Chapters Transcript Video Role of Pelvic Lymph Node Dissection for Prostate Cancer in the Era of PSMA Imaging Karim Touijer, MD, MPH Good morning everyone. It's a pleasure to welcome Doctor Tuja from Memorial Slo Catering Cancer Center. I had the privilege of working with Doctor Tuja during my fellowship and his surgical skills and thoughtful approach definitely left a lasting impression. He's led several landmark, uh, studies, including the randomized trial published in European Urology on limited versus extended the pelvic lymph node dissection. And more recently, a follow-up analysis showing extended, uh, lymph node dissection. Uh, significantly reduces distant metastasis despite no difference in PCR. Today he will be discussing how PSMA imaging is reshaping our understanding of lymph node, uh, management and prostate cancer. Without further ado, please join me in welcoming the Cure. Thank you very much for having me. Uh, it's a pleasure and a privilege to join, um, to join your program and participate in your grand round. Indeed, as Ali said, this uh topic of pelvic lymph node metastasis in prostate cancer has been a career journey in my, in my research, and I, I remember that when I first finished my fellowship at Memorial and joined the faculty at the time, Peter Scardino asked me if There is anything in I should focus my research on and I needed to have a niche so. I went for a run in Central Park. And came up after the run with the idea that I'm gonna work on pelvic lymph node metastasis because no one is working in that area, at least within my group, and that would be my, my domain for my research that would be uncontested. What I did not know is 20 years or 25 years later, is that there was a reason why nobody was interested in it because it's such a hard question to answer and such a controversial topic, but I'm glad I did and it's been um an interesting journey that I will share with you. So, uh, these are my, um, disclosures. And I will speak about part of the talk about some of the future directions. As many of you know. The concept of pelvic lymph node dissection as a staging procedure sets it up as the standard. Staging for prostate cancer beyond PSMA beyond the imaging, and the relationship is almost linear as you could see. The more lymph nodes we remove, the more likely we are going to detect a positive lymph node. So the extent of the dissection. It is intimately tied to discovering positive lymph nodes. And so it is a bit of a misunderstanding to think that by doing a limited or a small lymph node dissection, we find no metastasis and we use that argument to do less pelvic lymph node dissection. That's a bit of a self-fulfilling prophecy. We know the natural history of positive. Lymph nodes are treated with radical prostatectomy alone and extended pelvic lymph node dissection. In this paper, we have demonstrated that within the PN1 group. There is so much heterogeneity in prognosis. The majority of patients, as you can see, will develop biochemical recurrence rapidly within the 1st 2 to 3 years. However, at 10 years we could see that about 30% of the patients remain free from biochemical recurrence with a radical prostatectomy and pelvic lymph node dissection alone. It is interesting to know whether this group of patients. have a cancer that is biologically inert in the lymph nodes and therefore, Whether we did the node dissection or not is irrelevant or Perhaps this group of patients with a micro metastatic and a low burden disease in the lymph nodes, the radical prostatectomy was able to eradicate the disease and therefore has contributed to an improving in prognosis. So this question is the topic of the talk today and this question. Shows and reflects how divided we are on this topic within the neurologic oncology community. This is a survey that I did by the elite surgeons, members of the SUO in 2011, 2012, and as you can see that most participants in the survey are well seasoned surgeons performing anywhere between 50 to 3 more than 300 radical prostatectomy a year. But We were all divided on what type of pelvic lymph node dissection we do. Some remove only the operator fossa, some only the external iliac. A large group remove the external iliac, the operator fossa, and the hypogastric packet, which we call today extended or standard pelvic lymph node dissection and others do various combination of these anatomical templates. When I saw this, I embarked on uh thinking about a. A clinical trial. And in the preparation of the clinical trial, I learned a lot because to harmonize within the urology service at Memorial, what we do in our semantics and our understanding of pelvic lymph node dissection, we went through a series of Video sessions, each surgeon presenting their type of lymph node dissection, what area they call the operator fossa, what area they call the external iliac group, and where is the hypogastric. So we made sure that as we were designing the trial that we all speak the same language, we all understand the operation. I will share with you a short video of a pelvic lymph node dissection from my experience. Let me, yeah. And so we are on the right side, opening the peritoneum right here. You could see the external iliac artery. The vein in the shadow of the peritoneum behind there, you could see the ureter here and so the opening of the peritoneum goes parallel to the ureter all the way to the bifurcation of the common iliac as you could see. Here we see the medial umbilical ligament. There is a cleavage plane between the medial umbilical ligament. And the nodal packet. We developed that space. And once that developed. I open above the vast deference and lateral to the median umbilical ligament. And at this point, I will switch to the Ligasure device. And divide the vast difference. Some of my colleagues leave the vast deference intact. It doesn't really matter. I think we, at least here we debated whether dividing the vast deference causes some testicular or inguinal pain or not. I think it's probably the use of energy like the monopolar that might contribute to in some patients to a postoperative inguinal and testicular pain. Here we are at the bifurcation, so we start. The dissection and a grade. You could see the lymphatic vessels and ceiling devices, whatever the mark that is, here you see some lymphatic vessels are very good about doing the lymphostasis and uh avoiding the risk of lymphoces. Here retracting the vein laterally, finding the psoas muscle, leaving the fascia on the psoas muscle as you could see there. Identifying the operator nerve and the sciatic nerve below it and safely taking and sealing the lymphatics. And mobilizing. The lymph node packet from the fossa of Marseille. In some patients, That have aOS that is very developed or have a tortuous iliac artery that comes more medial and impedes the access to the lymph node packet. In that case, you can go either behind the vest the vessels, or by behind I mean lateral to the vessels, or you could split the space between the external iliac vein and artery and gives you an access to the fossa of Marcia. Here on Cooper's ligament, locase node, it is not necessary to take cloa because it's hardly ever positive. I think we did a study on that that showed that cloa is in less than 1% positive in high risk disease. Cloquet drains the leg and does not drain the prostates. The cases where it's positive, it's, those are patients that have overwhelming lymph node metastasis. And here we go for the operator fossa. Mobilizing the artery fossa and noal packet from the lateral side of the prostate and the bladder. Pushing the space. And Working on the feeder vessels of the uh noal packet. As much as possible, I prefer to have the nole packet. Delivered on block as one piece, it's easy to maneuver, but sometimes it's not possible. Those are the artery, the operator artery in vein and you can see the operator artery does have some perforating perforating vessels that go directly into the nodal packet. Those are best controlled prior to cutting them because they tend to bleed right on the edge of the, of the artery. And here working the hypogastric or internal iliac nodal packet as you could see. I hope you could see my video well. The neural metastasis follow or the the lymphatic drainage of the prostate follows the vascular anatomy and certainly follows the vein, the arteries, and so certainly the culprit nodes are alongside. The arterial vessels behind the superior vesicular artery, often in high risk disease are subject to metastasis. So this is the extended node dissection and as you can see, it's the external iliac, hypogastric, and operator or fossa nodal groups. And so because of that controversy, we embarked in 2011 on designing one of the largest surgical trials, uh, randomized clinical trials in surgical oncology, which at a time, a trial that was uh comparing a limited pelvic lymph node dissection which includes the external iliac. Only to a type of lymph node dissection as you, you've seen here. The primary endpoint of this trial. was um biochemical recurrence. At the time, we included open laparoscopic and robotic surgery, um. Over 1500 patients were consented to the trial, and initially we started as a 1 to 1 randomization. But given the volume of prostatectomies that we do, um, it ended up being logistically a bit of a confusing. And a very demanding tasks from a logistics standpoint. So then with Andrew Vickers, we thought about switching to cluster randomization where instead of randomizing patients to intervention A or intervention B, we randomized every 3 months the surgeons to do only Intervention A or intervention B and every 3 months, the surgeons get assigned a type of randomization. We had 757 patients randomized to the external iliac, uh, to the external pelvic lymph, to the extended pelvic lymph node dissection and the equal number randomized to the limited pelvic lymph node dissection. As I said, the primary end point was time to biochemical recurrence, and when we looked at the data and analyzed it, the trial was negative. We did not detect any difference in biochemical recurrence between the limited and extended pelvic lymph node dissection. At the same time, one of our fellows from Brazil, uh, went back to Sao Paulo and with the team there, uh, started a similar trial, a lot smaller, 300 patients, 150 randomized to a super extended pelvic lymph node dissection, and 150 randomized to a very limited pelvic lymph node dissection. In fact, They had a very limited pelvic lymph node dissection and they extended their node dissection to include the common iliac and the pre-sacros. In this trial, as you could see, there was a stark difference between the number of nodes removed, the median was 3 for the limited versus 17 for the superextended. Also, the detection of metastasis was. 3% versus 17% and so uh pathologically quite different um results uh given the difference in extent of pelvic lymph node dissection. The primary end point of the trial was was a biochemical recurrence and again this trial also did not show any. Biochemical recurrence, difference between the extended and the superextended and the limited. So, uh, within a year, within the same year, we had two trials, 2 randomized trials in urology showing that The extended lymph node dissection does not provide any therapeutic advantage in terms of biochemical recurrence. This data has Inspired the recent EAU guideline to Not recommend in the pelvic lymph node dissection in the surgical treatments of prostate of uh prostate cancer, citing that it is a morbid operation but does not uh confer any therapeutic benefits in terms of biochemical recurrence. And so, When I had the first trial, that was negative, I thought that perhaps The arms, the interventions were not the right question, and that we should have a more pure design which would be extended pelvic lymph node dissection to no lymph node dissection whatsoever. And so I started a new trial about 1500 patients, 1600 patients randomized to Pelvic lymph node dissection versus no lymph node dissection. We started the trial in 2020 and accrued about 750 patients to the trial. And with more follow up, I went back to the prior trial of limited versus extended and wanted to see if there is a difference in metastasis. So we reanalyzed the data and we found that with more follow up and looking at metastasis, not biochemical recurrence. Patients that had undergone an extended pelvic lymph node dissection had a lower rate of metastasis with a hazard ratio of 0.82 and a P value of 0.003. Then we looked at distant metastasis and we found even more striking difference favoring the extended pelvic lymph node dissection. When I saw these results and presented it to our group, we put this through extreme harsh scrutiny. We asked a lot of questions. And Is this due to solve a difference in salvage therapy? We didn't find any. Difference to biology of the cancer. We looked at the PSA level, the PSA dynamic at biochemical recurrence. We did not find any difference. In fact, we, the results stand and the results are, the benefit in terms of reducing metastasis is even more pronounced in patients that have pathologically Positive notes as you could see here with the hazard ratio of 0.49 and a P value of less than 0.001 on the interaction term analysis. The trial was criticized because there was a less than anticipated difference in number of nodes retrieved in the limited and extended. So we analyzed the data, the difference in metastasis independently of the number of nodes removed, and what we found is that This difference in metastasis is maintained regardless how many lymph nodes are removed, which To me raises the hypothesis that perhaps it's not how many lymph nodes were removed. It's where we find these positive lymph nodes, what areas we go dissect. And as I told you earlier, I did a paper of 100 consecutive patients. High risk disease to very high risk disease. In every node dissection, I sent cloquet from the right and the left separately. In this group of patients, 43%, 43 patients out of 100 had positive lymph nodes. Cloquet was only positive in one patient. All the other patients had cloches bilaterally negative, even when they had metastatic lymph nodes. So cloquet and the external iliac zone gives us more lymph nodes in terms of numbers. But a lower yield in terms of positivity. Er Studder published on this. Peter Scardino also published on this. Which is the mapping, where, how many nodes we get by a zone and where the positive nodes are, and as you can see, you can get up to 9 in a median number of nodes in the external iliac packet. The positivity is only 14%. In the operator fossa, there are fewer nodes. You can get 1 or 2 in median. The positivity is 50%. In the hypogastric, you can get no a median of 4 nodes, the positivity is almost half again 40%. So these areas here that are often dropped in the limited pelvic lymph node dissection will give you fewer nodes but more positive nodes. With the advent of PSMA where it's showing us the recurrences in areas within the surgical field or just on the limits of the surgical field. So that helped me modify my surgical technique. I will show you a set of surgeries in different patients where I completed the extended node dissection just as I showed you earlier in that first case. But then I went to these corporate areas that are more likely to harbor no positive notes. So here we are on the right side. I am finishing the extended node dissection just as you saw earlier. Skeletonizing the vessels. Here we go. And Finalizing the dissection. Then I go behind the superior vesicle artery. It looks just like adipose tissue, but if we go deeper, Often along the superior vascular artery, there are positive notes in high risk disease. And here you can see here is one. Larger notes that would have been left here is another. And the 3rd 1. Positive notes have this color, they usually are not pink, they're usually are rounded and a little bit firmer. So you could see that even after doing an extended node dissection. I would have left this sort of grape of notes just hiding behind the vessels, because often we do not look in these areas. My surgical technique has evolved, in fact, to do even more node dissection by going and looking for these areas that are more likely to harbor positive lymph nodes. And you could see here care is taken not to break these nerves. Now, I'll move the video a little bit to the other side. Cause this is just continuing the dissection. And this is another patient. OK. This is just the completion of the removal of these positive notes. Also, having done a number of salvage node dissections. Uh, allowed me to know where these recurrence could be. And so, we are going to go to another patients this time on the left side. Right here it's the operator of fossa. Surgery as usual. Here is a positive note. So not to be lost, so this note is gonna be cut separately and sent to pathology. Or individual evaluation, no frozen, just routine pathology. And again, finishing the extended node dissection. And often medial to the internal iliac or hypogastric artery is also an area where positive nodes are. Here you could see everything looks normal. And there is a positive note there. If you, if you look at it from. Laterally where we usually operate. You can't see anything. It just looks like adipose tissue. These are deeper nodes, so you have to look for these positive nodes to find them. And knowing where the positive nodes are. Allows us to Often go to these corporate zones, anatomical zones to modify the template. And so now it looks more obvious and the node is there. Superior vesicle artery. And finalizing the dissection here. For the sake of time, I will uh move again. And so we looked, as I said, difference in salvage, and you could see there's no difference in time to salvage therapy or type of salvage therapy these patients have received, so the difference in metastasis, it cannot be explained by subsequent therapy. Again, we looked, we first. Analyze the data, the difference in metastasis from the time of radical prostatectomy to the time of metastasis. We did another analysis looking at the difference from the time of biochemical recurrence to metastasis, and you could see again with a P value of less than 0.001, a hazard ratio of A ratio of 0.76, there is a significant difference in metastasis, suggesting that perhaps it's an event that occurs after the development of metastases. Keep in mind that about 42% of these patients had a persistent PSA, especially those with positive lymph nodes. So, this trial created a lot of controversy and recently in August in the Journal of Urology, the team from Melbourne, Australia, and Switzerland from Bern, Switzerland. Collected a large retrospective data set of men that had undergone radical prostatectomy with pelvic lymph node dissection and without pelvic lymph node dissection, and they analyzed across all the risk groups and analyzed the data set looking at difference in recurrence and difference in uh metastatic progression. And as you could see there was no difference in recurrence between groups, however, men that had undergone. Me that had undergone a pelvic lymph node dissection. And were either high risk or intermediate risk, had a significantly lower rate of metastasis. Compared to those that had only radical prostatectomy without pelvic lymph node dissection. This retrospective study supports the finding, the controversial findings of our trial showing no difference in biochemical recurrence. But a significant difference in metastasis. Here they did not purely look at biochemical recurrence, they look at recurrence-free survival. In the conclusion of their work, they basically said that in this study of 2,343 consecutive patients with prostate cancer, An extended pelvic lymph node dissection was significantly associated with a lower risk of metastatic events in patients with NCCN high risk and intermediate risk, and the take home message is that A pelvic lymph node dissection or an extended pelvic lymph node dissection, that is, is To be performed at the time of radical prostatectomy and intermediate and high-risk disease. With the advent of PSMA it's changing our understanding of metastasis in prostate cancer in general. It is also opening our eyes to the metastatic lymphatic pattern, spread, and dissemination in prostate cancer. I always share this, this, uh, this picture. This is one of our patients that was found to have a prostate cancer metastasis in the myocardium. And in fact, with hormonal therapy, this regressed. I don't think any of us would have thought that of this, of this type of spread for prostate cancer. But what we know about the performance characteristics of PSMA in the lymph node is that it has a very high specificity. However, the sensitivity is quite limited to 33 to 45%. And that is due to the limitation of size of these lymph nodes. The smaller the lymph nodes, the more likely they are to be missed by PSMA. Perhaps some cancers don't express PSMA. Perhaps some cancers express PSMA. But prostate cancer that is, are missed on PSMA. We know that less than 5 millimeter, the performance characteristics of PSMA drops drastically. This is a series part of a trial that we participated in, and there were 30 patients. Um, all high risk that had Not on metastasis. Here is a sample of 10 patients. The PSMA detected. Positive notes in 3 patients. The other 7 patients had positive notes with a negative PSMA. I'll show you some of the samples. So this small data set also confirms a sensitivity of about 33%. And what you could see some of the missed nodes are either 1 millimeter in size and I congratulate our pathologist for even finding these nodes that small, but the PSMA could also miss lymph nodes that are 2 centimeters in size, and both express in PSMA. Now, here's an example. 74 year old man with grade group 5 disease, CN0 on PSMA, seminal vesicle invasion. Tumor here in the prostate and here on the MRI as you can see. I performed a lymph node dissection on these patients on the left side, he had 2 out of 8 node positive. On the right side, he had 8 out of 14 positive lymph nodes, so a total of 10 to 22 positive lymph nodes. I would say that these patients for Those of us that believe if the PSMA is negative, you should not do a pelvic lymph node dissection. In these patients, we would have left 10 positive lymph nodes, despite a negative PSMA. Another case Two positive lymph nodes on the left side, one is 9 millimeter, one is 17, performed the extended pelvic lymph node dissection on bilaterally, and he had 4 out of 12 on the right. And 4 out of 18 on the left that are positive and 1 node here positive in the pre-vesicle space. So certainly the PSMA can alert us to positive notes. It does not give us a complete tally of all the positive notes, and sometimes it tells us that the notes are negative, but they are indeed positive in high risk disease. This is another interesting case. 53 year old man with biochemical recurrence after radiation therapy and disease progression in two left pelvic lymph nodes and one inter aorta caval nodes and one perortic nodes as you can see here. Biopsy of the prostate showed no viable cancer, so I embarked on a salvage. Retroperitoneal and pelvic lymph node dissection in this man with the idea that he only had 4 positive nodes. Here is his pathology. On the right pelvic nodes, 2 out of 11 were positive. On the left pelvic nodes, 11 out of 19 positive, not 2. On the intra-aortic cable, 31 out of 35 nodes were positive. On the para aortic node, 15 out of 15 were positive. On the pre-sacral and bilateral common iliac, 13 out of 13 were positive. On the left common iliac. 12 out of 12 positive. This man did not have 4 positive notes. He had 84 out of 105 positive notes. We only see the tip of the iceberg with the PSMA. PSMA is interesting because it is showing us lymph nodes that are located outside of the template of our extended template, so it informs the surgeons not to do less pelvic lymph node dissection, but more informed and perhaps even more extended pelvic lymph node dissection. Examples, the pre-sacral or the missorectal nodes, and these mesorectal nodes are still a very technically difficult lymph nodes to reach because we operate in an area where we don't usually operate and they are embedded in fat. They're usually small and hard to, to find. And that's why the future directions. Would be the use of. Tagged or fluorescent or radio labeled PSMA that can allow us to detect positive nodes and basically color-coded the site of metastasis the same way you could do it for, for uh positive margins. These are some of the pictures from a pilot study that we are uh current currently um doing at Memorial. Here, you could see the positive lymph nodes with the fluorescent PSMA. Here you could see even in the prostate the site of the positive uh disease. This is the view you would get. Here you see seminal vesicle invasion here, here, here and here, and tumor at the apex. So certainly this is one area of growth of our research and hopefully uh we can get there. There are several products and their study right now. At the same time, I memorial Tim Donahue that many of you know is doing similar research but tagging and coding, color coding the myelin fibers and hopefully that in the future we will be able to um Have the nerves. Coated with the color intraoperatively, the metastatic sites or the site of disease also colored in, in a, or tagged in a different color and allowed the surgeons to have a more informed, almost like a GPS type of surgical field. So in conclusion, the PSMA imaging will improve the staging capacity of the pelvic lymph node dissection. It will not replace the pelvic lymph node dissection because of its limited sensitivity. Today we have information and level 1 evidence and level 3 evidence, level 2 evidence showing that the extended pelvic lymph node dissection reduces the risk of metastasis. I thank you very much for your attention. And look forward to your questions. Hi, Karim. Fantastic. Presentation. This is uh Bruno speaking here. Um, I do have a quick question for you about, can you hear me? Yes. Oh, perfect. So, yeah, no, I have a quick question about risk assessment. Um, how are you currently risk ratifying this patient and selecting them for uh lymph node dissection or even extended? You know, this traditional systems like NCCN, uh Damico, they feel outdated to me. And you know, there are some emerging data now suggesting that only unfavorable pathology like ribiform, introductal pattern 5, I, you know, are truly predictive of uh metastasis. So I'm concerned about doing extended lymph node dissection in patients with intermediate risk prostate cancer, and this is, this is a very broad, you know, uh, you know, risk group. And, uh, even like if you look for bladder, extended lymph node is for bladder, and there's level one data suggesting that it can even increase mortality in 90 days. So how This intermediate risk patients for uh extended lymph node dissection. Yeah, Bruno, good to see you and thank you for, for your question. Uh, in fact, in, in our trial, we, we found a benefit. Across risk groups. We don't operate on low risk disease and in on a, a subset of favorable intermediate risk disease. Those patients in our center go to active surveillance. Another portion of the patients um in the intermediate risk group go for focal therapy when they meet all the Eligibility criteria. So certainly if we see an indication for radical prostatectomy, it's an indication for a pelvic lymph node dissection because our data from a randomized trial showed that all of those risk groups uh do benefit. We do have a paper with Andrew Vickers where we did the decision analysis. And showed the benefit and harm of the pelvic lymph node dissection across all risk groups. And it is a very interesting mathematical and a decision curve analysis paper that will be coming up in the Journal of Urology soon showing that Every time a a radical prostatectomy is indicated, a pelvic lymph node dissection is indicated. I don't know how to explain the SOA trial that showed that the men that had undergone a pelvic lymph node dissection had a higher mortality than those that had a limited. Uh, but, uh, bladder patient population is different than the prostate patient population in terms of morbidity. Karim, uh, Mark, uh, here, uh, welcome. I wanted to say hello and uh it's always good seeing you. Outstanding talk and obviously, uh, a career's worth of work, uh, that's very, uh, admirable. Um, you know, it actually reminds me of, I, I don't know if you remember there was a paper, you know, between Walsh and Carter that was published early 2000s, you know, remember he was the one looking at natural history of, um, extent of limited, uh, no dissection versus more extensive. It was kind of a joke at Hopkins when He compared his, you know, 2,000+ people with Belle Carter's limited section. So the joke was that you had the good surgeon and the bad surgeon, the good surgeon being the extended lift, the one that did the extended nodes, and the one that did the kind of the standard nodes, and, you know, look, obviously there were differences in lymph node yield, you know, you, when you do the extended, you get more, obviously, um, but one of the interesting things, even though again, it wasn't randomized. But it was kind of a head to head comparison, you know, he did observe that at least in, uh, you know, some of those patients with a lower nodal burden is less than 15% and nothing else, right? This is kind of seeing what the natural history of it was that these people were able to maintain long-term uh biochemical free survival, um, with that type of dissection. So hence your for into this entire field. Um, Bruno stole my thunder a little bit because that's one of the questions I was gonna ask. Uh, you know, I guess my question to you is, how, how do you, I'm, you know, curious how you reconcile that in your own practice? Do all your patients get the extended? Or do you do some type of risk stratification in yourself as you described to maybe perform less of an extent. Because we know that, obviously, one of the things with the more nodes and more extended, uh, the section that we take out that can lead to higher morbidity, right, to the patients, whether it's lymphocele, risk of operator nerve, you know, um, injury or vascular injury. So just curious how you personally do that because I don't routinely do an extended, you know, I'm guilty of that. Hey, Mark, good to see you. So we, I do an extended in all patients, I do a radical prostatectomy on. Uh, some of my colleagues, I would say that occasionally will skip in a favorable intermediate risk, we'll skip a pelvic lymph node dissection. We only do the extended because when we compared the mortality of extended versus limited, we found no difference. When you compare the, not mortality, morbidity. When we compare the morbidity of any node dissection versus no lymph node dissection, definitely it's a shorter operating time, less drainage, less lymphoria, less lymphocele, less venous thromboembolic events are all significant. I just want to note that uh in the recent EAU guideline, they made the argument that it has some morbidity, the pelvic lymph node dissection, and they cited lymphoceles in up to 17 or 20%. And in fact, when we looked at that data. In their review, collaborative review where they derived those numbers, they only quoted the highest number from a study that was never published. And so it's a bit misleading. In our hand, the lymphoceles are about 3 to 4%. Yeah, I agree. My, my love fil rates about 4%, actually it's less than that but uh early on for 4%, so exactly, it's less than 4%. Any other questions? Well, I, I do, I do. It's Bruno again, just one quick question. So when you get these patients with a positive lymph node, how do you follow them? You, do you send them for, you know, radiation, you know, ADT based on stampede, or you just watch their PSA and if they go up, the PSA if they have a biochemical recurrence, then you intervene. Yeah, so that's uh that's an important question and for brevity, I took the part of management of PN1 out of the talk. Uh, so we do closely monitor them every 3 months. And if they develop biochemical recurrence, We wait until their PSA reaches 0.2. We obtain a PSMA PET scan. And based on the results, we will treat them with either ADT and radiation therapy, or ADT radiation therapy and stereotactic radiation if they have a positive note. The majority of these patients are going to recur in, in the pelvis. Occasionally some very high-risk patients might develop metastasis in the postoperative distant metastasis. Those probably have the distant metastasis. It just was not detected before the surgery. The worst players are the patients that have a persistent PSA after radical prostatectomy, and we have published on that that their outlook is quite concerning. Thank you. You're welcome. Alright, thank you very much, doctor. That was great. Great. Thank you all for having me and I wish you a very good day. Be well. Thank you. Right, now we're gonna move on to the uh one of our subs uh presentations. Um, I'll introduce Stella Grecos. So are you there? OK, perfect. OK, let me share my screen with you. Published September 25, 2025 Created by
