of selected topics. Today we are going to focus on the topics of endometrial cancer. I am Dr. Fernando Heredia. I am an associate professor at the University of Concepción in Gynecological Oncology at the Clinic of Health Concepción in Chile. Today's webinar is being presented in Spanish, English and Portuguese. And we are going to give you the instructions here. You can also find them in the chat, as well as in this slide that appears at this time. Here we have the indications in Spanish and here we have the interpretation icon where you must select which language you want to listen to. You can also turn off this option and go to the main room. So, we have a great session today. We are going to focus on endometrial cancer. So, it is my honor for me to introduce our speakers today. Dr. Andrea Mariani from the United States, Isla, Mexico. Dr. Eduardo Paolino from Brazil. Dr. Hélica Nogueira Rodríguez from Brazil. Dr. Hanna Simos from the United Kingdom. And finally, Dr. Andy Winney from Argentina. So, please know that we are going to record this webinar and it will be available on our IGSS educational portal. You can ask your questions through the questions and answers session. We will ask the questions at the end of the talk and we will try to answer as many questions as possible. So, without further ado, to kick off today's program, we are going to look at the presentation that is called here, the evaluation of endometrial cancer. And who could be better than Dr. Mariani to talk to us about this topic? She has produced many quotes regarding this topic in the management of endometrial cancer. So, thank you, thank you everyone. I have studied the subject or the patterns that endometrial cancer has and the role of endometriosis in endometrial cancer. So, at the beginning of this century, we were a population of patients, like a third of the patients who had cancer, who were at risk of having positive pelvic nodes, or positive 0.3% ganglions with an invasion in the dermis of the tumors. And we called this criterion, which was called the Mayo Criterion, of the Mayo Clinic of Minnesota. So, using these factors and all these parameters, we were able to decide which were those patients who needed total endometriosis versus those patients who did not require, who did not have to do this procedure. But then, in 2013, our friend and colleague from Memorial Sloan Carter, Nadim Aburusto, came to the Mayo Clinic and he told us to do this with the endometrial ganglions. So, we started to introduce in the ganglions and we observed a rapid growth of the performance of these lymphodectomies. But how did we get to that point? And how was it that we were able to convince them to do this with the endometrial ganglions? So, to answer that, we had to answer this question first. If that was something therapeutic in that case. And if we look at the Cochrane Library, in 2017, a review was done that told us that by making the difference between these two procedures, there is no difference in oncological cancer and there is a greater risk of lymphedema and lymphosis. So, what about prostate cancer? And even there, we see that there is no significant therapeutic effect, clinically speaking. In particular, these randomized trials, what they showed us was that pelvic lymphodectomy does not improve the survival rate in those cancers that have a low or intermediate risk. But what about the paraortic area? In fact, we know from the data of the Mayo Clinic that 62% of patients with positive results have tumor dissemination in the paraortic area. So, is there any hidden dissemination in patients who have a tumor apparently confined in the pelvic area of the breast? And the answer is yes. There is this study done in Japan, in which they looked at 15 patients with positive pelvic cancer and negative paraortic. But when they did more studies, they found that 73% of these patients, that is, 11 out of 15, had a hidden tumor in the paraortic area. So, we can conclude that there is a tumor dissemination in the paraortic area in the vast majority of patients who have positive lymphatic damage. So, if we look at the therapeutic role, we look at these retrospective studies that have been done, and we see that there are some messages in the literature that are different. Some say yes, that it can be therapeutic, while other publications say no, that it is not. Here we have the most famous study on the effect of surveillance in these aortic lymphadenectomies, where these two procedures are compared in patients who have some type of high risk in their characteristics. And yes, we see that this aortic lymphadenectomy improved the clinical oncological results. But these are retrospective data, where we see that there is a difference when chemotherapy is used in groups. And it is very important to note that none of the patients received chemotherapy and radiotherapy in combination, because only 8% were serous. Here we have a study, a meta-analysis that was done in 2018 that focuses on retrospective studies, where it is compared in the pelvic area and the paraortic area, and we see that PA improves the rate of suffering. So, what they have included here in this meta-analysis lets us see that when we look at the therapies, only one of our documents has a combined approach. Most of us simply have chemotherapy or radiation only. But if we look at that publication with the combined approach with both chemotherapy and radiation, the retrospective data shows that patients who only had pelvic lymphadenectomy are doing better, but they received more multi-modal aid therapies. Therefore, what they were able to conclude is that this multi-modal aid therapy with radiation and chemotherapy is more important than what is done with lymphadenectomy. If there is no therapy of that kind, then the therapeutic effect will be more significant if lymphadenectomy is done. But there may be a role there in this case, but it will be less clinically significant if they receive both radiotherapy and chemotherapy. So, what happens with the data from Mayo Clinic when we talk about this topic? Well, we have here this study from 2010, which are old retrospective data where we see that PA-LNA improves the rate of survival. Patients received here only radiation or radiotherapy combined with chemotherapy. So, when we look at more recent data from our Mayo Clinic, they only focus on those patients who have positive parabolic nodules. We see that the most important predictors of survival are those of histology, and in particular these patients who have chemotherapy combined with radiation are doing much better. So, what we can conclude here with our patients who have positive parabolic nodules, we see that regardless, the result improves, and it is important to see that the biology improves the prognosis, and the result could not be predicted there. In particular, those patients who did not have endometrial cancer as a prognosis, regardless of chemotherapy, the patients died in spite of this. Here we have a similar document from Korea, patients with positive radios, and even here we can see that some patients have the radiation that was suggested, others are combined with chemotherapy, and even here, in this case, with the retrospective data, we see that the parabolic anatomy significantly reduces the recurrence in all groups. However, it makes a difference in the survival rate only in the group of radiotherapy, but not when combined therapy was given to these patients. And therefore, the administration of a combined treatment, chemotherapy and radiation, reduces the importance of the potential therapeutic effect of doing this procedure. In this document, we see that the endometrial cancer patients are doing quite badly, regardless of the degree to which this endometriomy is done. And here we have a similar study from Mayo Clinic, with patients who have endometrial cancer, which was quite bad for them, and most of the recurrences are hematopoietic. This means that the battle has been lost in the distance and not in the parabolic or pelvic area. With respect to this endometrial cancer and the therapeutic endometriomy, we see that the survival rate is less likely to improve if the patients who have these positive nodes are likely to die due to other cancers. And a combination of adjuvant therapy, chemotherapy and adjuvant therapy, we see that the results improve ecologically and the clinical significance of the endometriomy is going to be reduced. Now let's look at the sentinel lymphatic nodes. Does it work? Here we have a meta-analysis carried out in 2018 that tells us that from a diagnostic point of view, it works quite well. But do we have prospective data? Yes. This is the FIRE trial, which even here we see that it worked quite well from a diagnostic point of view. And yes, it also worked very well in the prospective trials focusing on those high-risk patients, those celiacs. So what can we conclude with this topic? Well, yes, sentinel nodes are a tool of superior diagnosis. But what about oncological results? Do they look affected? Here we have a paper made in Canada in which we see these sentinel nodes. We see that the patient has less recurrence in the endometrial sites because we can identify these nodes much more than in normal sites with metastases. So the sentinel node is superior to the endometrium to be able to identify the lymphatic metastases. We can see fewer lymphatic recurrences. Then we did the collaborative work with the Memorial, where we compared a series of pelvic and paraortic endometriosis with a newer series of Memorial seeing these nodes. And in recent years, we have published almost one document per year. That is, every year we have done it by looking and doing this analysis. And we have concluded that sentinel nodes, in the endometrial versions, have similar diagnostic results and we can find in patients who have these positive nodes and the oncological result is very similar. And this is more than anything else in these retrospective analyses and this was the conclusion we came to. So now let's answer this question. Can you complete the pelvic and paraortic endometriosis if the sentinel nodes are positive or if they have some positive congealed sections? An article has been made about this and even here a comparison was made of those patients with the positive nodes of Mayo Clinic doing this complete procedure while those who did it with sentinel nodes. And we see here that there was little difference in the number of patients who received chemotherapy versus external radiation and it was expected that patients with lymphedotomy had more removal of the congeals. And what we observed was that when it came to patients with total lymphedotomy versus only with sentinel nodes, we see that there was no significant difference in the progression or in the survival data. The oncological outcome was exactly the same. And the predictors also of the survival had to do with tumors. And if we did chemotherapy and radiography after surgery, then we see that a multivariate analysis, so these were the conclusions, that a combination of chemotherapy and radiotherapy seems to give a better outcome. But biology is the most important predictor in the case of oncological outcomes. So before concluding that if there are no bulky nodes, then it is very likely, it is not likely that lymphedotomy can give us a significant therapeutic contribution since they are receiving a combination of chemotherapy and radiotherapy. And when the risk of this parabolic progression was 3.7 times higher in the study of the sentinel nodes, the rates of isolated parabolic progressions were quite similar. So this finding emphasizes that many of the parabolic progressions are associated with distant and concomitant dissemination. So before I answered that we do not treat patients when we do lymphedotomy, if they have a positive outcome in the frozen section of the sentinel node. So what is missing? Well, we are missing large data from the prospective on the oncological outcomes in those patients that have been treated with the sentinel nodes only. And so now we have been working with this prospective trial in collaboration with the Memorial. And well, what about isolated parabolic? So we see that in general this is a fairly rare event when we look at the series that was carried out here in Camayo. And when we look at the patients who have this and it is done in a multi-stage, in those nodes, we see that 30% of the patients who had the isolated parabolic had in fact a hidden dissemination or pelvic propagation. So before this, we see that it is a rare event and even rarer if we do these multi-stage pelvic nodes. Thank you very much for your attention. Thank you, Dr. Mariani. That was an excellent presentation. And please remember to present your questions using the Q&A. Let's start with the questions and answers part with a small survey. Here it is. One of the next features are not part of my criteria. Please select. Okay, everyone is answering now. Keep voting, keep voting. Voting everyone. Okay, we are now closing the poll. What's the virtual tie there between two options? Yes, Dr. Mariani. What is not part of the Mayan criteria is the involvement of the lymphoblastic space. And the reason for this is that we look at it and recognize that it is a very important factor, but it is difficult to know that this during the frozen section. And the Mayan criteria are actually based on this section, this sectioning. So that's why this was not included within the criteria. And apart from this, the inter-observation, the diagnosis of the involvement of the lymphoblastic space is sometimes not something that agrees. Yes, just another comment about tumor diameter. This is a very important parameter and it is relatively easy to simply measure during surgery. So that's why it was an important factor in the Mayan criteria. Thank you very much. Do we have some questions? Yes, we have some questions. Do you treat with chemo? Do you treat with chemotherapy? Yes, so what we are seeing more and more is that these isolated cancer cells are a parameter that is more likely, according to the data we know right now, we are still working on the data on some of the things that are not yet clear. But what we know so far is that these isolated cells become important if there are risk factors. So, for example, if you have an aggressive tumor, if you have a serious endometrium cancer with a lymphoblastic infection, and also isolated cancer cells, this becomes more like a patient with positive ganglions. So, one assumes this case as a patient with positive ganglions. You can then do it with chemotherapy or radiation and chemotherapy. However, what is not yet clear is the meaning of isolated cancer cells in patients who do not have risk factors in the uterus. So, patients with grade 1 or 2 endometriosis, an invasion of at least 50% and without lymphoblastic infection, but with isolated cells. We do not know the meaning of that so far. Personally, I know that there are some colleagues in the literature who say that is not all that. But my answer at this time is that we still do not know. Because this may still be a microscopic disease that can grow. So, we still need to have more data about it. But for the moment, both in May and according to what I know in Memorial, we also decided to manage these patients with observation. And we do a close follow-up. So, again, the meaning of the latest depends on whether they have risk factors in the uterus. We have another question from Dr. Waldo Jimenez, who was originally from Chile and now works in Canada. And he says, patients with positive pelvic centenal ganglia, what kind of treatment is recommended as an aid? It's a fantastic question. And it focuses mainly on the same discussion about lymphadenectomy. Because the more I think about this, I've been studying lymphadenectomy for a long time. And both radiation and lymphadenectomy, from a therapeutic point of view, if there is a therapeutic role, are localized treatments. So, what we have seen, for example, in our comparison with Memorial, is that lymphadenectomy can reduce the amount of parochial recurrence. So, it's a local treatment. There is a disease there. Sometimes it is removed and the parochial recurrence can be reduced. But people die because of this disease. So, in general, the decision to do a parochial radiation extension is a decision if you want to prevent parochial recurrence. But it's not likely, according to the data we have so far, to give you a better survival. So, at this point, we don't do this routinely. But it certainly is a reasonable approach if we want to reduce the potential role that parochial recurrence can have. Do you know if there is any international prospective trial regarding this issue, particularly regarding parochial lymphadenectomy? I'm not aware of this, but maybe I don't know. Do you know of any prospective trial that focuses on parochial lymphadenectomy or parochial radiation? Please, feel free to tell us so we don't exclude you from this. If there is a trial, please let us know. But as far as I know, I don't know of any that focuses on parochial lymphadenectomy or parochial radiation. Also, because the problem is that to do a trial is very difficult. Why? Because you need to focus on the patients with positive ganglions, and this is limited. Second, most patients with positive ganglions are at high risk, most of them. I'm not saying all patients, but most of them. High risk, etc. And so it's more likely that they die due to this distant recurrence. So, it's very difficult to have the numbers for this because the patients that are most likely to benefit from local treatment are probably patients with grade 1 tumors. So, probably, if we do a trial of patients with endometriosis, the positive endometriosis grade 1 ganglions, maybe there are some good results, but it's very difficult to have the numbers to be able to do it. Yes. So, now a more philosophical question for you. Here it says, how were you able to change the paradigm of doing pelvic and parochial lymphadenectomy to just do the mapping of the sentinel ganglions? What made you make the change? Because if you could do that in a large center, maybe we could do it too. What gave you that switch? Yes. So, first of all, we started looking at the data and the data that we had gave us an indication that there could be a potential to decrease the recurrences, but it wasn't so convincing. Those data were not so convincing of the survival result, but then what convinced us was the case of our friend. Our friend Adiman Burustum came to the Mayo Clinic and we started looking at our data together and we decided to take the risk. So, we joined the data from the Mayo Clinic, the historical retrospective with the data from Memorial, that they were starting to do sentinel ganglions, and we shared the data, we looked at those data as friends, and we trusted, and at a certain point, it was evident that the data were going in a certain direction. So, what convinced me was the data, but also the case of a friend. And how important is that, the collaboration? That's the main thing for everything. Now that it's easier to communicate, for example, from Chile to the United States, live and be able to share things like we're doing today, it's wonderful. So, thank you Dr. Mariani, and we still have a lot of questions, but we have to continue with the program. Thank you very much, it's good to meet you and an honor to participate with you. So, our next speaker will be Dr. David Isla, a good friend, with the presentation of if there is still a role for laparotomy in endometrial cancer. These days, when we feel that the standard for surgical treatments are almost endoscopic for everyone, where do we locate laparotomy? So, please. It's a pleasure to greet you, dear friends, colleagues. Thank you very much for the invitation to Dr. Audrey Sonoda, to Dr. René Pareja, dear friends, colleagues and colleagues. With the topic that I am going to present, if there is a role for laparotomy in endometrial cancer. My name is David Isla Ortiz, I am an oncologist surgeon, I am the head of the Department of Oncological Gynecology of the National Cancer Institute in Mexico. Let's look at these graphs, which are very interesting and make a stratification with respect to low, high and medium income countries, where it is seen that up to 10 times the incidence has increased worldwide, with an increasingly rapid trend of growth and that is seen year after year. This is reflected in a change in lifestyle and a greater prevalence of risk factors and that are associated with this disease, obesity and physical inactivity. And that has been seen with a very important reflection in the new generations. And in this publication we also see some graphs that are of great importance, where we also observe that laparoscopy has increased over time and if we observe the different years, 2002 a 6.5% and in 2011 more than 30%. This has also been seen with logarithmic growth to date. And in the next graph we observe how the graph shows a decline between the days of hospital stay, but it is still the difference of 3 days in open surgery compared to 1 day in laparoscopic surgery. It has been decreasing and I think that now more with the use of less radical procedures like ganglion, this hospital stay will probably be much more reflected and with a much greater decrease. And mention that laparotomy, surgery, hysterectomy, salpingoforectomy is the treatment standard in endometrial cancer and there are or procedures are carried out that are part of the stagification of endometrial cancer, especially in those of intermediate and high risk, which is lateral pelvic lymphoanectomy and paraortic lymphoanectomy. And the sentinel ganglion, that biopsy that is being carried out for the identification of the first ganglion relief is of utmost importance, since it has been able to avoid performing these lymphoanectomies and reduce the risk of complications triggered or produced by this lymphoanectomy. Also, the procedures of radical hysterectomy that are carried out, especially not in the single involucrum at the level of the cervical stroma, which has already been seen that the same or with a single type A hysterectomy can be sufficiently eradicated, but not in those that are voluminous tumors and that are incipient in terms of the extension to the parametrium, a radical hysterectomy can be carried out, especially to have safe margins and to make an adequate evaluation of the parameters. And in those young patients that we have seen commonly in our hospital centers, the preservation of ovaries with certain characteristics, both of the tumor and of the stage and the characteristics of the patient, a preservation of the ovaries could be done. Returning to the question, there is still a role for laparotomy in endometrial cancer, and well, considering that the standard is laparotomy, and what is around this laparotomy are the different approaches, minimally invasive approaches such as laparoscopic, robotic surgery, but also vaginal approaches that come to be with less response to trauma, and this directly affects the patient with better results, both in the trans-operatory and in the post-operatory, and a much faster incorporation in daily activities. There is also, obviously, a combination of these minimally invasive procedures with vaginal abortions. But laparotomy, and going back to the topic, what could be the indication? Those patients who are not candidates for laparoscopy, either due to physical conditions, to maintain a very forced position during laparoscopy, either in a very forced Trendelenburg position, or due to the placement of the legs, who do not have this disability, or due to the functional state, or due to problems, both cardiological and pulmonary, and also due to the disease itself, large uterus and large tumors, or due to the use of the manipulator, which in some cases can have an effect of lethargy. Also in those stages 2, 3 and 4, which can be convenient to do cytoreduction, laparotomy can probably be the best indication. And in those cases, when there is a tumor recurrence, laparotomy becomes of utmost importance for the management of these patients. But let's look at the first point, the non-candidates for laparoscopy. Considering that minimally invasive surgery, compared to the open one, is an approach, is a way of access, many studies have been carried out, both retrospective and prospective, and in this review by Cochrane, it talks about the estimated blood loss, and laparoscopy was associated with a large reduction, and statistically significant, with respect to blood loss, compared to laparotomy. A point in favor of laparoscopy. With respect to global survival, and free recurrence survival, in the first point, there was a non-significant increase in risk of death, of laparoscopy versus open one. And with respect to free recurrence survival, it was not statistically significant, a difference in the risk of recurrence of the disease. And in this evaluation regarding quality of life, also a point in favor of laparoscopy. Patients with laparoscopy, reported much higher scores, and were significant in the functional evaluation of patients, in the postoperative of minimally invasive surgery. With respect to the guides of the NSCN or the European ones, this is presented and it is a recommendation, that surgery could be both open and minimally invasive surgery, with certain benefits with respect to the last approach, this in the publications of the systematic review of Cochrane. In this prospective study of Lab 2, whose main or fundamental objective was, to compare laparoscopy versus laparotomy, for the surgical statisfication of uterine cancer, where the results of the surgical statisfication of endometrial cancer, can be performed through laparoscopy, without intraoperative increase of any or lesions, with less postoperative complications, and a shorter hospital stay. In the follow-up of the publications, regarding the group of Lab 2, where it also made an evaluation, and whose objective of this evaluation, was to establish the non-inferiority of laparoscopy, in comparison with laparotomy, for recurrence, the results show that the surgical statisfication of endometrial cancer, can be performed through laparoscopy, with small differences in recurrence rates, look, 1.14 was really minimal, at the evaluation at 3 years. In conclusion, regarding minima invasion versus open surgery, the controlled trials of minima invasion surgery, show the following oncological results, they showed non-inferiority in hospital stay, shorter, a decrease of blood loss, pain and perioperative morbidity, compared to open surgery, and minima invasion surgery, is the preferred surgery for early stage disease, where the uterus, at the time of surgery, can come out intact, with good security. For that, we would have to analyze some subgroups, and in this we have obese women, in this analysis of Lab 2, in reference to patients with obesity, obese women have a higher surgical risk, and a lower risk of metastatic disease, and the body mass index was associated with mortality, in all causes, but not properly, as for the specific disease. Also, in that same analysis of Lab 2, where the subgroup was done with respect to the age, if they were older or younger than 60 years, and with and without metastasis, in relationship with the body mass index, we saw a conversion estimate of being higher, or it was present, actually, in the four groups, and this was associated with the PMI. So, what happens with the voluminous uterus, or with those uterus that have a large volume, or a large tumor, whether it is because of the size, as such, if there is a low probability of extracting it through the vagina, or especially for those women that are menopausal, or premenopausal, or those that did not have any babies, well, it could be taken out to a smaller incision, than the one that could be done with a labarotomy, and extract it, but over here, we would have to make the question of whether it is adequate. Maybe it can be done with a good security, and also those that have large uterus, of course, make it difficult when we are going to mobilize the patient in the surgery field. So, you can perform a safe surgery in that voluminous uterus, well, you can do it, but we have to consider the center management, in order to perform those resections in those voluminous uterus, and here, I'm talking about the laparotomy. For large lesions, where there can be some inflammation to the serous layer, with relationship to this publication, we could avoid the use of manipulators, because there's a higher risk of perforation of the uterus, and a risk of dissemination of the tumor. Also, the morcellation, and that is something that is already known, regarding the danger that there are, or the risks that there are, when you do the uterine morcellation, and these are very well documented, that they have to be avoided, due to the contamination that there can be, at the level of the intraperitoneal level, and if it's the mesenchymal, seromatosis tumors, and those are the ones that you... that we should take into consideration, and there are already articles that have made publications, regarding the mechanism that the manipulator has, with the tumor fragmentation, and especially at the endometrial level, and that there can be some dissemination, through the alpinges, but also, and as we mentioned, in the voluminous uterus, it's not recommended, especially in those, that have infiltration to the serous layer, there can be perforations, and there can be dissemination of the same. The use of uterine manipulator, in this article of recent publication, was associated with worse oncological results, in patients with endometrial cancer, confined to their uterus, and if we look at the first graph, look at the non-use of manipulator, versus use of manipulator, there is a statistically significant difference, in terms of oncological results, in terms of disease-free survival, not so in global survival, but having a very important consideration, and more in this last publication, regarding the use of uterine manipulator. Conclusions regarding the use of uterine manipulator, there are discordant data, in terms of whether the uterine manipulator, increases the risk of recurrence, and the use of uterine manipulator, was associated with a higher percentage, of positive peritoneal cytology, but this, in the clinical character, becomes uncertain, since the washes are not incorporated, within the FIGO certification, but in some publications, they should, or recommend, that they should be taken into account, to normalize the adjuvant behavior, of these patients. Regarding cytoreduction, as we had mentioned, in some of the points, the extra uterine disease, the recommendations for surgery, we should take into account, the location of the metastasis, the probability, of bringing a patient with cytoreduction, and complete, the retrospective series, and we see here the graph above, where they have reported better results, observed in patients, who are subject to primary treatment, but above all, when they are taken to a complete cytoreduction. It would be useless, to do a partial cytoreduction, with a, to leave a disease, an R2, that for sure, does not have an oncologically, adequate result. Regarding primary treatment, and at the same point, advanced disease, in stage 3 and 4, it is recommended, if cytoreduction is achieved, without residual disease, this is the recommendation, this is the point, if the disease is eradicated, it can be safely treated, the patients, with parotomy. Regarding the recommendations, of the ESGO, the initial surgery recommendation, in disease, with stages 3 and 4, where the cytoreduction is complete, and is feasible, with an acceptable morbidity, should be done. Many will opt, and will think, it can be done by minimally invasive surgery, but take into account, that when there is an advanced disease, the risk of potential intraperitoneal dissemination, therefore, it would not be the best recommendation. And the points to take home, open surgery, I already talked about laparotomy, it is still the treatment standard, in endometrial cancer, and minimally invasive hysterectomy, show oncological results, not inferior, compared to open surgery, there are disconcerting data, regarding the use of uterine manipulators, and increase the risk of recurrence, but have been associated, with higher percentages of positive peritoneal cytology. The recommendations, regarding the American guides, as European, from last year, establish a preference of initial surgery, in complete cytoreduction, if feasible, and with acceptable morbidity. And mentioning Professor Katie Blake, regarding the world of oncological surgery, biology is the king, the selection of cases is the queen, and I refer, to the characteristic, or tumor biology, to the clinical stage, and the surgical techniques and maneuvers, are the princes and princesses, open surgery, minimally invasive surgery, sometimes they also want to replace, tumor biology, and the clinical stage, but then they come back, because it really should not be like that, you always have to take into consideration, that the primordial, the fundamental, and the king and the queen, are still tumor biology, and the selection of cases. Again, thanking Dr. Audrey Zunoda, Dr. René Pareja, for the invitation, thank you very much for being attentive, in this presentation, thank you very much, friends, colleagues, and this sentence for my friends, René and Audrey, that suits you very well, try to be so great, that everyone wants to reach you, and be so humble, that everyone wants to be with you, that's how my dear friends are, thank you very much. Okay, thank you, Dr. Isla, great concepts, we have to think a lot about changing our practices, or changing them, or at least making some adaptations, regarding what you just told us, so let's start with our survey, our participants, talking about that, looking at cancer surgery, all the options are correct, except one, please, Mark, in your answer. Okay, okay. Don't be lazy. Participate in the poll, please. Bueno, bueno, por favor. Participen y contesten. Lots of questions for this presentation. Almost there. Okay, we're closing the poll now. Just a second. Okay. Well, it says here. David, how are you, my friend? Hello, dear friend. In patients with an important body mass index, more than 35-40, without vaginal anatomy to remove a large uterus of about 12 centimeters, what do you think about doing it all by peroscopy and, in the end, removing the specimen by a low transverse incision made only for this purpose? Yes, I think it is an option to perform this type of embroidery, especially in those patients who have a very high body mass index. Performing it by minimally invasive surgery, either robotic or peroscopic, is much more accessible. The vision is much better. I think I would totally agree to do it by minimally invasive surgery, to do an extraction of the piece in a low incision. And I think it has very good results. The impact on the difference in the size of the wounds is significant. So, I totally agree to do it. Use some kind of containment device, perhaps a large endovag or something like that? Yes, and protect the wall. Especially when extracting it, try to manipulate the uterus as little as possible and put a device to cover the wall. I don't want to mention any commercial brand, but those who protect and have certain rings could protect and make a good extraction of the piece and with great security. Would you say that perhaps the uterine volume is the main indication of performing a laparotomy? Well, that's one of the... To do it, and I mentioned it during the use of the uterine manipulator, those voluminous uterus that have very large tumors, and especially those that are in the background, using the uterine manipulator has the consequence, at the time of mobilizing it, there are risks, risk of perforation. This obviously increases the perforation of the uterus, the dissemination of cells at the peritoneal level. And the other, obviously the extraction. If I have a large uterus, but probably a lesion confined to a small uterus, that I can perform it with great security, here would be the indication. I think it would be one, more than the size of the uterus, the tumor volume, which I will generally know by image study, either by magnetic resonance, by ultrasound, which will tell us if it is really going to be the candidata. Another is those that are not, that have contraindications to perform minimally invasive surgery, either due to the cardiopulmonary characteristics, or that it has an impossibility to place the patient in a position with the legs separated, in a very forced position, which can be done for a long time in that position. I think these are the main contraindications to carry it to minimally invasive surgery. Does the conduct of auxiliary therapies change when there is uterine perforation? This is almost homologous to what happens in ovaries when the tumor breaks. Yes, I think the discussion here is very particular. There are many colleagues here who are experts on the same topic. I would say that we should take some other conduct and above all know what the form of perforation was. Obviously see the histological type, the characteristic of the tumor, to decide if we are really going to do, and we are going to give an abjuvant treatment. It is not the same, for example, a uterus that was perforated with a very small lesion, without infovascular permission. In those cases, I think there is no problem. It could probably be left under surveillance, but that perforation with a voluminous tumor that has infovascular permission and that we are probably in the disjunctive, will it give an abjuvant treatment, yes or no? Well, here I think we could decide maybe yes. Why? Because there was a uterine perforation, because the probability of cellular dissemination becomes a little higher. So, it is to characterize well the disease, the size, permeation, tumor volume, but also consider a lot of that to change the conduct between giving it or not giving it. Perfect. We are going to continue now with the schedule, but if you could help answer questions and answers, because there are many, many very interesting questions. Okay, so let's thank you again, Dr. Isla, for your excellent presentation. Thank you so much. So, our next presentation will be Dr. Paulino with up-to-date systemic therapy for endometrial cancer. So, he will aid us in understanding… We have Dr. Paulino who is going to tell us the lines for the treatment of this cancer and he is also going to tell us the new forms of immunotherapy and how this is articulated with traditional management. Thank you. Hello, everyone. My name is Eduardo Paulino. I am a clinical oncologist in Rio de Janeiro at the National Cancer Institute and Oncology at DOHR. And I am going to talk to you today about the updates we have in the system, in the systemic management of endometrial cancer. These are my conflicts of interest. The goal is to review this update of the systemic management of endometrial cancer, focusing on the inhibitors of mTOR and its combinations, hormonal therapy and its combinations, inhibitors of EGFR, MEK, MET and anti-R2, anti-angiogenic with special attention in immunotherapy. I am going to talk a little bit about the recent data of inhibitors of XPO1 and some future generations. We know that endometrial cancer is generally diagnosed in an initial stage and these patients are highly curable with surgeries, with or without auxiliary management. The problem is when these patients have recurrent disease or are already diagnosed in stage 4, where survival is much lower, just 17% in 5 years. So why do we need new drugs? First of all, as I said, survival is small, 17% for metastatic or recurrent disease. And we know that chemotherapy seems to have already exhausted the palliative stage, as I will show later. We are bringing our chemotherapy scheme, our first palliative line, already to the auxiliary stage in some cases. And well, what will we do after this chemotherapy? We are better understanding the molecular pathways. Talking a little bit about the first line, we saw in the GOG-209 that compared Carbotaxol with the triple scheme of GOG-177. And in this study, 209 of Carboplatin and Paclitaxel was not inferior to the triple scheme and with a better toxicity profile. So it would be Carboplatin and Paclitaxel as a first-line management. But what do we have of chemotherapy after that first line? We saw the results and we have several studies of stage 2 in monotherapy, where we see very regular response rates of 0% to 15% of free survival and progression of 3 to 4 months and a general survival of 9 to 10 months. These data are corroborated by the phase 3 studies that we have in this recurring scenario. For example, the XAB-PILONA study versus Doxorubicin and Paclitaxel, and the SOPTEC study that compared Soptarellin and Doxorubicin. And in these studies, we find that the response rates for chemotherapy in the second line forward, in monotherapy, are low response rates, low free survival and progression, a low global survival that oscillates between 10 and 12 months. What do we have again then? Starting with the inhibitors of mTOR and its combinations, inhibitors of mTOR, Everolimus, Tencirolimus, Ridaforolimus, also as a single drug, have low response rates that oscillate between 0 and 24% free survival and progression of 3 to 4 months, and a very low global survival. It seems that the combinations are more effective. Here are some combinations, as you can see, that have been effective in recent years, such as the studies of inhibitors of mTOR with hormonal therapy. The first study of Everolimus plus Letrosol showed a response rate of 32% and it seemed that the patients who used metformin with comitant had a response rate of 56%. However, the combination of these three drugs in a later phase 2 study did not corroborate these findings and recently we had a study that compared Everolimus with Letrosol versus acetate of megestrol with tamoxifen. In this study, we saw a response rate of approximately 22%. Unfortunately, the study did not reach the level of utility in the population as a whole, but perhaps it showed that in those populations not previously treated, there is an interesting response rate of 47% for Everolimus and Letrosol and a free survival and progression of 28 months. We have other ways to inhibit mTOR, such as this drug that has been recently tested in Vicetucertib, which inhibits both mK1 and mTOR2. This study, Victoria, Vicetucertib, associated with Anastazol, was compared with Anastazol to immunotherapy and we had a gain in terms of survival, survival, free production, response rate, response duration, and acceptable toxicity, but this drug was discontinued due to lack of efficiency in other solid tumors. Speaking now of hormonal therapy and its combinations, we can see that the hormonal handling varies a lot depending on the presence or absence of a low-degree tumor or presence of a positive hormonal receptor. In these patients, we have a slightly better response rate, but in general, the response rates are not very encouraging either. Once again, as you can see with EMTOR inhibitors, their combinations seem to have a slightly better result. As I showed you in the EMTOR combination before, and here I bring some combinations that seem to be quite promising in the case of hormone therapy. Along with the cyclin inhibitors, we have the PALEO study, which was letrozole with PABLO-C-LIB versus letrozole with placebo. And we saw that the combination brought a gain in free progression survival and a higher disease control rate. And more recently, the letrozole study with AMENBAS-C-LIB, a phase 2 study of single-arm, which was presented at the SGO this year. And Professor Constantinopoulos showed a 30% response rate with a 9.1% free progression survival rate. And this response rate did not seem to be related to the presence or absence of a hormonal receptor, if this patient was in 1st, 2nd, or 3rd grade, and if they had used previous hormone therapy. There is an interesting fact that he showed in his molecular group of those patients with P53 wild type. The response rate was 55% compared to 9% only in patients with P53 mutated. Talking a little about EGFR inhibitors, ERSTOSMEC and MET, are disappointing results for TKI inhibitors or isolated trastuzumab. But we saw that the combination of trastuzumab with carboplatin and paclitaxel in a specific subgroup, which were patients with macerose carcinoma and ERSTOS positive, this combination brought a gain in terms of response rate, free progression survival, and overall survival. And it seems that the addition of trastuzumab was mainly more effective in patients with advanced disease compared to recurrent disease. And this randomized phase 2 study placed this scheme of carboplatin and paclitaxel plus trastuzumab as a feasible scheme within the NCCN guidelines. Through the positive results that we have seen of pertuzumab and trastuzumab in breast cancer, now why not try then in endometrial cancer also in this same subgroup of patients with ERSTOS positive carcinoma. Unfortunately, in this study, the response rate was over 7%, with a disease control of approximately 37%. It is then, when combining pertuzumab and trastuzumab with chemotherapy, the results are better, as we saw in the trastuzumab study that I already showed you. Speaking now of the anti-angiogenic, again, regardless of whether it is TKI or monoclonal antibody, in the case of babisizumab, the response rates for its use in chemotherapy are not very encouraging. The response rate is 0 to 18% and the survival rate is free of progression of 2 to 6 months, and a global survival rate ranging from 5 to 19 months. We have two first-line randomized phase 2 studies. The first study is the GOG86P, a study of three pregnancies that compared the historical control of GOG209, 9-carboplatinum, paclitaxel, and babisizumab, followed by babisizumab, carbotaxol, plus tensirolimus, followed by tensirolimus, versus carboxabepilone, followed by babisizumab. In this study, the carbotaxol-babisizumab-followed-babisizumab arm gained in terms of global survival, but this comparison was made with a historical control of GOG209. In the second study, MITO2, MITO2 compared carbotaxol with or without babisizumab. In this study, although its first presentation showed a gain in free-of-progression survival, in its most recent publication, we did not see a gain in the free-of-progression survival response rate, nor in terms of global survival. In terms of immunotherapy, this group of drugs was the most effective in managing endometrial cancer. We know from the TCGA that we have four endometrial cancer molecular subgroups, and subgroups Pol E and MSI have a high mutation burden, a high expression of PD-L1. So, why not try immunotherapy for this population? We have studies with durvalumab, pembrolizumab, dorsalimab, and ablumab in this population, with a biomarker selected with a deficiency of mismatch repair enzymes. We saw response rates oscillating between 27% and 48%, and in those patients, the response rates are much lower. Some studies of this subgroup show very interesting data in those patients that were less treated previously with 0 or 1 line of treatment. We see even higher response rates, which suggests that perhaps the sooner we use these drugs in the first line, or even in the assistant, it can bring better results. And it's not just the response rate that these drugs present. We noticed that with immunotherapy, we have a very important response duration. In the case of Keynote 158, in its update, we saw that 68% of patients still maintained the response with more than three years of treatment. In the Garnett study with dorsalimab, we found that 80% of patients maintained the response for 18 months or more. We have this pre-selected biomarker, which is MSI, but 70% of patients with endometriosis are stable. How can we convert what we consider these cold tumors, which are stable tumors, into hot tumors? We can add immunotherapeutic drugs, other checkpoint inhibitors, add chemotherapy and radiotherapy to try to make the tumor more immunogenic. And that's what Keynote 146 and then Keynote 775 corroborated, which is the combination of Pembrolizumab plus Levantinib. Keynote 146, Pembrolizumab and Levantinib showed very encouraging data, which led to approval in the United States, Canada, and Australia. These data were corroborated by the Phase III study, where Pembro and Levantinib versus Doxorubicin and Paclitaxel were compared. And we had a gain there in terms of response rate, free production survival, and overall survival. More recent data shows that this benefit generation is independent of histological type, independent of the type of management previously performed. But do we need this combination for patients with MSI? 15% of the study population, Keynote 775, included patients with MSI. But we observed that this population, when handled with the combination of Pembro and Levantinib, it is true that study comparisons are sometimes not very ideal. We noticed that the response rates with anti-PD-L1 and PD-L1 isolatedly have very similar response rate and response duration, and with less toxicity methods. In the case of G3-4 toxicity compared, level 88 to 16%, and the decontinuation of handling also. A lower decontinuation of handling when the isolated immunotherapy was used for this population with MSI. We have other studies that corroborate this combination of antigenic with monotherapy, as is the case of Nivolumab and Cabozantinib compared to Nivolumab. And speaking a little about biomarkers, we know that MSS is a good marker for efficiency, for efficacy, for monotherapies. PD-L1 does not seem to be a good biomarker, and we also know that TMB-HI tumor is a good biomarker in response to immunotherapy. In this population of patients with MSS, we can have around 6 to 7% of patients with TMB-HI tumors, and they receive immunotherapy benefits as if they had MSI. So maybe there, in these patients, we can choose to investigate the TMB-HI tumor of these endometrial cancers. Another data that comes up with great importance is that patients with DMMR respond in the same way. There are patients who have methylation, only the promoter of HMLH1 seems to have a lower response rate than patients who have somatic or germinal mutations. Studies already published this year also showed another study presented in the SGO. Therefore, patients with somatic or germinal mutations probably have an even better response rate than patients with HMLH1 only. Finally, Selenexor is an Xp1 inhibitor, which is a protein that expels tumor suppressant proteins from the nucleus, as in the case of P53. So, if Xp1 is inhibited, you will keep tumor suppressant proteins within the nucleus. In this study, the study being presented in virtual ESMO this year and shortly after SGO, shows that patients treated with Carboplatin and Pactitaxel followed by Selenexor had a gain in terms of free-of-provision survival and in a subgroup analysis, this benefit was pre-established for mainly patients with a P53 wild-type, which had low interruption rates. Some future projections are that we are bringing these immunotherapy studies more and more early in first-line treatments and possibly an assistant management like these studies that you can see here. We need better biomarkers and we have to think about what we are going to do next if patients fail the immunotherapy, as we are bringing these processes more and more early. What will we do after our own immunotherapy? Without a doubt, we need more investment. By comparing, for example, endometrial cancer with the investments in uterine collar cancer and ovarian cancer, we can see that the investment is much smaller and that there was no increase compared to 2013 and 2018. What we saw was that there was an increase in uterine and ovarian collar cancer and this is directly related to a smaller number of studies in endometrial cancer and also directly related to the number of approved drugs. We see a much smaller number of drugs for endometrial cancer compared to ovarian cancer. So, I conclude that we are really experiencing great achievements in the systemic management of endometrial cancer. Immunotherapy has been boosting the efficiency of this treatment and that this molecular knowledge is really taking endometrial cancer management to a higher level. Thank you very much for your attention. Thank you. Thank you, Dr. Paulino. Congratulations. You are a brilliant police officer, as always. That was very, very impressive. Lots of studies and lots of molecules here. So, we will begin the Q&A portion with a poll for the attendees. Okay. Regarding hormonal treatment of patients with endometrial cancer, what is... Regarding hormonal treatment of patients with endometrial cancer, what is... Please respond. We have some questions already provided by the Kim audience. Okay, come on, come on, don't be shy, you have to answer, almost there, okay, so low grade disease and hormone. and I'm really excited to listen to this presentation because I think it's a very important topic. Remember to use the question and answer feature so that you can see us well in this. Well, thank you very much to everyone, I want to thank you, to the IGS-CRASE, these interactive updates of the selected topics in genealogy and I also want to thank you. And it's an honor for me to participate in this. Also, we have to look at this revolutionary moment that is happening and look at the molecular classification and the implications of therapies. I have to show here my interest subjects, which you can see on the screen. Apparently there is a huge increase in the incidence of cancer and mortality in the endometrium and they are very common, as we can see in our high-income countries, that there are some factors that have to be considered, the population, you have to look at the age and other factors. So we see that obesity is global, more than 20% today in Latin America and they are obese and approximately 58% have overweight. And so we from low-income countries with limited access to treatment have to prepare for this increasing incidence. Endometrial cancer has two subgroups that have been established according to this model that we see here, type 1, where 70% of cases generally have a high expression of the hormonal part, while type 2, which are negative for hormonal receptors and are of a difficult prognosis. So this division has also guided this treatment and these decisions that are made with respect to the treatment to follow. On the one hand, we have hormonal therapies and on the other hand chemotherapy. Here, the main issue is that behind this division, there were some data, for example, in type 1 of BOPAN, it is associated with mutations, that is, we see here R1, Decartet, R1, and we also see here type 2. And why, then, is there this mutation for those type 2 tumors and approximately 25% of those serous cancers, we see that we have this implication. We see here the BOPAN distribution, so on this horizon, it is time to have a new classification. So in 2013, this study suggested an integral genomic characterization of this endometrium carcinoma. We see here the metastasis and here the MSI with a fairly high mutation rate in this parasystem. Around 15 to 20% of these cancers are associated with this deficiency that we see here. We also see here that the mutations of K1, 3K are associated. And K5 is characterized by extensive variations and a low mutation rate of C53 with progesterone. So, the first conclusion that we can come to here is that there are some extremes in terms of the prognosis from less than or greater than. So, for example, here we see if less or greater treatment is needed, respectively. There are different groups that have tried different approaches with patients. And most of all, we see that this article speaks to us about those who use NGX, followed by IMH, for these protein deficiencies, followed by P53 and imunohistamine. So, this is the promise or the proposal that is supported by the NCC guides. So, we see here that the pole is a huge producer of a good prognosis or a good prognosis with these tumors so that there are no recurrences. We see here 17 tumors. There were no recurrences or tumors, but we see that it has also been shown that the pole shows us a low frequency. There is still a lot to learn about the pole, starting with the differentiation that exists between pathogenic mutations versus non-pathogenic mutations, and the role that homological therapy plays in terms of the time it takes. So, the goal for patients with pole is the escalation of therapy. As the guides recommend, even in the absence of prospective data, and there have been some prospective trials that have been done to explore this. Moving forward, to NFIFI, we see that there is a 30% chance of an advanced disease. We see a stronger load of the disease, we see that there is a treatment with inhibitors, and that's why we need to study this a little bit more and analyze it. Different mechanisms can be the cause of this loss of immunohistochemical protein. This is an efficient tool to identify DMMR. Additionally, the mutation of the tumors in the load, we see that these biomarkers have been explored with PD-L1 in this endometrial cancer. However, patients of a single agent based on PD-L1 were able to show only a moderate response in the trials, around 3 to 13% only, if we look at the response of the patients. On the other hand, we see the use of PD-L1 for these patients who had a better response rate. For example, we see here in this trial using PD-L1, 13% of these patients with endometriosis had a response to this drug, compared to a 57% response when the MSI was used in selected patients, and the total was 158. The same thing in the Gartner trial in a cohort that was done, we see that the response rate was around 42%. In this significance increase, we see that the response rate increased with the use of these drugs in Phase II trials, PD-L1, Dormovovav, and Ameolumab. Here on this slide, we can see the comparative data in the study of the medication based on the deficiency metric, which is from a range of 26.7% to 57%. In endometrial cancer, we see that this has been very significant between MS1 and PD-L1. We see around 25% of the patients, but not between those two subgroups, and PD-L1 positive. Focusing on sensitivity and specificity, we see here that there is a sensitivity of around 92% and a specificity of 99%. It's very interesting to see that, according to some evidence, there are some issues that were seen in the year where there is a difference in the response rate depending on the mechanism that is behind the immunohistochemical part. We see the response rate in this case of 100%. According to this prospective analysis in patients in the PORTEC-3 trial, chemotherapy is less active for those patients who have this deficiency. On the other hand, it has a very significant impact on survival and recurrence in these patients. Changing the issue here a little bit to understand the 10% around all those patients with endometrial cancer, 25% of them have these tumors. We see here the survival curves with this study in the combination of trastuzumab and chemotherapy, where there was a clear progression of survival, which was predominantly found in stage 3 and 4, the tumors compared to that recurrent population. This progression of survival was predominantly found in these patients and was demonstrated again in the updated analysis that was carried out. More importantly, there is still a clear benefit in general survival when we see that these patients are positive, especially in advanced stage tumors. Well, here we also see the hormonal therapies, which are the therapies that make the initial goal. We see here the progression response for survival. These data give us some basis to decide what therapy to follow. For example, here with unique agents, P1,3K, and here the cyclin inhibitors. Here we see this study of the activity of amino acids and letrozole. So, the perspectives, we see that these trials have an initial goal. So, I'm here including patients based on molecular results. Here we see an example of 3064-GOK with patients who are in this metric, showing the deficiency of MDMA, here with the combination of chemotherapy, and here chemotherapy as a unique treatment. Here we see these studies, and also the one called rainbow. So, with this I finish. I want to thank you for your presence and also thank you for your attention. I will be very happy to answer your questions. Thank you very much. Well, again, thank you very much from Brazil, Dr. Noviera Rodríguez, because this was an enriching talk and it was such a challenge to be able to articulate all these things that we, surgeons, think as scientists or as basic sciences of clinical practices. And the introduction of these profiles, when it has been slow, it seems to me that now, at least here, it is much better. And this will be the present and future of our topic. So, let's start our Q&A session after we do this survey to our participants. So, about the biomarkers that affect endometrial cancer therapy today, what is the option that is incorrect? Please answer A, B, C, or D. Okay, don't be shy. Don't be shy. It will end at 8.40pm. What time is it Marta? It's 8.40pm, not 8.37pm. We have 5 minutes left. Select patients for immunotherapy. Well, here it says that this is excellent for immunotherapy. Let's see. Go ahead doctor. Good morning everyone. It's a great honor for me to be here. Thank you very much Fernando. Thank you for being here with me. We are together here. Thank you very much for this opportunity. It was a very interesting talk. Yes, it was a very interesting talk. It was for us surgeons. We see with great interest what is happening in science and how that translates into clinical practice. So, the implementation of these molecular profiles in our low-income countries, this has been really slow. For example, in Chile, I believe, it must be similar in other Latin American countries, because this determination is quite expensive, but the chemistry for the proteins is quite easy. So, how have you implemented this in your practice? Or what would be your recommendation? That is a very important point for patients who are in low-income countries. But the positive aspect here, Fernando, is that most of the markers can be checked with immunologists. All patients who have endometrial cancer can do these stability studies. And the positive side, or the winning aspect, is that this is the way to select patients. We don't need PMB for most patients. Dr. Darwin has shown us that 5% to 6% of stable patients may have PMB, but we do this for most patients. So, the sensitivity for this stability using immunochemistry is around 95%. So, this is very positive. At least in Brazil, it's available in most public health hospitals. So, I think that's the positive point. Well, the other issue is that it's quite expensive. It's around $300 here in Brazil, but the price will probably go down. So, maybe we'll have access and we can fight to have that access, because that will change a very well-defined prognosis. So, we consider this very important for our patients. Well, here we have two questions that are very similar. One from Audrey and the other from Fernando Malú, which has to do with the importance of molecular profiles when we surgeons finish the surgery. What should we ask of the pathologists? The special markers, because it's not a conventional or morphological form, the biopsy. So, what should we commonly ask of these morphological biopsies? What markers? Well, the decision to use this in the classification will depend on the availability of the resources and how multidisciplinary this is. So, if it's available, I think we should do it to all patients with POLE at the beginning, because even in those cases of cancer of stage one or three, there are guidelines. These patients should be tested for stability and also for proteins. So, this is the promise guide that is in the NCDN and the guide that can help define the treatment even at the time of diagnosis. And very important, only 5% of patients with endometrial cancer, the risk of life is 70% in these patients who have endometrial cancer. So, it's very important to do this test focusing on cancer prevention. And what about HER2? HER2 is present in around 30% of serious patients, but also in cancer patients and in patients with Sentinel. Now that we have these new therapies, maybe we can increase the progression. And also, in this test of stage two, the surveillance showed that there was a gain in the survival results. But here, especially in these low-income countries, this becomes a problem because these positive data, first it was for stage three patients. So, for all serious patients, I would say that this is ideal. Jorge Holguin from Venezuela is greeting us all saying that it's a fascinating conference and asks if it's possible that maybe in the future these molecular studies are done with biopsy before surgery. Would that change the result in any way, especially for us surgeons? Well, I hope so. We have so many trials that are being carried out now in terms of medical oncology, trying to scale up the treatment. For example, if you have the inflammation of the patient, which is a patient mutated in pol, then maybe this surgery is in order. But these trials are now doing the classification of those favorable, intermediate, and unfavorable patients. So, the patients go to conventional therapy, if it's stage one, and that's how it scales up without immunotherapy. I think that's what these trials help with to scale up the treatment. Yes, and here they also ask about the use of some other markers, like Vicatanin and L1-CAMP. Yes, these are very good biomarkers. For example, if the patient expresses more than 10% of L1-CAMP, then the patient is at high or intermediate risk. So, now we have some data, but it includes the patients to stratify them according to this measurement. And for those patients who are L1-CAMP, then they are classified as unfavorable and they go to external radiotherapy versus conventional treatments. So, the data is already out there, but when it's decided, I think this is going to balance this with the decoupling of the medication. So, now, for example, we know that those biomarkers have a prognosis and the data from the perspective to guarantee that it can be decoupled, we have to say that we don't have it yet. Well, we have a couple more questions, but we have to keep on with the agenda. Thank you very much, Angelica. If you can please answer them internally. But I see that many pathologists are very interested in your presentation. So, please make sure to answer those questions. So, thank you again, Dr. Nogueira-Rodriguez. No, thank you. I'm going to answer all the questions. Our next presentation will be Dr. Simmons, controversies in radiation, oncology, for endometrial cancer. I have no conflict of interest. So the number of known prognostic factors for individual therapy is 1. There are many factors that this includes the state of the tumor, the degree, the osteological type, the depth of the myometrial invasion, the lymphovascular invasion, the age. So how do we take current evidence into account, the knowledge of these risk factors, and apply it to our daily decision-making? How can we really handle this evidence to apply it to this decision-making? We have to take into account that this does not affect general survival. So here we have some definitions. When we are talking about external beam radiotherapy, we are talking about radiotherapy to the pelvis and or the pelvic ganglions, and the parahortic ganglions, depending on what is given. And these patients receive five weeks of daily fractions. And then we are talking about vaginal brachytherapy, or VBT brachytherapy. It's given as standard fractions. So this treatment of chemotherapy is complementary. So what is this? We'll start way back when with PORTEC-1, which was a radiotherapy study for early endometrial carcinoma. They included patients of stage 1, grade 2 or 3, grade 1 and 2, with more than 60% of the invasion. The patients received EBRT radiotherapy, or randomized treatment. And they received a 15-year follow-up in 2011. The main difference in the study was that the recurrence was really positively affected with the use of this treatment, but there was no difference in the final result. What they did find on multivariant analysis was patients who were older than 60 years with grade 3. And the final conclusion of the study is that EBRT does not have an effect in general for general survival in this particular group of patients. Then we have PORTEC-2, which talks about vaginal brachytherapy versus the EBRT in the same group of patients. They included patients with an invasion of less than 50% and grade 3, more than 50% of invasion and grade 1 or 2, and they all had already won the ILA. And as we can see in the graph, in the general result, we have our three criteria and there really was no significant difference. Here we are illustrating that there is no difference in general survival. So, a very important result was toxicity in patients with EBRT, which is obviously beneficial when you need to use radiotherapy in this group. So, the general conclusion, following PORTEC-1 and PORTEC-2, is that EBRT alone is the choice treatment for these patients. Then we continue with PORTEC-3. We are looking at the other side of the spectrum of patients with high risk in groups of stage 1 and 2 and patients for stage 3 in the disease. And here we were looking at chemotherapy versus radiotherapy. So, the groups that were included were cell 1A, serocycliara 1BG3, stage 2 patients and stage 3 patients. So, there was chemotherapy with 50 mg platelets in week 1 and week 4, followed by adjuvant chemotherapy with CARBO and placitaxel versus radiotherapy alone. The results of stage 1 and stage 2 patients have no difference in general survival, but there was a noticeable difference in general survival in more than 10% in stage 3 patients and more than 10% for this group. Here we are just demonstrating the results in a graph of the pelvic radiotherapy in stage 3 patients. So, pelvic radiotherapy is, in itself, enough for patients with high risk of stage 1 and stage 2 in this study. And chemotherapy and radiotherapy for stage 3, high risk, what is unknown is the benefit for patients with serous carcinoma. And it showed an improved general survival for the combination for a small group of 100 patients, which are very few to differentiate by stage. So, what do we know at the end of all this, after stage 3, is that stage 3 patients have a better result with chemotherapy, the correct chemotherapy and the ideal combination of chemotherapy and radiotherapy. Although some also receive only radiotherapy, unfortunately, these benefits are not yet known, but wait, there is more to the story. So, there were equivalent studies that were carried out in the United States, the GOG-249 in phase 3 study with patients in the early stage with high risk and high intermediate, endometrial cancer, but there was no difference in overall survival in these two subgroups. So, pelvic radiotherapy was equivalent to chemotherapy, there were three cycles of CARBO and TAXOL, equivalent to general survival, but the local failure rate was reduced. So, the conclusion from the study, from the authors of the study is that pelvic radiotherapy is the way to handle it with less toxicity. And here, I would say that based on PORTEC-3, if you have a serous carcinoma, you could possibly consider adding chemotherapy along with radiotherapy. Then came the GOG-258, which was published the same year as PORTEC-3, and here we saw that adjuvant chemotherapy plus radiation for local advanced endometrial chemotherapy. So, the difference from PORTEC-3 is that radiotherapy was not analyzed by itself, and here they did not find any difference between chemo and radiotherapy, but a high incidence of vaginal recurrence and recurrence of pelvic or paraortic ganglions. So, for locally advanced stage endometrial cancer, if you have an advanced stage local endometrial carcinoma, chemotherapy may be enough, but chemotherapy plus radiotherapy improves local failure rates. But, as clinical oncologists, we look at survival and also local results as a whole. So, what would I do for the only group of patients that I would offer adjuvant chemotherapy? It would be stage 3A and B, high-degree, anyone with ganglion involvement. So, I think there is no controversy in my mind that all patients with endometrial carcinoma could benefit from chemotherapy and radiotherapy if they are above a low degree of 1A in endometrial cancer. The next developments for radiotherapy, we are currently preparing the PORTEC-4A study, which are patients in stage 1A. And now we are becoming medical oncologists because we are looking at how to integrate the profile into our decision-making regarding appropriate therapy. And this study is providing patients with poly mutation, those who are deficient in MMRD. If so, they fall into an intermediate group and may also be in another variable group if they are CTNNV1 wild type or with CTNNV1 mutation or not. And then we have the high-risk group that has the T53 mutation evidence and L1-CAM expression or a certain expression greater than 10%. So, these patients will then be randomized to receive self-specific therapy. If you fall in the favorable group, which group will receive the vaginal brachiotherapy and which will receive the external beam radiotherapy, and so we are going to define the percentage of the different cohorts that will be assigned to each one. So, my conclusions, we have to consider, number one, the resources for those of you who work in a region without access to radiotherapy at all. Clearly, patients will be observed in the early stage and for those who have an intermediate or high risk, it can be considered a carboplatin and placentaxel and for very high-risk patients, it could also be the case. And then for those who have access to surgery and some access to radiotherapy, they can potentially observe patients with low risk and be in an early stage. And according to the PORTEC-2 study, they can use VAULT for those in stage 1 with intermediate or high risk. You can give EBRT for patients in the early stage and who are at high risk, according to the PORTEC-3 and the GOG-249. There is no very long waiting list. You can give chemotherapy and VAULT for patients at high risk in stage 3, if you have it, that would be the last group. This could also be the case that there is a long waiting list for radiotherapy. If we have the situation in which we have access to surgery and radiotherapy without a waiting list, then my suggestion for you is to follow the evidence and choose your team. And I follow the European guidelines and for a high-risk patient, I would offer chemotherapy and radiotherapy together immediately. Thank you very much for your attention and I look forward to answering questions. Thank you very much, Dr. Simmons. As we would say in England, lovely presentation. So, in a way, what you have shown us is a story about radiotherapy in endometrial cancer and also the circulation with the molecular hyperfiling of this cancer. So, let's start our questions and answers with a survey for the attendees, please. Regarding the treatment or treatment in patients with endometrial cancer, what is the truth? There is only one option. Please select. okay don't get lazy we're almost done okay let's see let's see that's it says here it says here study for all that's the one that got the most votes so how is today going Dr. Simmons? very good, I would like to be there in person it's a little bit warmer than England yes, I'm going to England next week okay, so molecules again see how molecules are integrating on the adjuvant we talked about that before with Dr. Nogueira here's a question for you about Porte 4a do you think it's already even before the results even before the results it's no longer valid in time because the Rainbow Study already offers adjuvant chemotherapy for all those patients with these mutations that's the problem with these studies it takes a long time to design them it takes a long time to start and convince the people to do it to do it and give the result the science behind it was already valid so I think there's no doubt that many people are already using this information in their clinics P53 would be very unlikely not to give that therapy and although I don't like to criticize my colleagues I think it's interesting that Porte 4a didn't offer chemotherapy for those high-risk patients because that's the way we do it there are always some differences in design between America American and European studies and I think in Europe we count less about chemotherapy than maybe in the United States and maybe they use less radiotherapy and they could use it a little more but I think it's not unreasonable the science is real and we should look at those high-risk characteristics if there is pathology that can provide it and thus make a decision about what to give to the patient but before the results are there it doesn't have a ready point so in the daily clinic they use MMR or P53 P53, what a shame to define the radiation treatment decisions radiotherapy, no I think it's because we have both available modalities it's MMR is the Porte 4a study tells you not to give chemotherapy to patients but in reality we are not brave enough to leave it out for stage 3 patients because in practice that's what we do and a P53 patient normally a P53 patient has something more and it would be considered high risk and it would be a combination treatment so I have to say that in general coming from a European and South African scenario we use a lot of radiotherapy and that's what I can say I understand if we also do it we have good availability of radiation in Chile but that's not the main thing or the real thing for many of the countries so the last slide was really brilliant because you have to use what you have in the context with the tumors you receive in your office so I would really argue strongly that people consider some type of radiotherapy for intermediate and high risk patients because the local recurrence is a very undesirable result so if you don't have a good follow up like we do in Africa or maybe you yourself in some places in South America the patient comes back with their recurrence yes, the recurrence in endometrial cancer is obviously terrible very good so I think that's all for now, we have to continue with our next presentation again Dr. Simos thank you very much, it was wonderful and now we are going to continue with our final presentation of our great friend Dr. Julian Fili from Argentina who is going to present the technical aspects of endometrial cancer surgery welcome Julian I want to tell you that I don't have any conflict of interest specific for this talk this talk is oriented to talk about those technical aspects of endometrial cancer that are interesting and I have divided it in two parts at the beginning we are going to talk about some theoretical concepts in relation to the discussion that can be raised in terms of the approach and some small areas of discussion and in the second part we are going to talk about more technical aspects and more practical concepts in relation to the use of gangliosentinella to the technique of gangliosentinella and to the surgery itself and to finish with some final recommendations in relation to how to do how to organize also based on the practice and the experience and the theory of how to do the statification of endometrial cancer the first point that I want to raise in relation to the approach and bring this topic about if it is safe to use the minimally invasive way for the treatment of endometrial cancer the most modern study with which we count and it is one of the two studies that we have prospective is the LAST TRIAL in this study the approach was compared for the treatment of endometrial carcinoma that when comparing patients that were operated by the open way versus the minimally invasive way the results in terms oncological were similar and these results of the LAST TRIAL were also demonstrated in a previous study well known by all which is the SHIOSHIP LAB 2 there is one thing that you can tell me and that is reasonable is that in these studies the vast majority of the patients correspond to histologies of low grade and initial stages in this later study where it was grouped to the patients of SHIOSHIP LAB 2 that had histology unfavorable and grade 3 it was also possible to demonstrate that the survival was the same comparing the approaches that's why today the most practical explanation is that we can all make the effort to evolve, to have the best training so that the patients that have endometrial carcinoma are certified and treated by a minimally invasive way always obviously having the repairs in relation to what is oncological surgery in general and following this line of thought I want to raise as an area of ​​discussion the use of uterine manipulator in the treatment of endometrial cancer when we do a minimally invasive surgery either robotic or laparoscopic we generally rely a lot on uterine manipulation by vaginal guide and this is an area that one believed quite closed there is an article with retrospective evidence of the year 2017 in which when comparing patients who had used versus patients who had not used the manipulator one was quite calm because it showed us that both the rate of relapses and the places of residues did not show differences in the group of patients more recently a study was published Spanish of which also retrospectively when comparing patients in which it had been used versus patients who had not used the manipulator one can see a higher rate of mortality in patients in which they had not used the manipulator I think none of the two studies can be 100% conclusive, obviously by the bias that represents retrospective studies in patients that one does not know well why the type of tumor was used or in what conditions the uterine manipulator was used but I think one should be cautious especially in those patients with high-risk carcinomas or voluminous tumors where the manipulator can generate dissemination and not even talk about what is uterine perforation I think that uterine perforation can have a role in what is tumor dissemination that's why when placing the manipulator or when manipulatingulating the uterus in the course of surgery one must have certain precautions as we talked about before certain repairs that make what is oncological surgery in general to try to offer the patient the best results Well, the last point I want to raise as an area of ​​discussion is the use of peritoneal cytology within what is endometrial cancer surgery what we know does not constitute a state as such has an uncertain role but if in patients who have neoplasmic cells in the peritoneal cavity the prognosis is worse I think this scenario of uncertainty in relation to peritoneal cytology has caused to fall into disuse what one sees is that it can help to the global assessment of the patient especially in patients of high risk I think the practical recommendation is not to stop doing it, not to forget although it does not have an important role today, it can help in the long run when we have to need some more data in the patient We then move on to what is the second part of the talk which is one of the most practical concepts in relation to the use of the sentinel ganglion and the specific surgical technique the use of sentinel ganglion in the process of stagification has become today practically in a standard a less invasive practice that lowers complications later and that does not act in detriment of the detection capacity of metastasis since we are seeing that one is going to detect more metastasis and this can be explained at the expense of the appearance of low-volume metastasis micrometastasis and ITC it is important to have clear the technique polish the technique to be able to have success in the detection of it let's see now quickly some concepts based on the surgical technique the first step within what is the global surgical strategy is to evaluate the abdomen obviously to discard advanced disease or carcinomatosis and then do a good evaluation of the pelvis especially to discard adherence or large pelvic blockages that delay or delay the injection of the dye and the subsequent search for sentinel ganglion and this is because the vast majority of dyes, including indocyanin green tend to fade after a while the second step and probably the key to success is the injection of the dye for endometrial cancer it is seen, it is studied that the cervical injection is fundamental and this injection must be in hour 3 and hour 9, well lateral the more lateral one does it the dye drains more towards each hemipelvis and be dedicated especially in what is the superficial injection use a suitable needle I recommend this Raquidia 21G injection needle it must be a needle that is long enough and hard enough for one to be able to handle the injection well in addition to making a correct injection it is important to have a good timing, that is, do the injection and as one is doing it, see how the dye is draining by transillumination or see by transperitoneal how it is draining towards each hemipelvis, even already have located a place where one can detect the ganglion, this timing also goes in relation to the mechanisms that have the dyes or the times that each dye has in reaching the ganglion and then smoking, spread, stain the field and avoid a correct location of the first sentinel ganglion the other aspect surgical based on the technique is that when one is looking the sentinel must be very delicate in terms of dissection, especially the dissection of the lymphatic from the neck of the uterus to the side in the pelvis because if one at the beginning makes a section of all those channels those are cut and the dye really does not reach the sentinel ganglion on the other hand I think it is also important when we do the sentinel ganglion identify the vascular structures nervous anatomical when we do a lymphadenectomy at least have them identified without cutting the channels not to affect the lymphatic drainage and have the lymphedema for that but to avoid the injuries of the large structures of the pelvis finally and also as part of a correct technique in relation to the whole process of sentinel ganglion the extraction of sentinel ganglion is that the specimens that you get through the technique extract them through some care process inside a bag or inside a glove after the identification and extraction of the sentinel ganglion surgery continues doing a hysterectomy of which for endometrium carcinoma corresponds to a hysterectomy Fiverr 1 or a class A hysterectomy which the section of the uterine vessels is at the level of the arrival of the uterine in the uterus in the isthmus unlike what are the radical hysterectomies that are used for carcinoma of the uterine neck where the section of the pedicle and the uterine artery are at the level of the cross with the ureter for Fiverr 2 or in its origin which is Fiverr 3 radical hysterectomies for endometrium carcinoma are superlative to very few cases and always the discussion is if when the endometrium carcinoma compromises the neck one must do a radical hysterectomy but it is a longer discussion and there are studies that show that there would be no difference between doing a radical or a Fiverr 1 hysterectomy be careful once completed the hysterectomy what is the section the colpotomy do it carefully and also what is the extraction of the piece by the vagina that is in a careful way in the sense of not disseminate or that there is no spread of what is the content either of the vagina or the same that can come out from the neck of the uterus to the abdominal cavity. The next is the role of freezing the intraoperative biopsy at the time that one can complete the hysterectomy and this is given because normally prior to the use of the sentinel angle in many centers we rely on intraoperative freezing as risk definition at that time in high or low risk patients to be able to complete or not do or not a systematic lymphoanectomy when we did not sentinel. I think that today is the era of what is the sentinel angle what is the intraoperative biopsy has fallen quite in disuse and we can only use it or it can give us a panorama in the sense that we have not detected one of the two sentinels or none of the two sentinels and in this way decide or define the risk factors intraoperative to complete or not the lymphoanectomy on the side where we do not find the sentinel. In this way the intraoperative biopsy what it does to us is to lower the amount of unnecessary lymphoanectomies Well, finally and to finish we make a brief summary of everything and a recommendation, the surgery of the endometrium carcinoma begins with a careful inspection of the cavity especially of the pelvis make a peritoneal cytology in all your patients, pay more attention in those patients who have a high degree, a favorable cytology, remember that this can give us a better global assessment of the patient surgery continues injecting the dye for the realization of the sentinel gang remember to do a cervical injection careful, subepithelial well superficial, accompanying a deep injection if you want, but normally the success of the detection of the sentinel gang is in the superficial injection very careful and after doing the injection one can place the manipulator, remember that the uterine manipulator also for endometrium cancer can have some effect especially in large tumors high risk tumors, then make a careful placement also a careful manipulation during the surgery and make all your greatest effort to advance, know and have as fast as possible the curve of experience for what is the sentinel gang technique it is not necessary to have endocyanin, it is not necessary to have the best chambers, you can do it with methylene blue, you can do it with isosulfan blue, with patent blue the important thing is to be able to do it to be able to train, because it is a technique that is less invasive, it does not mean that it is easier but it requires a training curve many times greater than what is a lymphadenectomy complete the surgery with a stereotomy, this is a stereotomy pivar 1 or class A be careful obviously in the extraction of the uterus, in the colpotomy, in the normal repairs of an oncological surgery to avoid what is the dissemination use the biopsy for freezing as a criterion to define risk factors intraoperatory when you have doubts about doing or not the lymphadenectomy, but above all when you do the sentinel gang technique use intraoperatory freezing when you have not found any of the two gangs, obviously complete the lymphadenectomy according to the criteria of lymphatic mapping and the criteria of high or low rivers that you use in your center I thank you very much for having listened to me, I hope this talk has been useful and I am at your disposal for the questions you think are necessary thank you all okay thank you Julian excellent presentation and beautiful thank you Julian excellent presentation how important is to recognize all these tips to standardize the procedure so let's start with questions and answers this is the last survey for the attendees so some of the clinical aspects are important in surgery please choose the incorrect answer incorrect incorrect all of you 271 participants right now you can answer don't be shy this is the last one la ultima a couple of seconds left let's participate Okay, let's see the answers. Okay, let's see the answers. Most people said that when the ganglion is not detected on one side, the recommendation is to look at the opposite side. Congratulations for your presentation. How important it is to standardize this technique, and I think you were one of the pioneers in our region of Latin America. What do you think about this? How has this technique been introduced in our daily practice with patients with endometriosis? Good morning, Fernando. Thank you all for the presentations. Thank you for inviting me to be here today. I hope I have been at the level of the tremendous presentations that you had before. By the way, my friend. With respect to the specific question, until recently, even today, people ask us to talk about whether this is a standard, how it becomes a standard, and I think that the assessment or saying that a technique is a standard depends on the place where you work, the region, the hospital. Let's say, little by little, one thinks that this has to be the standard. We saw the presentation of Dr. Mariani, and there are many explanations, and there is evidence, and practice shows us that it is not only a less invasive method, but that it offers a better or greater diagnostic return than what you are looking for for endometriosis. That is, to have a better standardization, to have the patient correctly seen in terms of his prognosis, and also that it helps us a lot for what is chauvancy. And this goes hand in hand with not only the technique I was showing, which is the technique of finding the most representative ganglion, but the study of that ganglion accompanies a whole process that makes us diagnose more, and a little of what we are seeing, which will increase the lymphatic metastasis rate that we are diagnosing, compared to what we did before, at the expense of micrometastasis and etc. But the idea is to promote the use and development of this technique, which, although it seems a less invasive thing, requires its learning curve and its ability to know how to do it well. Without a doubt, Julián. We have commented on it because this is a topic that both of us are very passionate about, and we have been, so to speak, pioneers in our respective settings. In that sense, there is a question from Ignacio Chávez, who says, Who has adopted endometriosis? Has everyone validated their local negative phases with sentinella and systematic lymphadenectomy at the same time? And that has to do a little with the curve. In my particular case, I did the first sentinella in Bulba in 2006 with blue. Today, of course, I work with indocerin green, but there are people who do not have access to that. So, what would you tell them to start doing this technique, to be able to validate themselves in their centers? First, to be able to do only the sentinella angle it is essential to do the own validation, the evaluation of each one. And this is achieved by comparing the sentinella angle with the rest of the lymphadenectomy. What one cannot have are false negatives, that is, that the sentinella angle is negative and the lymphadenectomy is positive. That on the one hand. And then, on the other hand, obviously being in constant contact and asking, I believe that Dr. Perrota just mentioned the pathological study. The sentinella angle, unlike the lymphadenectomy, must have a more exhaustive pathological study. It must go to ultrastaging first, and if the ultrastaging is negative, it must go to chemical immunity with cytokelatin A7 to detect the ITC. So, the pathologists must also be standardized with the fact that it is the protocol for the sentinella angle, which sometimes that part is not very widespread. Exactly. Otherwise, it is useless. So, again, the importance of cooperating with our pathologists, our pathologist anatomists, to tell them, this particular angle, I want you to study it like this, because if not, the surgical effort that I am making to change my practice towards the sentinella angle to offer the benefits of the technique, is useless. If we don't do ultrastaging, it's useless. They also ask here if you would only use the sentinella angle or the sentinella angle technique in cases of patients with high-risk tumors such as light cell carcinoma. That is, if you feel comfortable using that technique in that type of patients. Well, nowadays it is also seen that for high-risk, there are even prospective studies, there is the SHRED trial, which is a prospective study for high-risk patients, that when one is settled on the technique, has validated it, and its detection rate is good, one can really move on and can trust in the detection of the sentinella angle. There was a question there too, which was well done before. Obviously, one does not stay calm when one does not find it. And there you have to make the decision to do the lymphoanectomy on that side, because a high-risk patient cannot stay with one hemiplegia or both without investigating the ganglion state. I think that aspect is important. But yes, when you have already made your learning curve and in the place where you work, the technique is installed and you trust the technique, one can move on, including high-risk patients too. Without a doubt. How important is the standardization of the technique. That is, that our technique is always the same, is what allows us to offer the results, the results that are validable and that preserve the oncological benefit of endometrial cancer surgery. Many of the questions that are both in the questions and answers section and in the Zoom chat, refer to that. How deep is the injection? How many ml? That is something that is quite standard. In my case, and we have talked about it many times, the one who injects the green indociline is always the same assistant. It is always the same, at the same speed, while the others are looking from above. Everything has a perfect timing. A good question is, when to re-inject? Well, in that regard, I also believe that it is part of what is the global technique and the success between a good detection rate. My recommendation is to do the re-injection, the patient is injecting and is looking directly behind his lighting. When you see that the colorant has not passed correctly parallel to the luteal neck and there is no channel that one can see, it is time to be calm and do a re-injection again. And I think that many times it will be the situation that one finds the ganglion on both sides. And let me say one thing, Fernando, based on what you were telling about the technique, I think that the technique itself has been standardized. Things that I just showed in the videos are about expert recommendations. I see today articles based on standardized technique for ganglion, things that should be done, things that one should not do. And I think it is the difference between the first jobs that one saw where the ganglion was detected less than half the time. Nowadays, if one standardizes with this and obviously puts in its learning curve and does the necessary cases, the detection rate can be very high. Well, we have the last questions left. Let's see here. If there is any variation in the technique when methyl blue is used versus indocyanin green? Well, that is quite easy to answer. Indocyanin green made it even easier for us. With a high cost. There are already second-generation cameras and they are also integrated into the robot. But if you don't have indocyanin green, you can use methyl blue, as long as, as we previously mentioned, it makes a curve and sees its eventual negative false. Yes, based on this, what we just showed in terms of timing, injection site, needle type, even the colorant volume, it's all similar. Obviously, indocyanin green made it much easier to visualize the fact of continuing a surgery after it doesn't have any blue stains. I think in that sense, it improves the issue. Obviously, one has to say in a webinar, which is also Latin American, that many times the transition from one technology to another or from one technique to another requires an effort in terms of technology and getting the colorant, which is not easy everywhere. That's right. Well, let's close our session today because there are still many questions left, but time has run out. We had a great time. Thank you again, Dr. Di Wilmi. Nice to see you as usual. I would also like to thank all of our assistants around the world. I just read that we have an assistant from Kazakhstan, which is wonderful. And finally, to JTCS for considering me to moderate this webinar. It has been a real honor to moderate it. And the recording of today's session will be available on the portal next week. So please remember to join us next Saturday for the next session of the webinar series on ovarian cancer. Muchas gracias nuevamente.

endometrial cancer surgery

uterine manipulators

peritoneal cytology

intraoperative freezing biopsies

sentinel lymph node mapping

abdomen and pelvis inspection

dye injection technique

lymphatic channels

sample bag or glove

sentinel lymph node extraction

less invasive surgery

improved staging

ongoing training

collaboration with pathologists

surgical strategy