now. If not three times, we've control for all co variants demographics insurance, lots of different things. But it persisted. Surgery may best benefit those men with higher risk disease. Now, if you look at our cohort at UCSF over time, have we learned from this? These are patients who are treated in 2000 to 2020. The light blue are very low risk patients, medium kind of intermediate risk patients. And in the deep blue, higher risk patients. And we've seen how our treatment has changed over time. So again we've stopped applying this surgery. Two men with lowest disease. And increasingly now do it in men only those most likely to benefit. We still do see some patients with lower disease. These are generally men who have adverse genomics, maybe carry germline mutations. But the majority of our patients have clinically the disease. Now. Unfortunately this is not the case everywhere. We still see a lot of overtreatment uh certainly in the community and in many academic centers from open surgery to robotic. I'm one of the few surgeons that have done thousands open this is a prostate gland sitting down here. This is what it looks like. Open. Uh This is called the dorsal vein complex. And with a few surgeons of the transition from open to robotic. There is benefit to I think robotic surgery here. I'm this is a prostate over here. I'm dissecting this nerve bundle off the prostate which I think I think with robotic surgery patients recover quicker. And I think nerve preservation is better. Uh And we just showed that this is an M. R. I. Showing these nerve bundles down here in the postal lateral forces prostate. And here during surgery and we were doing this under 10 X. Magnification. We're preserving the nerve bundle along one side of the prostate very nicely. We're trying to minimize morbidity better imaging we think is critical for U. C. S. F. Uh and U. C. L. A. Lead the way to get FDA approval for something called PSM A pet PS. M. A. Is a surface molecule that is over expressed in the prostate and prostate tissue by 101,000 fold. Um With low expression and benign prostate and healthy tissues, 90% of tumors expressed PSM. A. Uh And this is revolutionized prostate cancer evaluation and care. So we've done we've gotten PSM a pet approved toM hope is a world leader here. But now we think that we would like to do inter operative imaging so we can use this P. S. M. A. S. M. A. Floor for developed by intuitive and how and I have worked with intuitive to look at for look at inter operative imaging. Um uh Now PSM is more sensitive than standard imaging is highly specific commonly changes management or recurrence. And we know that about 30 to 40% of patients who have lymph node metastases have them outside the standard fields for either surgery or radiation. So we think that intra operative imaging may allow us to better excise the prostate and do a a more therapeutic lymph node dissection. Uh and in men with high risk prostate cancer undergoing surgery. About 15 to 40% may have positive margins. You know when you took the tumor out, you saw a tumor at the edge or you missed metastatic disease, both of which impact outcomes. Uh And on our da Vinci robot, we have an advanced firefly camera. So we have a fluorescent camera. So what we're popularizing now is that I think the future radical prostatectomy is something called color coded surgery. This is what we do. We've completed a Phase one study where we give patients this PSM apec floor for intravenously a day ahead. We bring them to surgery. We do the surgery, we turn on the camera and we see the tumor flores including regional lymph nodes. Now this is a Phase one study done really for safety. It's very safe. We really had no side effects green urine as a side effect, which is transitory. And I'm showing you some inter operative pictures here and this is the prostate. Sitting down here and I turned on the camera it flores is um quite exciting to see that. I was not, I was kind of surprised to see these results. If we go ahead and here we're doing surgery and and I would have not noticed this but we see a small area of kind of in duration. This would have been missed. We turned on the floor of the camera, we see it that's positive. That was positive based on and this is probably one or two in size and pathology confirmed residual disease, excitingly. You know, we do see this in the lymph nodes here. I'm going to do a lymph node dissection along the left side of the prostate this, this lymph node flores. Isse. So we think we'll be able to test the hypothesis that lymph node dissection may be therapeutic using inter operative imaging. And here I'm going going ahead to remove that lymph node. I'm just showing you here the prostate along with the fluorescent images. They overlap very very well. You know here you see uh so called bread loaf of the prostate and we see this lights up quite quite nicely. We're quite excited by this weird discussions with the FDA Now for a Phase two trial which will be a national trial with along with three other centers. The U S F U C S F will be the lead. But I think this will be the future of radical prostatectomy. Not only will be allowed to excise the prostate better but we may be the limit uh the degree of dissection to patients will only benefit from it. So maybe we'll do more nerve sparing as we are able to assess margins. So in summary and I'm open to any questions here. Radical prostatectomy is an option possibly the preferred option for plenty of the significant significant multifocal disease and men in good health and long life expectancy. It's an evolving technique likely to be made more effective and less morbid with inter operative imaging for men was clinically significant but focal disease. How well talked about focal therapy ablation will may be a very good balance balance of the effectiveness of cancer therapy with more limited mobility compared to hold land radiation or surgery and one I want to thank. Thank you very much for listening. I could list a whole page of people who are part of this program but it's it's too much to get on one single slide and I hope I don't know if we want to take questions now if there are any or or or later. Yes. I mean I think that sorry for my laryngitis but um I think I don't have any questions in the Q. And a box. And remember if you can put the Q. And a box up it's great. But one of the questions that came up through chat, so just everybody's listening remember that if you can sending it to me is fine through chat too. But the question is with radical prostatectomy. There's still a lot of questions and concerns about toxicity right long term. And so what kinds of advances exists now about minimizing those side effects, nerve sparing etcetera. And does the robotic surgery help you with that or hurt you? It does not hurt at all. I think I think it helps because you have a higher magnification and the way you approach the prostate is more parallel to the prostate which allows you to set these nerve bundles off the the so we record these outcomes. The risk of incontinence. Uh UCSF is very very low, probably between three and 5%. It could be predicted based on patient age and measurement of the sphincter length which we do routinely on M. R. I. Right now, the big morbidity with surgery or radiation and there's really no difference. We have good long term data on radiation now is a change in sexual function. So if you remove already the prostate, the objective vine goes away, your libido remain intact. You have orgasms, directions. Now you can predict the likelihood of return of erections based on patient age, overall health and baseline function. And of course surgeon experience. But this is where you need to set patients expectations. So if a man has a core erections to begin with, they're not gonna be held by surgery. But if a man, I saw a patient today whose age early 50s, very good health baseline function uh very good imaging, he will likely do very well. But that's we spend the most time on. And and uh and then in fact any form of treatment for prostate cancer. That's a domain that could be effective. I think just letting for some patients is it's a it's an issue for others. It's not, we were just very clear to give them the UCSF data because we record these outcomes. So another question is um you know, how do you find the best surgeon? So if you are, you know going to have surgery for your prostate cancer. First of all, of course, you want to make sure that somebody, as you pointed out isn't just doing surgery without looking at your risk factors. So that's really important. But if you are thinking about a robotic prostatectomy, how many of the procedures does a surgeon have to have done for you to feel confident that they're going to do a good job and not something terrible. Well the more the better. So what what I what I say is one Uh you want to go to someone who's gonna listen to you and look at your data quite carefully. I always were. And I saw 22 patients today, me and them had seen other other surgeons who were the immediate response was to remove the prostate. And I said slow down, I think a lot of them may not need that. But I think you want someone who does this routinely. I mean that means weekly. And uh what I tell patients to ask is I I tell patients to ask the question as well. For men like you, what you want to ask your surgeons. For men like me, what can I expect with regard to cancer cure and side effects. And once you tell me that, tell me how you know that. Uh So here at UCSF we record this. So I did surgery on monday Tuesday. I do it tomorrow. I go back monday. I go back to Tuesday, but those patients will benefit from it because they have the risk features with that, that this would be a value. But you know it's hard to come up with a number. But you know the average surgeon doesn't do very many. But you want to go to someone who doesn't doesn't well records their outcomes and we can discuss it with you transparently. When do you look at outcomes for this kind of procedure? So when is the maximum toxicity? And do people get better if they have the toxicity? So the answer is yes. So so early on uh so about half the men gained control immediately. Usually they're pretty good control by 4-6 weeks time. It may take up to six months. Usually not. Usually it's early for urinary control. Usually it's early if urinary control persists it needs to be fixed. That's that's one of the problems we see in the often the community patients will have problems with continents and and it will never be addressed but it should be addressed I think by 6 to 9 months. Sexual function takes a little bit longer to improve. It tend to improve. Over the 1st, 2nd and 3rd year we record these continuously so we know each visit we get P. S. A. As we follow these long long long term and we have the funding to do it. A lot of our pages are interested in funding the program so we can track these outcomes. But yeah it gets better different than radiation with surgery. You'll see the problem and and it's early with radiation, we've seen a linear increase in the instance of of of side effects over time. Now again you can argue it's not a whole lot, but it's it's more significant to think with surgery. You tend to have the problem and you fix it. You tend you tend not not to have late effects. How do you fix it? If somebody has incontinence at six months, how are you thinking first? What we do early on 2 to 3 months. So we have for those who are interested in this, we have an app. It's free of the self is free on the apple um app store. It's called Kegel Nation. So and for men or women, you know, there's a lot of benefits to doing kegel. So one is we do kegel exercises if we think people are having trouble with it frequently going to a physical therapist early. So we're not seeing the improvement we want by six weeks we'll start having a physical therapist if you have incontinence that last longer that and is significant. Then it's usually a sling procedure or a sphincter procedure. Again, that that would be about one in 20 patients Interesting. Um so there's a question. Another question here and I know some of it is um you know, in various aspects but if somebody has a strong family history of prostate cancer. Um in this case a 37 year old whose grandfather and father both died to prostate cancer. What would you recommend to them for screening and anything else that they should do? And then as a corollary for that question. And I know again this is a little off topic of the surgery after you get diagnosed. But um do you do PS. A. S in patients who don't have a diagnosis of prostate cancer? So I let the NCC and early detection panel for many years. I just stepped down from that. I think I know that. So I recommend a baseline P. S. A. Test between if if you have a family history like that, I would get it by the median P. S. A. For men in earlier forties is 0.7 not not. So you can tell you can predict the future risk of the disease in the future. Risk of lethal disease by a baseline P. S. A. In in the early forties for all men. I I recommended age 45. Um And uh for a patient like that I would be worried they're carrying a mutation and I'm not sure I wouldn't screen them. Even at the time of their P. S. A. One of the things that we do worry a little bit about surveillance and men carrying BRC two mutations. So that's that's because those men tend to have higher risk disease. And I have a I have a 28 year old patient come to see me who has a family history like you described and and he's carrying a mutation. His p. S. A. is low he's he negative biopsy he wants his prostate out. I'm not sure we're ready to do that yet. But we we are seeing this this risk and we're doing certain we're doing research to determine what that risk is. So we can better advise these patients but based on PS PSA testing at age 40 for people with a strong family history, 45 for all others. And would you recommend that somebody like this? Go to our genetic risk clinic or see the genetic counselors. We use the genetic counselors all the time. This has been and you go to our website and see. So I I think that patients should get genetic profiling period but at the same time as P. S. A. So we it's a great service and we're seeing we're using it all the time. We do it. Men with a strong family history especially men with a family history of early onset lethal disease. Family history of early onset as you will know, ovarian pancreatic cancer. And we do as men with metastatic disease and men with adverse features locally like introductory carcinoma. So we do a lot of germline testing now it's important to tell your family members and these patients may be candidates for part inhibition if they fail standard therapy. So they're what um just to clarify that a little bit there are families who have a variety of different cancers that occur. And often if the cancers occur at young ages or in the case of prostate cancer, they are nastier in their behavior. Um There could be a genetic risk factor that you're born with and you can have your primary care physician refer you to our high risk where they can screen you to understand what your risks are and to recommend surveillance as well. So, as dr Carroll was talking about doing tests like P. S. A. Or for patients with breast or ovarian cancer risks, there are different kinds of screening. So this is actually a really important service. We have a great high risk clinic that provides that service at UCSF. So I think with the time, unless there's any other pressing question, do you have any final comment? Peter that I apologize for the miscue at the beginning. And secondly again, my email is peter dot carol at UCSF dot edu you if I could be of any help in the future, which is great and this is really so exciting to see. It's amazing what the advances are just the ability to do surge and we're going to hear more about that now from Dr win and dr wen is an MD PhD an associate professor in residence in urologic oncology and also holds the Richard and Leilani Reynold endowed professorship in urology and actually did his fellowship at UCSF as well um and has a lot of clinical interest in clearing detection diagnosis and management of prostate as well as other urologic cancers. Uh And we're really interested to hear about your discussion on local therapy as well. Thank you so much for the introductions. Let me share my screen here. I'll bring up the talk. Uh actually, so this talk actually the titles actually came from dr carol I. The original title was focal ablation. And then have a better title here, focal ablation, less morbid alternative to surgery and radiation. Who and how do we do it? And these are my disclosure. So I'm gonna go over some of the basic principles focal therapy and particularly high fu and role of focal therapy in the modern management of prostate cancer, some current guidelines outcome and then future directions. So focal therapy I think and now is going to be an important fuel an important gap in prostate cancer. Traditionally, patients with prostate cancer, we often treat the whole gland and prostate cancer as you know, it has a spectrum of disease. And our philosophy is that we should treat treatment should be based on the extent of their disease as well as the patients also. So, before we don't have the ability to really characterize that index or the the dominant tumor. Uh So we don't feel comfortable of for offering focal therapy so much. But now with the advancement in more uh complex uh imaging M. I. P. S. M. A. And the ability to do M. I. Fusion, we can actually identify the dominant or the significant cancer. And and and the hope is to to treat that why we preserve the rest of the organ and minimize the side effect. So focused area becoming an important uh aspect of the treatment for for intermediate risk cancer. And is appealing to most men because of the low profile in the side effects Aspect. So the idea originally from this mano a mano original prostate cancer, a paper in nature, nature medicine in 2009 showing that if you look at uh multifocal tumors, prostate, the dominant tumor tend to be the tumor that caused the tasks. But here they're looking at copy number variations. And this is actually a intense topic of research here at UCSF as well. So the idea is that we identify the dominant tumor precisely and a blade that and then we would prevent metastases and hopefully minimize the side effects. So, research by dR carol for many years at UCSF have looked at this and this is an example of paper recently published showing that in patients of almost over 1000 men on active surveillance. And if these men undergo multiple biopsy throughout the uh the life with surveillance biopsy, 60% of this court and then go at least three biopsy or more you can see here the the most of the progression is in the dominant tumor, not elsewhere in the prostate. So Among the candidate for focal therapy up front, 70% of those remain a candidate for focal therapy throughout over the next five biopsy. So as you can see here, the main index legion is the area that we should focus on based on this research. And so who should, who's a candidate that we should offer this to? The ideal candidate would be localized intermediate risk cancer at least in 34 cancer. And the sometimes we would offer to select the patient with least in six cancer or unfavorable four plus three cancer. The tumor location has to be away from the urethra and the rectum and the patient has to agree to a lifelong surveillance. You know, I often tell a patient this is not a key here. We can treat the dominant tumor but the chances that you the patient can develop you cancer in the future. So we need to follow them throughout their life and the location of tumor. There's several ways we can play. One would be a focal area. Sometimes we can play half of the prostate hockey stick approach. And uh most patients that we offer this, they have to have an M. I. And an M. I. Fusion biopsy to eliminate any any uh cancer that that we can miss on a systematic biopsy. And then uh if feasible, we would utilize uh PSM a pet imaging as well and the tumor location. Uh Sometimes we pick the type of energy to use based on the tumor locations and all the patients undergo for population. We would do uh the ultrasound exam just to make sure there's no rectal stenosis classification. For instance, patients in the classification throughout this is not an ideal candidate because the sound, the calcification will interfere with the sound. So how do we do? There's several ways we can treat this tumor using different energy source. And this is based on the location of the tumors. As you can see a tumor that is in the posterior area the prostate. We would use trans rectal ultrasound two bladed an anterior tumor. Maybe more fitted with laser ablation. Cryotherapy for instance. Now there's also focal irreversible electro operation. Is another way. We actually put electrodes around the tumor and deliver electric shocks to personalize the cell membrane called self that that way the tumors near the urethra, you can actually use a poster or can urethra ablation using sound wave. And uh and uh and that can be done through the the rectum. So uh for now focus now focus a little bit on high food is uh what we do at UCSF mostly. So, high fu is basically we focus high intensity ultrasound and the tissue to an area of the prostate and heated up to 85 to 95 degrees Celsius. And this is what it looks like after um 48 hours. It's cause coagulation necrosis. And three months later become a fibrous tissue. This is the actual ablation that we did here. So the uh procedures under general anesthetic this is we put the patient on the size and then insert the probe. We scanned the prostate. And then we have the M. I. images load up and we would fuse the the images together. Ultrasound and the M. I. Fuse. And we identify the target. And then we map out where to begin the ablation and where to end ablation. Typically you want to play at least five millimeter of normal tissue around the tumor to to uh to avoid uh recurrent or decreased recurrent. And the ablation usually takes about 30 minutes to an hour. And the patient goes home with the catheter for three days. And uh pretty much no limitation. They can do whatever they want. Uh If the patient uh you don't wanna catheter they can learn how to put the catheter in by themselves. And here's the current guidelines. So the N. C. C. N. Guideline uh uh said that the high school private therapy is an option for radio recurrent prostate cancer but it has not recommend high fu for primary therapy yet for to treat prostate cancer. The au a guideline based on expert opinion saying that the clinician should inform patient who's considering ablation that there's lack of high quality data comparing outcome to surgery or radiation or active surveillance. But they believe the ablation may be considered and selected appropriately informed patients. The Eu a guideline offer high fuel cryotherapy only within the clinical trial setting and not for primary treatment. German guidelines now include focal therapy as an option only for low risk cancer. So when we discuss these these options with the patient, I often ask, you know, go over these risks or how high food can fail. So there's far away that you can get a recurrent after focal ablation in this case, high intensity focal ablation. So inadequate heat. If there's not enough heat to the tumor, some will survive and uh and you can get residual cancer and uh later if you freeze the if you use cryo and if there's not enough freezing temperature there, then you can get recurrent. The other one is inadequate. Majin inadequate margin. So often uh blade about 5 to 7 millimeter beyond the tumor. But there's microscopic extension of the tumor. We will have a recurrence in the few of treatment. And then there's fuel effects if there's the prospect has a tendency to form more called multifocal disease. So you can get new cancer in the untreated area in the future. So cancer patient on this and then inadequate staging. So patient who has cancer that has already escaped the prostate out into the limit on the bone and we don't know about it, then that patient will develop the tasks even though we picked the primary tumor. So, um so here's some outcome from UCSF DR shen has been doing focal cryo for many, many years now. Here's a paper on medium, our medium term outcome for 95 patients underwent cryotherapy. So you can see here, 38 patients have a negative biopsy. Uh and actually 75 patients had followed biopsy. Among those 38 patients have No cancer found in the treatment area or whether there's two, there's two patients that develop metastases later on. These patients probably have metastases at the time of treatment that we did not recognize. Then the patient, 17 patients have a positive biopsy on the untreated side. 13 patient had biopsy on the treated side and seven had a positive biopsy on both called in few records as well as our few recurrent. Um So you can see two years of fellow free survivors at 96.2. So follow up is still short three patient has metastases, one has salvaged prostatectomy five and then one radiation. When we look at the Functional outcome, you can see that there's a decline in the sexual function of from a shim shim of 25 is a perfect score. So 18 verses 10. After treatment, the union function remained unchanged after before and after focal cryotherapy. You this is a another study of a Phase two. Recently reporting in Lancet oncology of 100 patients on phase two. Uh multi center looking using high intensity focused ultrasound using the exact uh Exact blade from inside text. So you can see here 24 month follow up, 88% has uh no evidence of recurrent cancer that is greater than uh group two and four hold land, about 60% has no cancer elsewhere. That is significant. Now in this group, you can see there's a slight decline in their sexual function. Uh this is without medication with me. With without medication. So, there's a slide from 12.9 is very slight and stable throughout. So no patient report uh stressing continent throughout the study period. There's only one grade 11 grade three adverse event unit track infection. One patient has a stricture, but that resolve after single dilation. Now, if you look at the five years of follow up, this is a prospective study of 624 patient in europe. The five years failure free survival is at 88% metastases. Free survival was 98%. And cancer specific survival, Pacific survival was 100% of five years. Only 2% has a union incontinent requiring the use of one path. How complication was rare 0.3%. You look at 15 years. Follow up after focal ablation. This is a study of 1300 men in europe 15 center. So you can see here overall, there's 100 22 patients underwent salvage therapy after three patient has developed metastases and one patient died from prostate cancer. The seven year progressive free survivals. For intermediate risk disease. It's about 68%. And for high risk diseases, 65%. So you see here um for intermediate risk disease, I would say 30% has a recurring at seven years. Now. You look at 20 years data, this is for whole gland ablation of 604 patients. You can see patients who are intermediate or uh or low risk disease. The cancer specific survival was 98% and 95%. Only 65 65% for high risk disease. So we we don't offer to high risk patients for this reason. Um And here metastasis free survival was 85% for intermediate disease, 91% for low risk disease and 58% for high risk disease. Um now the in the future I think more research is needed to improve our recurrent rate. I think our recurrent rate at five years 20% I think is too high. I think uh now with the availability of genomics and psm a pet, we uh had a better position to select patients for this. Hopefully our data in the future will show a better recurrent rate on this historical data. And we are starting to use PSM a guided ablation now and I'll go over that and then we explain some of the role for immunotherapy uh in the adjuvant setting that the paper showing that immunotherapy uh during ablation it may prime the immune system. Uh we add immunotherapy that may help reduce the current risk as well. So I think focal therapy will continue to play an important role, especially for patients with intermediate risk cancer. And uh it could be in the future. We may offer to patients who has metastatic disease and they just want the local tumor control without side effects. So are most often patient who has metastatic disease offer radiation and some patients cannot tolerate radiation, focal therapy might be a an option to to to offer those patients just for local tumor control not to kill the cancer. Um And there's active surveillance for this focal therapy have role and active surveillance. We think it may for patients who have mutations or unfavorable pathology, we may offer these to human patients with low risk disease. Um So here is an example of how we use PSM a pet or to guide ablation or select patient. This is a patient. This is a 78 very healthy gentleman with the PS 11 ahead of em I showing to legion one is a pirate five and the other one is a Pirate four lesion here at the left mid clan. This was dr I think dr biopsy and this shows at least in 43. This area at the anterior right bay was was negative. So there's no cancer here and based on the pet, there's no cancer here. Now on the random sample. We also found cancer at the apex. So I got a pet scan. So we see cancer. The apec there's another uh adjacent cancer. This is anterior a pack actually before he was sent to me for to consider ablation. And he's actually on this on the high fu schedule. And I got this pet scan. So I saw this lesion and so I told him that we have to cancel your cases. This is the cancer's anterior is very close to the urethra. We take you for high food. You're gonna have a recurrent at the apex and radiation. Sometimes the recurrence here too if they don't go so well at the apex is very close to the you protect the ureter, you might compromise the the cancer control there. So he was taken for surgery just a few days ago and he's doing very well with dr carroll. Um So that's an example of how I used uh P. S. M. A. Two stage. The better stage of cancer is you know, if I were to take that patient for ablation, he would have recurrent. Now this is a patient with at least in 43. His P. S. A. Was 15. I got a pet scan uh and show a lymph node metastases. So if this patient was to undergo ablation, he would develop metastases even though I treat the primary tumor. He will get metastases in the future. So so this is how it helps a better staging helped. Also this is another example of patient who has just cancer at the left mid glenn that was referred to me for ablation. I gotta scan and show this is another cancer for cancer that was not detected on the biopsy or the M. I. So if I were to take this patient population, we would miss this cancer over here. So these are some of the genetic uh tool that we use also to better stratify patients. Really select out the high risk patients. Uh and we uh counsel them. The high risk patient will that often for ablation will have a higher risk of recurrent. So, in summary, you know, high flow of focal therapy is associated with minimal side effects. Uh It has promising oncological outcome, but new research is needed to reduce recurrent risk and ultimately, the success of the focal therapy depends on the patient selection, lifelong surveillance and then high quality m I target biopsies use of genomic and PSM A to select the station better. Um So I like to end with an acknowledgement that dr carol had two years ago, you know, he he asked my doctor myself to expand our focal therapy program and that's what we did. Uh And Dr Sudo was instrumental in getting a budget uh in the hospital to approve for us to buy the really expensive high food machine and now we've done 100 patients in last last year and a half. So, we're excited about that. We're gonna try to report our outcome in the next two years. Hope is uh we we would bring this technology to two more patients. That's great. And so interesting to hear about things for sharing that data and what you're doing with this area. Um and I was interested in that timeline you showed with the active surveillance and then this, you know, focal a blade of therapy. So who gets active surveillance? Who has known prostate cancer? Yeah, so Dr Karen mentioned patients with low risk disease. The last prefer approaches active surveillance. And some patients may uh if they don't have access to access surveillance, it's a very intense protocol, you know, biopsy every two years, imaging every six months. The essay every three months. So very, very require a lot of commitment from the patient. But some patients may have made it may not have the resource for it and they may opted for something like this. Uh Yeah, if there's that was featured in the pathology for instance and the tend to progress in the future, then we can offer it to them. So, uh that sounds interesting that there is a, you know, really specific follow up and uh, you know, imaging and blood tests and exam, right, that goes on if you do active surveillance. So you really need somebody who knows about it and they don't just send you away to come back in a year. Right? And then if you were if you had cancer that you wanted to treat and you could do robotic surgery, why would you do this focal therapy instead? Like what would drive you understand? It's on the risk spectrum. But people must be worrying all the time that they should be doing more or less, right? Yeah. So patient uh homeland treatment as you know, has a side effect. And some patients uh sexual function is very important to them, especially for younger men. And they may not want to give that up yet. So that's one aspect, you know uh in content is not an issue so much, but the sexual function, the main thing that affect men when they decide which approach uh to a lot of men who worry about the sexual functions. So it's really that you can do this procedure and it actually helps to be more nerve sparing. Yeah. Well this procedure basically the sexual side effect that based on the patient that we did, the main pretty much maintain the sexual function. The biggest complaint I get is uh decrease in the ejaculate volume, basically. But they still have ejaculation and stuff. They still maintain the uh erections. Uh So, so that's very something they yeah, that's very important to them and they want to get something in the middle of a cancer progress in the future, then they can get surgery or radiation. It doesn't really burn some bridges. But you know, they focus on the main thing I tell them is the high risk of recurrence that they will need to monitor the cancer very closely. They may need another type of treatment in the future. But some patients they don't like that. They said, you know, I want this thing out, I want to cure now then they should get radiation or surgery, right? Yeah. It's great to have options though and things that you know, and if you do this and you know, there's a high risk of recurrence is their medical therapy that you give to patients ever to try and reduce that risk of local recurrence. Yeah. So that's that's I hope. Yes. So that would be the future. There's a trial that adding maybe an anti androgen at the time of ablation may reduce. There's a try in London. That's a question. Trying to resolve that question. I hope it's amino therapy may improve recurrent rate. So that is something in the future that we want to do is to add an adamant more cost immunotherapy and risk. But and you know, the technology has been in europe for a long time. It's only come to the US recently. Do you have a theory about why usually we get approval for drugs and they get approved in europe in a year or two. Although that timeline is shortening in many countries. But this is kind of the reverse. Yeah, the the FADA the approval for the to use high fu or for for tissue ablation a process was was was approved just in a few years ago in 2018. So most of the patients they get it but they have to pay out of pocket and it cost a lot of money. So we we didn't offer it before because monologue patients can pay for it. And uh now with the approval Medicare or Medicare will pay for it. So now we're getting more of this patient to do it. That's I think in the future you'll see more and more utilization of this technology. But the adoption of technology that are also concerned you know there's concern for abuse because obviously this is very easy to do. Community urologist can do this on anything. But if you don't do it correctly patient will suffer. So I think again the key is a patient selection and and offer to only appropriate patient. Not everyone. So do you how do you do this election? Do you do a P. S. M. A. Pet on everybody and you're doing genomics? What kind of screen do you do? Yeah. So genomic I do our patients get the genomic test. If the genomic has high risk feature I often get a PSM a pet or if I do an ultrasound and I see something different from the M. I. Or something in the uh genomic or your pathology shows something different then I will get a P. S. M. A. Or if they have a high P. S. A. And I suspect that there may be cancer outside of multiple cancer, then I'll get a PS. So they get a PSM a pet, you have to like we have for breast cancer too, you have to have some risk features that make you at higher risk for metastases or metastases to the node. Right, correct. Yeah. Yeah, exactly. So we looked at the genomic and the pathology and the P. S. A. To select which patient to get the pet scan. And now with the approval of the pet scan, that's fairly easy to get you get locally for most of these patients, you can order pet ct and they can get it sometimes insurance, give us trouble but most of the time we can get it. Not a big problem. But the PSM a pet is also available pretty widely. Yes. Yeah. Recently, only recently UCSF dr carol lead the trial on on that with approval recently. That's great. And so there's actually quite a lot of people who now have expertise at UCSF right on a variety of these unique services and um and special training also. Right. Um and that's part of bringing the new technology here which is really interesting. Um and you have quite, you do quite a number of these. Right. Yeah, we actually did the last week we did that 100 Ks in the last year and a half. So that was exciting and has been doing cry for many, many years. He has the most experiencing focal treatment. And we kind of learned together and I learned it together to use the high food technology together a few years ago and then we got the machine here. And yeah, a lot of our patient is referral actually from dr carroll c a lot of the prostate cancer and and he he will refer the candidate that he thinks appropriate for this. It's really remarkable how much this whole field has progressed and how much you can now do in terms of really personalizing the therapy and trying to reduce toxicity and so it's exciting to hear and we really appreciate your time and sharing this with us actually this evening, both you and Peter and all the work you're doing at UCSF to provide expert care for our patients. So thank you very much. Thank you. Um so we're gonna move on and talk about breast cancer, the most common cancer in women worldwide and like prostate cancer are surgeons along with surgeons across the world really and nationally have been working on trying to reduce the toxicity of the therapy that we provide our patients. And I think that's really important because if most women with breast cancer are going to survive their disease, leaving them with a lot of work reminders that impact their quality of life every single day and every minute of the day is really important. So we're really fortunate to have Michael Alvarado here, one of our breast cancer surgeons, a professor of surgery who is multitalented because he does breast surgery, but also surgery melanoma and a very highly lethal skin cancer that I'm sure people are aware of. So, um and he's actually been very interested in the area of a whole different areas of breast cancer and trying to reduce unnecessary testing and also the extent of surgery, but appropriately because we certainly don't want to leave people with higher risks. Um, so we're excited to be able to have Michael here today. And just one of the things that Michael worked on actually was a way of providing radiation inter operatively for patients who have low stage hormone receptor positive breast cancers, which is a huge I think advanced in what we do for these small cancers. Um and but tonight we're going to talk more about uh the use of more limited axillary surgery and this is a work in progress certainly. Um and there's a lot of discussion about it, which I'm often caught in the middle saying we'll put our surgeons don't do that internationally where people are still doing way too much surgery. But before we go into Michael, I want to just mention one thing to everybody who's on uh, first of all, of course, Q and A s in the Q and A box anytime. Um and then just to say, our next cancer center live Graham rounds is a collaboration with john muir. So we have a john muir UCSF educational program, it's on november 16th from the same timeframe 5 30 to 7 p.m. This is a really exciting program for us. It's called Best of the Year and our speakers will select the practice changing studies in solid tumor and human biologic oncology in 2022. And we have a speaker from UCSF and jOHn muir and the topics will include gi oncology, lung cancer, breast cancer and human logic malignancies. So it'll be really exciting remember. And november 16th and of course we'll send out reminders. So without further ado trying to platform over to you, Michael, thank you so much. Thanks for having me, I really really appreciate it. Great. So as dr rubio was saying really wanted to talk tonight about doing less surgery in the axillary or the armpit with regards to lymph node surgery um for patients and it's um and as dr Rudy was mentioning um the downside to large surgery in the axle IQ is a high risk of a lifetime of lymphedema which is extremely debilitating and so trying to avoid that is obviously an important aspect um historically kind of before clinical trials like this one called the Z 11 trial. Historically speaking axillary lymph node dissection. So removing all the lymph nodes from the armpit at the time of surgery was recommended when patients were having positive lymph nodes um both mastectomy patients and lumpectomy patients regardless of whether they were getting radiation or not. And there was really no data ever showing that actually lymph node dissection increased survival. But it was a holdover from an old Halstead or Halstead ian thought process of kind of doing more more was better remove as much as possible and the thought was that it was more of a therapy. So the surgery was was a therapy. Um but it was really kind of seen as a way to help both the radiation oncologists and the medical oncologist um determine other adjuvant therapies like systemic chemotherapy or not, or types of systemic chemotherapies and also to help planning radiation therapy. So again, not a lot of data showing that it benefited women in terms of survival. In fact, no data. Um but it was just something that we thought was important that we needed to do, but like I said, it really put women at a high risk of swelling in the arm with lymphedema. Um and also just a lot of other factors of, you know, hand strength, nerve pulling. Um just a lot of issues with that surgery that could happen upwards of 25% of the time. And then if women were getting radiation it could go up to 35% or even 40%. So there was a big clinical trial that kind of really changed practice. It's been over 10 years now called the Z 11 trial, which was only for women that were having lumpectomy. So they were going to get radiation regardless? And the thought was maybe we'll randomize women to only doing the sentinel node procedure removing one or two or three lymph nodes to find out if they were positive. And if they were positive randomizing them to completion dissection. So removing all the lymph nodes or only doing the few lymph nodes and just seeing how things went with the standard radiation. And it was for women that were clinically node negative when they went to surgery. Um they were having lumpectomy. They were going to have radiation and if they had one or two positive lymph nodes without, you know, significant large amount of disease, they went on to either dissection the big surgery or no, no surgery plus radiation. And that trial was you know, practice changing immediately. And there were still questions about is it was that okay for estrogen negative tumors? What about if there was extra nodal extension? So if the cancer had gotten out of the note And what about high grade breast cancers? But pretty much it was accepted that from now on. If women were getting them back to me and they were going to get radiation and they had only one or two positive notes, then they would not need removal of all the lymph nodes because radiation was going to be appropriate. And also the systemic therapies that the oncologist was giving was going to clear all that. And so that was done. End of story. Perfect. The question then became well what about patients that don't really meet the criteria for that clinical trial? And so what about patients that show up that have had an ultrasound of their armpit? The ax illa and they see an abnormal small lymph node and it's biopsied and it's positive. So what about that patient? Because those patients were not in the clinical trial And if they're not going to have systemic therapy or neo adjuvant therapy before surgery, if they're going to go straight to surgery, does that mean they have to have all the lymph nodes removed now because they don't fit that criteria? What about women that were having mastectomy because in theory if a woman has a mastectomy and she only has one or two positive lymph nodes, she doesn't necessarily need radiation after that surgery. And so if she's not getting radiation, do we need to do an axillary lymph node dissection to remove more lymph nodes? One to find out does she need the radiation? If she has multiple positive lymph nodes? Like four or five, would it change what's done with the with the oncologist? So um mastectomy patients there was kind of an issue with those patients that unfortunately they would typically need to have an axillary lymph node dissection because they weren't getting the radiation. And then finally the last group are the neo adjuvant patients. So those patients that are lymph node positive that are going on systemic therapy first, chemotherapies, targeted therapies. And then after the chemotherapy they get their surgery. And what if they still have a positive lymph node after that? Or what if they looked like they had a complete response? But now the final pathology shows that the lymph node is positive. Do they require a complete lymph node dissection if they were going to get radiation anyway. So these are kind of the areas that unfortunately across the country, most of the time, probably 75% of the time, or 80% of the time or even 90% of time these women are getting all the lymph nodes removed. And again, even though there's no data to suggest that that would be beneficial in any way with regards to long-term survival or preventing metastatic disease. So what about those patients that unfortunately had a positive lymph node before? Um they're going to surgery um since they were ineligible and they weren't represented in other trials, Such as a european trial called Amoros. So would they actually need to have a complete lymph node dissection? Well, what they have been doing now is kind of looking at data and a retrospective fashion saying, okay, if those patients did have all the lymph nodes removed, how many lymph nodes were positive is there a way to predict which ones would have been similar to those that were in that original Z 11 trial. And so here you can see a study that was done out of an arrundell and Maryland cancer center. Looking at almost 100 and 30 patients that were lymph node negative. But they had a fine needle aspiration that after they found it on ultrasound that was positive and they all had completion lymph node dissection. So removing all the lymph nodes and they were looking at ways to determine who only had a small amount of nodal disease and who had more. And what they found is that yes, about half of the patients only had 123 positive nodes. Which is which is really good because those patients potentially could avoid dissection. But there were some that actually had more than four positive nodes. And what they found is that if you looked at patients that had tumors less than two centimeters and there was only one lymph node that was abnormal on ultrasound and it was not lobular cancer, That about three quarters of those patients only had one or two positive lymph nodes and probably would fit this kind of concept of doing less in the armpit the axle a based on that Z-11 trial. Their conclusions were if they have tumors less than two centimeters and it's only one abnormal lymph node and it's f in a you know, fine needle aspiration biopsy positive. They should be offered what's called a targeted sentinel lymph node where you place another type of clip in the lymph nodes so that you can actually target that and find that positive node. And also do the standard sentinel node procedure to remove another two or three lymph nodes, Get that final information and then decide in a multidisciplinary fashion if they fit this kind of Z- 11 criteria. There was also data from the Memorial Sloan Kettering cancer center doing the same type of retrospective review patients that had a needle biopsy and it showed that the lymph node was positive. They had their complete lymph node surgery and again the same type of thing. There was about half of the women that only had 1 to 2 positive notes. And it was identified that the women that had three or more positive nodes tended to have larger tumors greater than two centimeters. They had fewer tumors with ductal histology. So they were more likely to be lobular breast cancers. They were more likely to have lymphoma, vascular invasion or L. V. I. And they had typically more than one abnormal node seen on axillary ultrasound imaging. So again, maybe a way to identify patients before surgery Instead of saying no you have to get all the lymph nodes removed. Maybe if they fit these criteria we do this targeted dissection where we localize that one lymph node with what we use here called a mag seed and then you can identify that in the lymph node in the in the surgery. And do the standard sentinel lymph node procedure as well. So what we're referring to as a targeted sentinel node procedure or targeted actually node procedure. And again they had the same type of conclusions. Um Not only do they think they don't need the axillary lymph node dissection but really kind of questioning even the utility of doing the ultrasound in the armpit for some of these early stage breast cancers that might be ductile histology, grade one or grade two, less than two centimeters. No lymph o vascular invasion. Is it really beneficial to be looking in the armpit to identify small volume in one lymph node if it's going to be removed at the sentinel procedure and it's not going to change what would be done before surgery. So pretty interesting data there as well. So what is the targeted actually lymph node dissection? Well there are different ways that you can localize that that clipped node um you can use intra operative ultrasound, you can do something called carbon suspension which is actually basically like tattooing that lymph node before surgery with carbon suspension. So it makes it look black. You can do a wire localization. There are radioactive seeds, you can place in it and to detect it with a probe magnetic seeds. There are all sorts of ways now and I think that's what's really important is that we never really had this technology before but now it's very easy to target specifically that lymph node that was positive by the fine needle aspiration, remove that specifically at the time of the surgery as well as the normal sentinel lymph node procedure. The mapping procedure with the dye that removes another two or three lymph nodes. And I'll just kind of give you an example of the case. Um Here's an interesting case. It's a 50 year old woman. Um that's postmenopausal. She's got a grade to breast cancer one centimeter on imaging. She had a positive lymph node that was done um after seeing it on ultrasound. And sometimes what we do and myself and dr rubio I'll talk to dr you go about it and will actually actually send a genomic assay before going to surgery. If there's a question about potentially getting neo adjuvant therapy and you can see in this case her genomic assay so that she has more of a lower risk breast cancer and probably not going to benefit from chemotherapy. Um and not gonna benefit from it in the neo adjuvant setting. So she would go straight to surgery and again she's not a typical Z 11 candidate. So what we would do is we would place that what we're referring to as a GPS clip a clip in the lymph nodes so that we can find that specifically and then proceed with a standard sentinel lymph node procedure and lumpectomy her final pathology. She's got just a little over one centimeter tumor er pr positive three lymph nodes removed. The one that had the clip. the seed has a six millimeter metastasis. The other two nodes are negative. She doesn't need the complete lymph node dissection. She gets radiation with what they refer to as a high tangent to cover the ex illa. And then the oncology team would give her the anti estrogen therapy. So we've prevented her from needing that axillary lymph node dissection which was almost always mandated and unfortunately still happens. But people are starting to realize that that's not truly necessary. What about mastectomy patients um sentinel node biopsy without the complete axillary lymph node dissection? It's likely sufficient for patients undergoing mastectomy um when they meet these type of criteria from the these european trials called Amoros um in the lotus or trials. However in those trials patients were getting radiation after their mastectomy. And the problem with that is that obviously nobody wants radiation to start but it can also be extremely detrimental to the reconstruction and cause a lot of problems with the reconstruction. And sometimes women can actually lose their reconstruction with their implants. So we don't want to force them to say well I'm not going to do the axillary lymph node surgery. So just give them radiation because that's not great. The other issue is that, well maybe I'll perform the dissection to avoid the radiation you know to prove that they don't need the radiation. So they're not gonna maybe get the radiation but they've had the dissection and then the worst case scenario is that you do the big axillary surgery, you find another two lymph nodes. Then they're going to get the radiation on top of the axillary lymph node dissection. And now the risk of the lymphedema has gone up really really high. So there are some again retrospective analysis kind of looking at patients um in this kind of situation, this also comes from memorial Sloan Kettering in new york, looking at 535 patients that were sentinel lymph node positive but did not get an axillary lymph node dissection. And as you can see here about 200 had mastectomy in about 320 had lumpectomy. And so the question was, how did the mastectomy patients do without the big surgery and without the radiation? And this is kind of a busy slide but to suffice it to say that the mastectomy patients did not do worse in terms of risk of local recurrence, distant recurrence, regional recurrence, overall survival disease, disease free survival. So it looks like they're probably our patients as well that have mastectomy that have one or two positive lymph nodes that don't need an axillary lymph node dissection and don't need radiation as well. Now again, you know these are patients that as dr rubio said that we would talk about in our multidisciplinary conference and and kind of have a really good discussion about it with our radiation oncologists and our medical oncologist. But again it does seem that there are patients that we can deescalate um in these uh situations now there is a little bit of controversy coming up here. Um I will say um now moving into the last group really quick um this is a really important aspect because in the neo adjuvant setting, what do we do for patients that are sentinel noted positive after Neo adjuvant? Do they need an actually no dissection? And one of the reasons that this is really important is that neo adjuvant therapy is becoming much more common, especially in estrogen or the so called triple negative breast cancers and also the her two positive breast cancers and even some estrogen positive breast cancers that are hurt too negative. So so more likely to get neo adjuvant therapy and as dr rubio can can can tell us unfortunately as as great as oncology is doing the chance of a complete response has gone up dramatically but there's still a lot of patients that will have residual disease. Um And so what do we do in this case now? It's true. There's no randomized data, there are ongoing trials right now but there's also no data to suggest that the completion dissection is beneficial. So it is a little bit of a quandary here. So also if patients are getting lumpectomy or mastectomy regardless residual disease in the lymph node is a recommendation. It does lead to a recommendation for radiation. So they're going to get radiation pretty much regardless. And typically it would be to the lymph nodes um as well. But Do we have to perform the dissection? Um you know, even though there we don't have any data to show that that it makes any difference now. Um these are very similar patients to Z-11, the lumpectomy trial and Amoros the European trial that had mastectomy patients, women that had the positive sentinel node did not have dissections and they got radiation and they did very well. The question is is there any reason to think that this wouldn't work in the neo adjuvant setting? Now some people have argued that well there might be a risk of non sentinel positive nodes. So there are other lymph nodes that are left behind. And yeah, that's probably true. Like in those other trials, there are other lymph nodes that have disease in them. But the radiation and the treatment that the oncologist is giving is probably going to take care of that. And you can see it is true that in about probably 25% you can have three or more positive lymph nodes when you do the axillary lymph node dissection. But the question is, you know what about those patients that have only one other lymph node or maybe two other lymph nodes. We're going to do the complete dissection and the radiation because of one or two other lymph nodes that are left behind that are most likely going to be taken care of because they're microscopic with radiation and other therapies that women are going to get systemically. And really it's too bad. There isn't any other treatment that can be used to prevent local regional recurrence. Oh but wait there is. It's called radiation. And there are literally hundreds and hundreds and hundreds of papers showing how great radiation is for microscopic disease. And so I think that's something that we have to keep in mind. Also people will say this is a very common quote. Oh but these lymph nodes were chemo resistant. But this statement doesn't really make any sense to me because for example if you look at estrogen positive tumors, one doctor rubio can tell you that a lot of those patients are not going to have a complete response anyway. So that's not gonna surprise us. And they haven't received all the treatment because they're going to get further endocrine therapy. Her two positive tubers are also not only going to get radiation but they're going to get a year of targeted therapy. Now the triple negative breast cancers I guess that might be an area where you might say well they're not getting any other systemic therapy just is the radiation good enough. But a kind of a logical thought, press for trip process for triple negative breast cancers. Is that Well if I have a 50 year old woman with a triple negative breast cancer, she's going to get neo Adjuvant chemotherapy. She's got four millimeters that's residual in the breast. She's got two sentinel nodes, one of them has a four millimeter metastasis and she needs a complete axillary lymph node dissection. That would be the standard of care because the thought is this is chemo resistant. But if I had the same 50 year old patient and we hadn't looked in her Taxila and she goes straight to surgery, she has a 1.8 centimeter triple negative breast cancer. She has to sentinel nodes. One of them has a seven millimeter metastasis People would across the country would say Oh she fits the Z-11 criteria. She doesn't need a dissection. But the question is we don't know if that patients would have had a complete response. So we're presuming that it's okay if she has other lymph nodes that those will be taken care of by the oncologist and the radiation oncologist. So it just doesn't make any sense. If that were the case then it would be there should be no Z 11 and that only patients that are no negative after neo adjuvant chemotherapy should even be eligible for a sentence. So again that doesn't make any sense. But what I'm trying to say is that there's no logical thought process for why patients need actually lymph node dissections most of the time. But as dr rubio said of course there are gonna be times with a lot of disease and multiple lymph nodes and that you know we're really worried about it. And and again that is why we have a multidisciplinary conference to kind of discuss those situations. So really has the time come. Can we select those sentinel node positive patients that might do well with without a complete lymph node dissection. Follow neo neo adjuvant therapy. I think there is um and patients should be informed that there's a very high chance the dissection may not benefit them in certain cases of course but will cause a lot of harm. And so I think it really is a multidisciplinary thought process and we should do that and not rush off to actually lymph node dissection at the time of surgery. And there is data to show um that women that with a complete actually lymph node dissection with or without do just as well. Um and there are these papers that are retrospective in nature but showing that women do well and we've looked at our own data to show very similar outcomes. So in conclusion patients undergoing upfront surgery with an image guided positive lymph node that don't get neo adjuvant therapy. Consider targeted actually lymph node dissection, mastectomy patients that we have up front surgery and have a positive sentinel node consider not doing a frozen section and discussing the case at the multidisciplinary tumor board and then finally patients that um that have a sentinel node positive post chemo really before the surgery discuss the risk and benefits engage the radiation oncologist to talk about radiation and maybe wait on actually node dissection until after the multidisciplinary tumor board meeting. So with that I thank you so much. I I really appreciate it. Um And yeah, thank you so much. That's great. Really interesting. And we've made a lot of advances which is exciting. And I love that picture as you can tell. Michael is an Abbot cyclist. And uh the pictures are so beautiful around the coast here. So I think it's really interesting about all of this. And of course it's still complicated while we're talking, I'm gonna share my screen. I hope to show you a little bit of information about uh the next cancer referral services. But I just wanted to ask you question about uh you know patients, what we know, we don't want to take a lot of notes out. But you know, a lot of women want to have a mastectomy because they don't want to be thinking about additional imaging. They don't want to be worrying about extra biopsies. They've already had a cancer. They feel quite anxious about this. You know, as we know people have mastectomies who don't necessarily need them based on the size of their tumor for many different reasons. Um So in that situation if you take a sentinel node and unexpectedly one of one note is positive. What do you do in that situation in terms of managing because you don't want to radiate for one note positive, on the other hand, you don't know if there could be more. Yeah, no, it's uh it's your you're right. It's it's probably one of the most difficult 11 of many. But you know, it's a difficult situation. You're absolutely right. I think um we I we just had a case like that um that I share with Dr Master and Doctor prions and radiation Oncology. Doctor Master in oncology. Um and yeah, we now again, there there are different positive lymph nodes. Is obviously as you know, so how much is in the is it a micro metastasis? Is it just barely over a micro metastasis is a large one. What's the primary tumor biology? And you're absolutely right. I think um what we do is we have a discussion when in the multidisciplinary group and if the oncologist says, you know, even if she had one more positive note or even to more positive notes, it wouldn't change what I'm going to do. This is, you know, this is what I'm offering her. And if the radiation oncologist says, yeah, even if she had two more positive nodes, we wouldn't do the radiation in those cases, you know, we talked to the patient and talk to them about kind of, you know, the risks and benefits of it and try to see how they feel about it. Um But you're right, it's it's a it's a tough situation of course. Absolutely. If the medical oncologist says, look I you know, I need more information to make the decision about chemotherapy or no chemotherapy or the type of chemotherapy. Um the good news is is that as you know, as I you know from our all of our discussions that you know, the genomic assays and predicting biology, lymph nodes are becoming less important than they used to, you know, 10, 15 years ago. But but it is it can be difficult but we have that discussion and there will be some patients that don't need any axillary surgery and there'll be other patients that we do go back um and and and have to take more lymph nodes. And I think what it really shows is that, you know, although it happens, you know, the best situation is to really when you do your sentinel node procedure to really take care to make sure that, you know, was it really just one lymph node, did you make sure that there wasn't a second sentinel node in there or third sentinel node because I think, you know, across the country, you know, because we know that we don't want to do more surgery. People feel that even doing less sentinel nodes is somehow better for some reason and you know, sometimes you know, I don't really maybe do exactly what they're supposed to as well. So but you're right, it can be really tough. It's a work in progress. But I think we're making great progress because we're reducing lymphedema. You know whole groups of patients I'm treating from metastatic disease. We are suffering with lymphedema and we're also reducing the nerve pain and improving the rapidity of recovery. Um And you know it's been a fascinating process and there's still a long way to go. So we really appreciate all of the information you've given us. And I wanted to close just with showing you our information about the cancer services referral center which is a single point of access. You can see the number is there and there's also one point of contact for referral for all cancer specialties which really helps you. And it's open from 8 to 6 P. Eight A. M. To six p.m. Which is great. You can even just call to ask questions which is wonderful. Um And there's a patient referral form as you can see on the right hand side which can be faxed or sense. So there's a lot of different options here. But the confirmation number to the clinic, as I mentioned, we have additional cancer center live series conferences over the course of this year which will be by zoom. So it makes it very convenient in your living room and or office. So as I mentioned earlier Wednesday november 16th we have our collaboration with john muir and this is practice changing studies and solid tumor and human biological oncology. Best of the year then we have to next year before we start into the next fiscal year, Wednesday february 15th with car T cells for human logic malignancies and beyond. Where a group has really done a lot of work and a very exciting area. And then Wednesday april 12th, an area near and dear to our heart which are novel therapies and ice by 2.2. It's the new model of our neo adjuvant adaptive lee randomized phase two trial for breast cancer. Where we've incorporated some of the really exciting gene signatures to understand, to try and personalize therapy for patients and understand what is the right treatment for the individual patients and their cancer. A new model for precision medicine and breast cancer. So we look really forward to seeing you and hearing your questions at those meetings coming up in the future. I appreciate you participating today and listening and thank you very much to our speakers. Uh Doctor Wen Dr Carroll and dr Alvarado for your excellent presentations and dr Christine. Oh for her. Uh really thinking about this series and for her support. Good night. Thank you. Thank you