Welcome everyone to the Interactive Updates on Selection. So, we have a great session today. Now, it is my honor to introduce the presenters of today's webinar, Andrea Mariani, from the United States, Davila, from Mexico, Dr. Eduardo Paulino, from Brazil, Dr. Angélica Nogueira Rodrigues, from Brazil as well, and Dr. Hanna Simons, from the United Kingdom, and finally, Dr. Julia D. Guilme, from Argentina. The recording of this webinar will be available on the IGSS education portal IGSS, and you can submit your questions through the IGSS education portal, and you can send your questions through the Q&A session. After that, we will read the questions at the end of the presentation, and we will try to answer as many questions as possible. Well, to start our program today, we will see the presentation called Lymphatic Cancer Assessment. And who better than Dr. Andrea Mariani to address this topic? She is a specialist on this topic, Endometrial Cancer Management. So, thank you, thank you everyone. Thank you for your attention. Thank you, Renée, for inviting me to this talk. I'm Dr. Mariani, from Mayo Clinic, Rochester, Minnesota. I've been studying endometrial cancer for the last two decades. Specifically, I studied the patterns of lymphatic propagation and the role of lymphadenectomy in endometrial cancer. At the beginning of this century, we identified a population of patients, about a third of endometrial cancer patients, with an insignificant risk of positive pelvic nodules, based on histology, grain, myometrial invasion, and tumor diameter. And we call it the Mayo Criterion of Lymphadenectomy. Using frozen section and all these parameters, we could decide which patients needed full pelvic and paraortic lymphadenectomy against those patients that did not need lymphadenectomy. But then, in 2013, our friend and colleague from Memorial Sloan-Kettering, Nadim Abulstum, came to Mayo Clinic and taught us how to do centenal lymph nodes. And so, we started to notice a rapid decrease in the performance of the pelvic and paraortic lymphadenectomy. But how did we get here? And how were we convinced to do centenal lymph nodes? To answer these questions, we must first ask the following question. Is lymphadenectomy therapeutic in endometrial cancer? And if we look at the Cochrane Library in 2017, a review tells us that with or without lymphadenectomy, there is no difference in oncological outbreaks and there is no greater risk of lymphedema and cystic lymphangioma. And what about prospective studies? And even there, we do not see any significant clinical therapeutic effect. In particular, there are randomized studies and we can say that pelvic lymphadenectomy does not improve survival in low and medium risk endometrial cancer. But what about the paraortic area? In fact, we know from the May data that 62% of patients with positive nodules have some kind of tumor dissemination in the paraortic area. Is there any occult dissemination in patients with a tumor apparently confined to the skin? And the answer is yes. This Japanese study, in which they monitored 15 patients with positive and negative pelvic paraortic, but when they did an ultrastaging, they found that 73% of these patients had an occult tumor in the paraortic area. Therefore, we can conclude that there is tumor dissemination in the paraortic area in the vast majority of patients with positive lymph nodes. And so, if we look at the therapeutic role of the paraortic lymphadenectomy and we look at the retrospective data, we find mixed messages in the literature. Some articles say that it is therapeutic, that paraortic lymphadenectomy is therapeutic and others say it is not. This is the most famous article about the paraortic lymphadenectomy and the therapeutic role. It is retrospective, comparing only pelvic versus pelvic and paraortic in patients with some type of high-risk characteristics and yes, paraortic lymphadenectomy. According to this article, it improved clinical oncological outcomes. But it is retrospective. We have some differences in the administration of chemotherapy between the group. And it is very important to mention that no patient received chemotherapy and radiation combined after surgery. And only a small group was serous. This is a 2018 meta-analysis focusing on retrospective studies comparing the pelvic patient versus that pelvic and paraortic patient. In this meta-analysis, they say that the paraortic lymphadenectomy improves overall survival. However, when we look at adjuvant therapy, the article they included in this meta-analysis, only one of the articles, had a combined approach. Most of the others have adjuvant therapy, only chemotherapy or radiotherapy. And with respect to the combined approach, both chemotherapy and radiation, given the retrospectives, we see that the pelvic patient with pelvic lymphadenectomy only had better results, but received more adjuvant multimodal therapy. Therefore, what they concluded is that adjuvant multimodal therapy, chemotherapy and radiation, is more important than the extension of lymphadenectomy. Without adjuvant multimodal therapy, the therapeutic effect of lymphadenectomy is more significant. And there may be a therapeutic role of lymphadenectomy, but it is less significant clinically, if they receive radiation and chemotherapy. And what about the clinical data about the therapeutic role of paraortic lymphadenectomy? This is an article from 2000, retrospective, and we observe that the paraortic lymphadenectomy improves survival, but the patients received, even here, only adjuvant radiation, without combined chemotherapy. In fact, in the most recent data from Mayo Clinic, focusing only on patients with positive paraortic nodules, we see that the most important predictors of survival are grain, esthology and adjuvant therapy. In particular, patients who receive chemotherapy and combined radiation have better results. So, what we conclude is that patients with positive paraortic nodules, chemotherapy and radiation, regardless, improve the outcome. Biology is the most important predictor of the prognosis, and the extension of the paraortic lymphadenectomy did not predict the outcome. In particular, patients with endometrial cancer and no endometriosis had a bad prognosis, regardless of adjuvant therapy, and died because of distant residues. This is a similar paper from Korea, in patients with positive nodules, where some patients received adjuvant pelvic radiation, some received a combination of pelvic radiation and chemotherapy. And even here, in retrospect, the paraortic lymphadenectomy significantly reduces the parasitic residue in all groups. However, it makes a difference in survival only in the radiotherapy group, but not in the patients who received the combined therapy. Therefore, the administration of chemotherapy and combined radiation reduces the importance of the potential therapeutic effect of the lymphadenectomy. In this paper, patients with endometriosis had a bad outcome, regardless of the extension of the paraortic lymphadenectomy. And this is a similar paper from China, from the Mayo Clinic, where patients with endometrial cancer do not have good results, and most of the residues are hematogenic or peritoneal. This means that the battle is lost at a distance, not in the pelvic and paraortic area. So, regarding the therapeutic role of the lymphadenectomy, the lymphadenectomy, like radiation and local treatment, can reduce local failure, but it is less likely to improve survival. And patients with positive nodules are more likely to die from distant residues. And with a combination of therapeutic therapy, radiation and chemotherapy, the oncological outcomes are usually better, and the clinical significance of the potential therapeutic role of the lymphadenectomy is reduced. Now let's talk about the endometrial cancer centennial nodules. Does it work? This is a meta-analysis that tells us that, from a diagnostic point of view, it works very well. But do we have perspective data? Yes. This is the FIRES study, and here it works very well from a diagnostic point of view. And yes, it works very well even in a perspective study with a high-risk focus, degree 3 and serous. So what we can conclude from the literature is that the centennial nodule is a superior diagnostic tool to the lymphadenectomy. But what about oncological outcomes? Are they compromised? Here we have a paper from Canada that compares the centennial nodules with the lymphadenectomy, and we see that the centennial nodule has less residue on the pelvic side wall because with the centennial nodule we can identify more unusual metastasis locations. So the centennial nodule is superior to the lymphadenectomy to identify lymphatic metastasis, and we can see less lymphatic residues. In the Fruitful collaboration with Memorial, we compare a series of studies from May with lymphadenectomy and systematic paraortic against a more recent series from Memorial only with centennial nodules. And in recent years we publish almost one article per year. In total, five articles observing the oncological and diagnostic outcomes. And we conclude that the centennial nodule versus lymphadenectomy has similar diagnostic outcomes we find patients with positive nodules but with similar oncological outcomes. And this is mostly a retrospective analysis, but this is what we concluded. Now, let's answer this question. Would you complete the lymphadenectomy pelvic and paraortic if the centennial nodules were positive or if they were positive in the frozen section? We have an article about this, which makes a comparison of patients with positive nodules from Mayo Clinic with complete lymphadenectomy versus centennial nodules only from Memorial. There were some differences in the number of patients with chemotherapy versus external face radiotherapy and, as expected, patients with lymphadenectomy had more lymph nodes removed. But what we observed is that if you treat patients with complete lymphadenectomy compared to centennial nodules, there was no significant difference in the free-of-progression survival because of specific or lymphatic residue. The oncological outcomes and predictors of overall survival were mainly related to tumor biology and if we gave chemotherapy and radiation after surgery. In the multivariate analysis, the most important predictors were degree and histology. Therefore, we concluded that a combination of chemotherapy and radiation in patients with positive nodules may improve the outcomes, but biology is the most important predictor of bad oncological outcomes. We concluded, finally, that if there are no voluminous nodules, lymphadenectomy is unlikely to provide an important therapeutic contribution since these patients are already identified with centennial nodules and received a combination and although the risk of paraortic progression has been 3.7 times higher in the cohort of centennial nodules, the rates of isolated paraortic progression were similar. This finding implies that many paraortic progressions are associated with distant concomitant dissemination. Therefore, my answer to the question is that we do not take patients back to lymphadenectomy if the patients have a positive centennial nodule. We do not complete lymphadenectomy until the lymph nodes are microscopically positive. So, what is missing? We are missing large prospective data on oncological outcomes in large prospective data of patients treated This is the prospective study that we are doing in collaboration with Omemorian. Thank you very much. Very well. What happens then? When we look at patients with isolated paraortic and we do ultrastaging on negative pelvic nodes, we actually find that 30% of patients with isolated paraortic had, in fact, occult pelvic dissemination. Therefore, isolated paraortic dissemination is a rare event and even more rare if we do ultrastaging of pelvic lymph nodes. Thank you for your attention. I'm sorry. We had a sound issue. Thank you for your attention. Thank you, Dr. Mariani. This was an excellent presentation. Remember to present your questions. Let's start with the questions and answers part. Let's do a little poll. One of the following elements are not part of my criteria. Please select one. Thank you for joining. Keep voting, keep voting. Okay, we are now closing the poll. under two centimeters in absence of... Can you mention that, Dr. Mariani? Yes, it's a really... One of the things that is really crazy is the lymphobascular space and the fact that it's not part of the Mayo criteria is the involvement of the lymphobascular space and the fact that it's home to the lymphobascular space but it's hard to know that during the frozen season and the criteria are related to the Mayo criteria so that's why it wasn't included in the criteria and from that, the inter-observation, the diagnosis of the involvement of the lymphobascular space is often not something that agrees with the tumor diameter. Just another comment about the tumor diameter. It's a very important parameter and it's relatively easy to simply measure during the surgery and that's why it was an important factor within the Mayo criteria. Thank you very much. Yes, we have some questions here. The isolated tumors of the cancerous cells, isolated if we treat with chemotherapy, these cells? These isolated. Well, thank you very much for the question. We're seeing that more and more of these cancerous cells, isolated, through a parameter, it's more likely, according to the data we know at the moment, but we're still working on the data on some of the things that aren't clear yet but what we know so far is that these cells, these isolated cells, they become important cells. There are risk factors at the uterine level. For example, if we have a very aggressive tumor, if we have, for example, an endometrium cancer, a serious cancer, a lymphobascular infection and also isolated cancerous cells, it becomes much more like a patient with positive ganglions. So, in this way, we assume this case as being a patient with positive ganglions. So, we can do it with chemotherapy or radiation chemotherapy and radiotherapy. However, what is not clear yet is the meaning of isolated cancerous cells. In patients who don't have risk factors in the uterus. So, for example, patients with endometriosis, with isolated tumor cells, without lymphobascular invasion, with isolated cells, degree 1, degree 2. We don't know the meaning of this so far. Personally, I still know that there are some colleagues in the literature who say that it's not all about that. But my answer at this moment is that we still don't know. Because it may still be a microscopic disease that can grow. In this way, we still need to have more data on this. But so far, so far, both in May or according to what I know in the Memorial, we decided to treat these patients with observation. And we do close monitoring. So, again, the meaning depends on whether there are risk factors in the uterus. We have another question from the audience, from Dr. Paulo Gimenez, who was from Chile and now he works in Canada, and he says, do you recommend extended field radiation to the patients with sentinel ganglions, positive pelvic? What kind of treatment do you recommend as a co-adjuvant? It's a fantastic question. It focuses especially on the same discussion about lymphadenectomy. Because I think about it more, and lymphadenectomy has been done for a long time. And both radiation and lymphadenectomy, from the therapist's point of view, is that there is a therapeutic value. So, what we see in our comparison with Memorial, for example, is that the lymphadenectomy, the parasitic one, it can reduce the amount of parasitic residue if it's a local treatment. There's a disease there. And sometimes it's taken away and it can reduce the amount of parasitic residue. But people die due to this disease, right? So, in general, the decision to do extended field radiation is a decision if we want to prevent parasitic residue. But it's not something probable according to the data we have so far to give you an answer. So, it's a decision. It's not something probable according to the data we have so far to give you more survival information. So, currently, we don't do this routinely, but it's certainly a reasonable focus if we want to reduce the potential role that parasitic residue may have. Do you know if there is, for example, a prospective study on this topic? Paralytic lymphadenectomy at an international level? He said he doesn't know if there is a prospective study that focuses on paralytic lymphadenectomy or paralytic radiation. If you know there is a study, please feel free to tell us. Feel free not to exclude this study. Please, if there is a study, please tell us. But as far as I know, there is none that focuses on paralytic lymphadenectomy or paralytic radiation. And also, the problem is that to do a study is very difficult because we must focus on patients with positive nodes. This is something limited. According to the majority of patients with positive nodes, these patients are at high risk. The vast majority, okay? I don't want to say that all patients are at high risk, but most patients are at high risk. In this way, it is much more likely that they die due to this residue. In this way, it is very complicated to have the exact figures for this, because the patients who will most likely benefit from the local treatment are probably patients with grade 1 tumors. In this way, probably, if we did a patient study with positive nodes, with grade 1 endometriosis, we may have some good results, but it is difficult to get these figures to carry out this study. Well, Dr. Fernando, thank you very much. And I have a much more philosophical question for you. They say here, how is it that the paradigm can be changed, the paradigm of doing pelvic and paralytic lymphadenectomy to only do the mapping of the ganglions and the centinella? What led to this change? Because if this could be done in a large hospital center, maybe we could do it too. What was it that gave this spark to make this change? He says that, first of all, we started to analyze the data, and the data that we had then, they gave us a clue that there could be a potential to reduce the residue, but it was not enough to convince these data about the survival results, they were not convincing. But after that, what convinced us was the case of our friend, for example, our friend Adiman Brusto, he came to the clinic and we started to see, in this way, our data together, and we decided to take this risk. In this way, we put together the data of historical retrospective with the data of the Memorial, which were beginning to be ganglion and centinella, and in this way, we divided this data, we looked at this data, we sat down as friends, we trusted at a certain point, it was evident that the data would go in a certain direction. What convinced me then were the data, but also the case of a friend. And what is important is this, the collaboration, this was the main thing, this was what helped us. Now it is much easier to communicate, for example, from Chile to the United States, live and be able to share things as we are doing today, this is fantastic. In this way, thank you very much, Dr. Mariani, and we have many other questions, but we must continue with the program. Thank you very much, it is an honor to be with you. In this way, our next speaker will be Dr. David Isla, an excellent friend of mine, with the presentation that if there is still a role in laparotomy, in endometrial cancer, nowadays we know that the treatment is the same for everyone, and where do we put laparotomy? Please. It is a great pleasure to greet dear friends and colleagues. Thank you very much for the invitation, Dr. Audrey Zonalda, Dr. Renée Pareja, dear friends, colleagues and companions. With the theme that I will present, if there is a role for laparotomy in endometrial cancer, my name is David Isla Ortiz, I am an oncologist, I am an endometriologist, my name is David Isla Ortiz, I am an oncologist, I am the head of the Department of Gynecological Oncology at the National Institute of Cancer in Mexico. Let's look at these graphs, which are very interesting and make a stratification referring to low, medium and high income countries, where we see that the incidence has increased up to 10 times worldwide, with a growing trend of post-traumatic stress disorder. This is reflected in a change in lifestyle and a greater prevalence of risk factors that are associated with this disease, obesity, physical inactivity, which has been seen as a very large reflection in new generations. In this publication, we also see some graphs that are very important, where the incidence has increased over time, and if we look at the different years, in 2002, at 6.5% and in 2011, more than 30%. This has also been seen as logarithmic growth so far. And in the next graph, if we look at it, how the graph shows a decrease between days of hospitalization, open surgery, compared to one day of laparoscopic surgery. It has decreased, and I think that now, even more so, with the use of less radical procedures, such as ganglion, for example, this hospitalization will probably be much more reflected, and with a much more important decrease. And there are, or are carried out, procedures that are part of the staging of endometrial cancer, especially those of medium and high risk, which is bilateral pelvic lymphadenectomy and paraortic lymphadenectomy. And the sentinel ganglion, this biopsy that is being carried out for the identification of the first ganglionary relay is of extreme importance, since it has been able to reduce the risk of complications triggered or produced by this lymphadenectomy. Also, the procedures of radical sterectomy, which are carried out, especially, not only involves at the level of the cervical stroma, which has already been seen, that the same or with only one type A sterectomy can be carried out, but not in those that are voluminous tumors, for example, and that have incipient appearance in terms of extension and direction to the parameter, a radical sterectomy can be carried out, especially to have safe margins and make an adequate assessment of the parameters. And in those young patients that we usually see both the tumor and the stage and the patient's characteristics, an ovarian preservation could be done. Returning to the question, is there still a role for laparotomy in endometrial cancer? Well, considering that the standard is laparotomy, and what is around this laparotomy are the different approaches, minimally invasive approaches robotic, but also vaginal approaches that become less responsive to trauma. This has a direct impact on the patient with better results, both in the trans-operator and post-operator, and a much faster incorporation in everyday activities. In addition, obviously, the combination of these minimally invasive procedures with vaginal approach. But laparotomy, and going back to the subject, what could be the indication? Well, those patients who are not candidates for laparoscopy, either by physical conditions to maintain a very forced position during laparoscopy, such as the very forced position of the Ellenburg train, or because of the placement of the legs that do not have this capacity, or because of the functional state, or because of problems, both cardiological and pulmonary, and also because of the disease, large uterus, or large tumors, or because of the simple use of the manipulator, which in some cases may cause a deleterious effect, also in those stages 2, 3, and 4, and it may be convenient to perform a cytoreduction. Laparotomy may be probably the best indication, and in those cases, when there is a tumor residue, laparotomy becomes very important for the treatment of these patients. But let's look at the first point, the non-candidates for laparoscopy. Taking into consideration that minimally invasive surgery versus minimally open, is an access route. Many studies were carried out, both retrospective and prospective, and in this review by Cochrane, for example, it talks about the estimated blood loss, and laparoscopy was associated with a large decrease, and it is significantly important in comparison to laparotomy. A point in favor of laparoscopy, referring to global survival and residual survival, in the first point, there was a non-significant increase in the risk of death from laparoscopy versus open, and referring to residual survival, there was not statistically a difference in the risk of disease residues. In this evaluation, referring to quality of life, also a point in favor of laparoscopy, is that the patients with laparoscopy reported much higher scores, and that were significant in the functional evaluation of the patients. In the post-operative of minimally invasive surgery, referring to the guides of the European NCCNO, this is what was presented, and it is a recommendation that surgery could be of both open and minimally invasive surgery, with certain benefits different from the last approach. This in the publications of Cochrane's systematic review. In this prospective study of Lab 2, where the main goal was the comparison of laparoscopy versus laparotomy to study the surgical staging of uterine cancer, where the results of the surgical staging of endometrial cancer can be done through laparoscopy, without an intraoperative increase of injuries, with less complications post-operative, and a much shorter hospitalization. In monitoring the publications referring to the Lab 2 group, where an evaluation was also made, where the purpose of this evaluation was to establish the non-inferiority of laparoscopy compared to laparotomy, in this way to see the residue. The results show that the surgical staging of endometrial cancer can be done through laparoscopy, with small differences in residue rate, see 1.14. It was truly minimal, with an evaluation 3 years ago. Referring to minimally invasive surgery versus open surgery, the controlled studies of minimally invasive surgery, they show the following oncological results. They showed a non-inferiority in hospitalization, it was shorter, a decrease in blood loss, pain, and perioperative morbidity, in cooperation with open surgery. And minimally invasive surgery is the preferred surgery for a disease with a previous stage, where the uterus, at the time of surgery, it can be intact, the uterus. It can be intact and with good security, and for that we should analyze some subgroups. And for that we have obese women, in this study of Lab 2, referring to patients with obesity. Obese women, they have a higher surgical risk and a lower risk of metastatic diseases, for example. And the IMC was associated with mortality in all causes, but not specifically for the specific disease. Also, in the same analysis of Lab 2, where subgroups were made, I apologize if I have audio problems, I apologize, okay? Following, without metastatic disease, in relation to the IMC, an estimated conversion risk was observed, and it was higher, or was more present in the four groups, and this is associated with the body mass index. What happens with large uterus? Or with those uterus that have a large volume, or a large tumor? And this, due to the same size, there is a low probability of being extracted through the vaginal pathway, especially those pre- or postmenopausal patients, patients who usually have not given birth yet. So it can be difficult to extract this uterus. Many people will ask, can it be extracted through a much smaller incision, which could be done with a laparotomy and removed? But this would be a question for the gentlemen and ladies. Is it adequate? Can this be done safely? And also in those cases with large uterus, where it is difficult at the time of mobilization in the surgical field, can a safe surgery be performed in this large uterus? It can be done, yes. But, yes, considering a standard treatment to perform the resection in these large uterus, and I mean laparotomy, for large lesions suspected of infiltration into the serous layer, and referring to this article with this publication, it could then be avoided the use of manipulators, because there is a greater risk of uterine perforation, and there is also a risk of tumoral dissemination. Also the morcellation, and we already know the dangers that exist with uterine morcellation, and they are already being documented, and should be avoided due to the contamination that may exist at the intraperitoneal level, and in this way cause, whether in tumors of sarcomatosis tissue, and carcinomatosis also in the reptiles, right? The use of uterine manipulator, which we should take into account, referring to this, and there are already articles referring to this, which have published in relation to the mechanism that the manipulator has, with the tumoral fragmentation, especially at the endometrial level. And there may be some dissemination through the salpinges, that is, the fallopian tube, and also, as we mentioned, in the voluminous uterus, it is not recommended, especially in those that have filtration, even in the serouse, because there may be perforations or cause dissemination of the same. The use of uterine manipulator, in this article that was recently published, was associated with worse oncological results, in patients with endometrial cancer, confined to the uterus, and if we look at the first chart, we can see, then, the non-use of manipulator versus the use of manipulator, there is a statistically significant difference in terms of oncological results, in terms of survival and disease-free. Not in survival at a global level, right? But yes, having a very important consideration, even more so in this last publication regarding the use of uterine manipulator. Well, conclusions regarding the use of uterine manipulator, there are data that disagree, right, regarding whether it increases the level of recidivism, and the use of the manipulator was associated with a higher percentage of positive peritoneal zytology. But this, in clinical terms, becomes somewhat uncertain, since the manipulators are not included in the FIGO study, but some publications do recommend that it should be taken into consideration for the non-adjuvant behavior of these patients. Regarding cytoreduction, as we had commented on some of the points, the extra-uterine disease, in the recommendations for surgery, we should take into consideration the location of the metastasis, the probability of taking a patient with complete cytoreduction, the retrospective series, and we see here the graph above, where they reported better results observed in patients who were subjected to primary treatments, but especially when they are taken to a complete cytoreduction. It would be useless to simply do a partial cytoreduction and leave the disease, an R2, a partial cytoreduction and leave the disease, an R2 that certainly does not have an oncologically adequate result. Regarding primary treatment, and at the same time, cytoreduction for advanced disease in stages 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, patients can be treated safely, they can be treated with laparotomy. Regarding the recommendations of ESCO, ESTRO and the guidelines of the LCCN in 2021, the initial surgery recommendation in diseases with stages 3 and 4, where cytoreduction is complete and feasible, with acceptable morbidity, should it be done, then? Many will choose and think, right? Can it be done through minimally invasive surgery, but taking into account that when there is an advanced disease, there is a potential risk of intraperitoneal propagation. Therefore, it would not be the best recommendation. And the points for us to take home are the following, open surgery, and I'm talking about laparotomy, which is still the standard treatment for endometrial cancer, and minimally invasive hysterectomy show non-inferior oncological results compared to open surgery. There are discordant data on the use of uterine manipulators if the risk of recidivism increases, but they have been associated with higher percentages of positive peritoneal cytology. Recommendations relating to the American and European guidelines from last year establish a preference for initial surgeries in complete cytoreduction, if it is feasible and with acceptable morbidity. And mentioning Professor Cade Blake about the world of oncological surgery, biology is the king, the selection of cases is the queen. And I mean the characteristic of tumor biology at 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 at the clinical stage. But then they go back because it really shouldn't be like that. It should always be considered and the important, the fundamental, the king and the queen are still tumor biology and the selection of cases. I want to thank again Dr. Odris Onoda and Dr. René Parerra for this invitation. Thank you very much for paying attention and I read this sentence to my friends René and Odris which fits them very well, right? 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 concept in your presentation. We have to think a lot before changing the presentation or fully switching them to endoscopic. So let's begin with the Q&A portion. We're going to start with our poll. If our participants are correct in terms of endometrial cancer surgery, all the options are correct, except one of them is in the poll. One of them is wrong. Please state your answer in the poll. Okay, don't be lazy. Participate in the poll, please. Lots of questions. Almost there, almost there. Okay, we're closing the poll now. Just a second. It says here, by individual trials comparing minimally invasive surgery versus open surgery, you know what I mean? So, we're going to start with the questions for Dr. Isla. We have a question here. I'll help with that. Okay, a question in Spanish, let's see the questions in Spanish. David, hello, Mr. David, how are you? Mr. David responds, in patients with IMC, important, with more than 35 or 40, without vaginal anatomy to remove a large uterus, approximately 12 centimeters, what is your opinion on doing all this with a laparoscopy, and in the end, remove with a low transversal incision, made only for this purpose? Dr. Isla says yes. It's an option to do this type of approach, especially in these patients, in patients who have a high mass index. Doing it through minimally invasive surgery, be it robotics or laparoscopy, is much more accessible. The effect is much clearer. I think I would completely agree to do it by minimal invasion, to remove the piece through a low incision. And I believe there are good results. The repercussion of the results on the difference in relation to different sizes is something significant. In this way, I completely agree to do it this way. Do you use a containment device, maybe a larger device or something like that? The doctor says yes. Protect, above all, the wall, and especially at the time of extraction, try to manipulate the least possible uterus, and put a device to be able to cover, to protect the wall. I don't want to mention any commercial brand, but yes, there are devices that protect, that have certain rings, that can protect and make a good extraction. So, in this way of the piece, and with a lot of safety, says Dr. David. Do you believe that the uterine volume is the main indication of performing a laparotomy? The volume that tells us that? Dr. David says, look, this is one of the concepts to perform. I already mentioned this during the presentation, the use of the uterine manipulator. These voluminous uterus, which have very large tumors, especially the uterus that are at the bottom. Using the uterine manipulator has a consequence at the time of mobilizing it, right? There are risks, yes, risk of perforation, and this obviously increases, to perforate the uterus, to disseminate cells at the peritoneal level. And the other would obviously be extraction. If I had a large uterus, voluminous, but probably a lesion confined to a small uterus, which I can perform very safely, and here would be the indication. I think so. More than the size of the uterus, the tumor volume, right, people? Where I will know, through imaging studies, either by magnetic resonance, by ultrasound, which will tell us if it will truly be a candidate or not. Others are those that have contraindications to perform minimally invasive surgery, either by cardiopulmonary characteristics, for example, or characteristics that show an impossibility to place the patient in a position with the legs separated, for example, a very forced position, a position that can take a long time in this position, take a long time in this position. I think these are the main contraindications to perform minimally invasive surgery. Does the adjuvant therapy behavior change when there is an uterine perforation, doctor? What happens in the ovary when the tumor breaks, right? There are prospective data, but what do you do? I think the discussion is very particular, says Dr. Davies, and we have colleagues, colleagues who are specialists on this topic, right? But I would say that, yes, we should adopt one or the other behavior, but above all, know what the perforation form was, see the histological type, see the characteristic of this tumor for this form, decide if we truly opt for an adjuvant treatment, that is, it is not the same thing, a uterus that was perforated with a very small lesion, without infovascular permeation, for example. In these cases, I think there is no problem, we could probably just leave it there, just keep an eye on it. But that perforation, for example, with a voluminous tumor that has lymphovascular permeation and that we are probably there thinking whether to give an adjuvant treatment or not, I think that in this case we could say yes, because there was a perforation of the uterus, the probability of dissemination, lymphovascular, should be higher. So, yes, characterize well, analyze well the disease, the size, the permeation, the volume of the tumor, but also take into consideration all this to be able to change the behavior between giving or not. Thank you very much, said Dr. Fernando, saying that we will continue now with the event, but please, could you help us answer questions and answers? We have a lot of questions here in the chat, okay? Thank you again, Dr. Isla, for your fantastic presentation. The next presentation will be from Dr. Paulino. He will tell us about the cancer treatment guidelines and talk about the new forms of immunotherapy and how this is linked to traditional management. Thank you. Hello, everyone. My name is Eduardo Paulino. I am a clinical oncologist here in Rio de Janeiro at the National Cancer Institute and I am an oncologist. My topic today is to talk about the updates that we have on the systemic treatment of endometrial cancer. These are my conflicts of interest. The goals, then, are to revive this update of the systemic treatment of endometrial cancer, focusing on inhibitors and their combinations, hormonal therapy and its combinations, inhibitors of EGFR, MEK, MET and anti-R2, anti-hygienic, with a special focus on immunotherapy, to talk a little about the recent data of the inhibitors of Expo1 and some future directions that I see in the future. We know that endometrial cancer is usually diagnosed in the initial stage and these patients are usually highly curable with surgeries or without adjuvant treatment. The problem is when these patients have recurrent disease and are already diagnosed in stage 4, in which the survival rate is much lower, only 17% of patients surviving in 5 years. So, why do we need new drugs? First, as I showed you, the survival rate is small, 17% for metastatic or recurrent disease. And we know that chemotherapy seems to have already exhausted the palliative scenario, as I will show in the slides later. We are bringing our chemotherapy scheme, our first palliative line, to the adjuvant scenario, sometimes. So, what are we going to do after this chemotherapy? We are also having a better understanding of the molecular pathways. So, talking a little about the first line, we saw through GEOG 209, which compared caboplatin with the GEOG 177 triplet scheme, that in this study, 209, caboplatin and pactaxel were not inferior to the triplet scheme and with a better toxicity profile. So, putting caboplatin and pactaxel as an elective treatment in the first line. What do we have from chemotherapy after this first line? We saw the results. We have several Phase II studies in monotherapy that we saw very unhappy response rates, from 0% to 15%, free 3 to 4-month survival, and a global survival of 9 to 10 months. These data are corroborated by the Phase III studies that we have in this recurrent scenario. For example, we have the study of ixadepilone versus doxorubicin and pactaxel, and the ZOPTEC study compared to zoopteriline, which is an ADC, versus doxorubicin. And in these studies, we can also see that the response rates for chemotherapy in the second line and so on, in monotherapy, are low response rates, low free survival, and a low global survival, varying from 10 to 12 months. What have we seen that is new since then? Starting with inhibitors and their combinations, inhibitors such as derulimus, tenserolimus, and ridaforalimus, also as a single drug, have low response rates, varying from 0 to 24%, free 3 to 4-month survival, and a fairly low global survival. It seems that the combinations are more effective. In this case, I brought you some combinations that have been effective in recent years, such as the studies of inhibitor inhibitors with hormone therapy. The first study of verurimus with retrosol showed a response rate of 32%, and it seemed that patients who used metformin with the inhibitor had a response rate of 56%. However, this combination of these three drugs, in a subsequent study of phase 2, did not corroborate these findings previously. And more recently, we had a study that compared verurimus with retrosol versus acetate of medestrol with tamoxifen. In this study, we saw a response rate of around 22%. Unfortunately, the study did not reach the level of activity in the population as a whole, but it showed that in those populations that were not previously treated, we had an interesting response rate of 47%, with verurimus and retrosol, and a free 3-month survival. We have other ways to try to inhibit the mToc, for example, this drug that was recently tested, the Vistucertib, inhibits both mToc1 and mToc2. In this study, the Vistucertib associated with noestrozol was compared to noestrozol in therapy. We had a gain in terms of free 3-month survival, response rate, response duration, with an acceptable toxicity. However, the development of this drug was discontinued due to the lack of effectiveness in other solid tumors. Moving now to hormonal therapy and its combinations, we can also see that hormonal treatment varies a lot depending on the presence or absence of a low-degree tumor or the presence of a positive hormonal receptor. In patients, we have slightly better response rates, but in general, the response rates are not very encouraging for me. Once again, as we have observed with hematopoietic inhibitors, their combinations seem to have a slightly better result. I showed the combination with hematopoietic inhibitors before, and here I bring some combinations that seem to be quite promising, in the case of hormone therapy, together with cyclin inhibitors. We have the Paleo study, which was letrozole with falbociclib versus letrozole with placebo, and we saw that the combination brought a free-of-progress survival rate and a higher rate of disease control. And more recently, the study of letrozole with abiamaciclib and the study of phase 2 of single-arm, which was presented at the SDO this year. Professor Constantinopoulos showed a 30% response rate with a 9.1% free-of-progress survival rate, and this response rate did not seem to be related, in fact, to the presence or absence of a hormone receptor. If the patient had level 1, level 2, or level 3, and if hormone therapy had been used previously or not. An interesting fact that he showed was exactly in the molecular subgroup, in those patients with P53 wild type, the response rate was 55%, compared to only 9% in patients with mutated P53. Speaking a little about GFR inhibitors, ER2, MEK, MET, also disappointing results for TKI inhibitors, or for isolated trastuzumab. But we saw that the combination of trastuzumab with carboplatin and Pactaxel in a specific subgroup, which were patients with carcinoma serosum and positive ER2, brought a gain in terms of response rate, free-of-progress survival rate, and global survival rate. It seems that the addition of trastuzumab was mainly more effective in patients with advanced disease, when compared to recurrent disease. This phase 2 study put this scheme of carboplatin, Pactaxel, and trastuzumab as a feasible scheme in the NCCN guideline. Through the positive results we saw of trastuzumab and pertuzumab in breast cancer, why not try it in cancer of endometrium, also in this same subgroup of patients with carcinoma serosum and positive ER2? Unfortunately, in this study, the response rate was only 7%, with disease control of approximately 37%. Who knows, maybe by combining pertuzumab and trastuzumab with chemotherapy, the results will be better, as we saw in the trastuzumab study shown earlier. Moving on to antigenics, once again, regardless of whether it is TCA or monoclonal antibody, in the case of bevacuzumab, the response rates for its use in monotherapy are not very animating. Response rate of 0% to 18%, survival rate of 2 to 6 months, and a global survival rate of 5 to 19 months. We have two randomized phase II studies in the first line. The first is the GeoGe86p study, which was a three-arm study, which compared the historical control of GeoGe209, carbopatin, pactaxel, and bevacuzumab, followed by bevacuzumab, carbitaxel plus tensirolimus, followed by tensirolimus, versus carboxypeplona, followed by bevacuzumab. In this study, the first arm, carbotaxel and bevacuzumab, followed by bev, had a gain in terms of global survival, but, once again, this comparison was made to the historical control of GeoGe209. In the second study, MITLAND2, which compared carbotaxel with or without bevacuzumab, in this study, despite its first presentation showing a gain in free survival progression, its publication, which is more recent, we did not see a gain in response rate, in free survival progression, nor in terms of global survival. Entering immunotherapy now, this group of drugs were the drugs that most demonstrated efficacy in the treatment of recidivized endometrial cancer. We know, through the BCGA, that we have four molecular subgroups of endometrial cancer, while the subgroup POI and mycosatellite instability has a high mutation rate, a high tumor mutation burden, has a high expression of PD-L1, so why not try immunotherapy for this population? And that's what was attempted. We have studies with duvalumab, tembrolizumab, endocytalimab, and also quadelumab. In this population, with a biomarker selected, with a deficiency of endometrial repair enzymes, we saw response rates ranging from 27% to 48%, and in case of proficient patients, the response rates are much lower. Some subgroup analyses of the studies show very interesting data, such as patients who were previously treated with 0 or 1 line of treatment, we saw even higher response rates, suggesting that the sooner we use these drugs, in the first line, or even in adjuvance, it can bring even more encouraging results. And it's not just the response rate that these drugs brought to us, we realize that with immunotherapy we have a very important response duration. In the case of Kynote 158, in its update, we saw 68% of patients still maintaining the response with three more years of treatment. And in the Garnier study, the Astalimab study, we saw 80% of patients maintaining the response for 18 months or more. We have this pre-selected biomarker, which is the microstatelet instability, but 70% of patients with endometrial cancer are stable. How can we transform what we consider cold tumors, which are stable tumors, into hot tumors? We can add medications, other immunotherapies, other checkpoint inhibitors, add salve therapies, add chemotherapy, radiotherapy, to try to transform this more immunogenic tumor. And that's what the study Kynote 146 and Kynote 775 corroborated, which is the combination of Pembrolizumab and Levantinib. In Kynote 146, Pembrolizumab and Levantinib showed very encouraging data, which led to approval in the United States, Canada and Australia. And these data were corroborated by the Phase III study, when we compare Pembrolizumab and Levantinib versus Doxorubicin and Pactaxel. We had a gain in terms of response rate, survival rate and global survival. More recent data show that this benefit gain is independent of the histological type, independent of the type of treatment performed previously. But do we need this combination for patients with endometrial cancer, with micro-satellite instability? 15% of the population in Professor May's study, Kynote 775, included patients with micro-satellite instability. But we observe that in this population, when treated with the combination of Pembrolizumab and Levantinib, it is true that study comparisons are sometimes not very ideal. We notice that the response rate with anti-PD-1 or PD-L1 is very similar and with less toxicity. In the case of toxicity level 3 and 4, we see that, comparing from 88% to 16%, there is also a lower discontinuation of treatment when we use isolated immunotherapy for this population with micro-satellite instability. We have other studies that corroborate this combination of antigenic with immunotherapy, in the case of Nivolumab and Cabozatinib, compared to isolated Nivolumab. And speaking a little about biomarkers, we know that micro-satellite instability is a good biomarker for effectiveness, for immunotherapies. PD-L1 does not seem to be a good biomarker. And we also know that Tumor Mutation Gordon High is a good response biomarker for immunotherapy. In this population of patients with micro-satellite instability, we can have around 6% to 7% of patients with Tumor Mutation Gordon High. They derive the same benefit from immunotherapies as if there were micro-satellite instability. So maybe in stable patients, we can opt to try to research Tumor Mutation Gordon of these endometrial cancers. Another data that has been showing a lot of importance is that patients with micro-satellite instability, not all of them respond in the same way. Those patients who have methylation only of the promoter of MLH1 seem to have a lower response than patients with somatic or germinative mutation. This was shown in this study already published this year, as it was also shown in another study presented at SDO. So patients with somatic or germinative mutation probably have an even better response than patients with only promoter methylation. Finally, Selinexo is an inhibitor of Expo-1. Expo-1 is a protein that throws tumor suppressant proteins out of the nucleus, as in the case of P53. So if you inhibit Expo-1, you keep these tumor suppressant proteins inside the nucleus. In this study, a study being presented at ESMO virtual this year and later at SDO, it shows that patients treated with Caboplatin and Pactaxel followed by Selinexo had a gain in terms of free survival and progression. In a pre-established subgroup analysis, this benefit was mainly in patients with a P53 biotype, a functioning P53, and had low rates of discontinuation. Some future directions, followed by the conclusion, we are seeing that we are bringing these immunotherapy studies more and more early, in first-line treatments and possibly in adjuvant treatments, as these studies that I show you in the table. We need better biomarkers, and we have to think about what we are going to do later if the patients fail the immunotherapy. As we are bringing it more and more early, what are we going to do after our own immunotherapy? Without a doubt, we need more investment. When we compare, for example, the cancer of endometrium, the uterine cancer, compared to the investments in cancer, in the uterine colon and the ovarian cancer, we see that the investment is much smaller, and that there was no increase compared from 2013 to 2018, what we saw was that there was an increase in the cancer of the uterine and ovarian colon. This is directly linked to a lower number of studies in endometrium cancer, and also directly related to the number of drugs that we have approved, we see a much lower number of drugs for endometrium cancer, compared, for example, to the ovarian cancer. So I conclude with you that we are really experiencing great achievements in the systemic treatment of endometrium cancer, the immunotherapy has been leveraging the effectiveness of this treatment, and that this molecular knowledge is really leading the treatment of endometrium cancer to a new level. Thank you for your presence. Wow, thank you. Thank you, Dr. Paolino, congratulations. A brilliant presentation, as always. That was very, very impressive. Lots of studies and lots of molecules here. Very interesting presentation. Many studies, many very interesting things. Let's now do the poll on hormonal treatment in patients with endometrium cancer. What is right? Can it be considered as the first line of treatment? Does it work better associated with platinum-related agents? Very well, you can answer poll number three. Okay, come on, come on, don't be shy, you have to answer. Almost there. Okay. Low-grade disease and hormonal disorders exhibit better clinical response. That was kind of easy, wasn't it? So now, let's start with the questions and answers. First, hello Eduardo, good morning. For whom would you consider hormone therapy and which is the best partner? Thank you very much for being here today and for the opportunity. It's a very, very interesting event. We have data for both types of combinations, for hormone therapy, for both types of inhibitors. I believe that, from a standard point of view, I believe that the cyclical inhibitors have a better scenario. But I believe that we need more biomarkers that are better to decide which of the two and for whom we could use these two types of inhibitors. A question about... One that is here in the chat. I think we have two questions for the survey. Can we use this first-line for a specific population in these patients who have metastatic disease? And also, is it true that it is also included in the guidelines for first-line treatment? There is another question here from Dr. Maluf. Do you believe that we could recommend hormone therapy for those patients who do not have micro-satellite instability? But what do you think? A very interesting question, Fernando. In fact, we have two Fernandos here. Because we can see that it is approved in the United States for these patients who do not have micro-satellite instability. In other words, MSI. So, there are many patients with high sensitivity to this deficiency with this type of treatment. An average of 5%. And many times we lose this 5% of patients. In a recent article about the way to measure these patients and consider those patients who are stable micro-satellitely, the answers are very interesting. 65% in some populations. And I think we could use this for this type of population subgroup. Any other questions? The majority of people who are joining us today are possibly surgeons. We have people here from Russia, India, Canada, especially from Latin America. But we are very happy because we have more than 300 people participating. This is wonderful. This is a worldwide event. Thank you very much again, Dr. And we will take a five-minute break. Remember to come back in five minutes for our next presentation, Applications for Therapy with Dr. Angélica Nogueira Rodrigues. Thank you very much. Okay. Welcome back. Thank you very much to all of you, Dr. I would like to thank GST for organizing these interactive updates on gynecological cancer in Latin America and express my gratitude for the invitation. It is an honor to be part of this presentation today. We must see this revolutionary moment for patients with endometrial cancer and I will start with an adequate clinical and molecular classification. Currently, there is an alarming rise in endometrial cancer incidence and mortality by endometrial cancer, which is several factors. Endometrial cancer is the most common gynecological cancer in high-income countries due to various factors including population, aging, and obesity. The obesity epidemic is global. Currently, more than 20% of Latin Americans are obese and approximately 58% of them are overweight. Therefore, in low-income countries with limited access to treatment, we need to prepare for this increasing incidence. Classically, endometrial cancer has been divided into two subgroups according to the Bokman model in 1.70% of cases, generally of low degree and with high expression of hormonal receptors and type 2, generally of high degree and negative for hormonal receptors and with a worse prognosis. This division, in turn, guides the systemic treatment decisions until now. On the one hand, we have hormonal therapies and, on the other hand, chemotherapy. The point is that, behind this simple division, there is a complex disease. For example, type 1 endometrial cancer is associated with a mutation in PTENK1AENPIK3K and MSI, while PT53K1AENPIK3K is associated with a mutation in PTENK1AENPIK3K. is mutating in most of the subtype 2 tumors. Approximately 25% of the cancer of the serous endometrium have an amplification of HER2. Faced with this complex scenario, it's time to have a new classification. In 2013, TCGA suggested a genomic classification of the endometrial cancer with four subtypes. Polyultramutated, MSI-hypermutated, with a high mutation rate in the genes involved in the repair system of incountability. Approximately 15% to 20% of all endometrial cancers are associated with incompatibility repair deficiency. We see here the number of copies often associated with the mutation in P10, PIK3K, and K-RAS. And the number of copies is high, characterized by extensive variation in the number of copies and low mutation rate. Frequent mutation of TP53, low expression of estrogen and progesterone receptors. The first conclusion we can come to here is that there are extreme prognoses of lower to higher risk. And we will try to indicate less or more treatment, respectively. Different groups have tested the best approach to classify the patients, and the majority agree that when available, the test should start by immunohistochemistry using EGS, followed by immunohistochemistry for protein deficient in the repair of incompatibility, followed by TP53 by immunohistochemistry. This is the proposal of Promise Group, with the support of the NCCN directors. It is considered a strong predictor of good prognosis. In TCGA, there were only 17 poly tumors, and there were no residues in this group. Subsequent studies have shown that poly has a residue, but it still has a low frequency. We still have a lot to learn about poly, including the differentiation between pathogenic and non-pathogenic mutations, and the role that immunotherapy plays for these patients. And if there is a role, when it should be used, the goal for patients with poly is decolonization therapy. Currently, as more directors recommend, even in the absence of prospective data, there are some prospective studies studying this now. Moving on to MS-ALT, MS-ALT includes approximately 30% of advanced disease cases. It presents a high load of new antigens, with a strong logic to explore the treatment with immunological checkpoint inhibitors. Different mechanisms can be the cause of MS-ALT, such as immunohistochemia, protein loss, acquired hypermethylation, somatic mutation, and germinative mutation. In addition, the tumor's mutational load and PD-L1 were explored as biomarkers for anti-PD-1 and PD-L1 drugs in endometrial cancer. However, the selection of patients for immunotherapy based on PD-L1 was able to show only a modest response in clinical studies, around 3 to 13%. Only 3 to 13% of patients responded. On the other hand, studies using MS-E to select patients showed a significantly better response rate at the BASCET trial, Keynote 28. For example, we see here the same drug in the Keynote 28 study using PD-L1 for selected patients. 13% of patients with endometrial cancer showed a response to pembrolizumab compared to 57% of response rates when MS-E was used for selected patients in Keynote 158. In the case of Garnett, in the court of patients with incompatibility repair deficiencies, the response rate was around 42%. In this significant increase in response for the use of MS-E was also observed in the Phase II study of anti-PD-L1, durvalumab and avelumab. Here in this table we can see data compiled on immunotherapy in patients with endometrial cancer selected based on the MMR repair incompatibility deficiency, varying from 26% to 57%. In endometrial cancer, there is a significant overlap between high-mutational tumor load, MS-E, and 25% of patients, but not between these two subgroups and PD-L1+. Focusing on sensitivity and specificity, immunohistochemistry has a sensitivity of around 92% and a specificity of 99%. According to some evidence presented at ASCO last year and at SCGO this year, there are differences in the response rate according to the mechanism behind protein loss in immunohistochemistry. Patients with Lynch syndrome had a better response rate among them. In retrospect, according to molecular analysis in patients treated in the PORTEC-3 study, chemotherapy in the adjuvant scenario is less effective in patients with incompatibility repair deficiencies. On the other hand, there was a significant impact on the free survival of patients with TP53 mutation. Speaking of the serous type, it covers about 10% of all these patients with endometrial cancer, and according to the TCGA, it has the worst prognosis. 25% of them have HER2 superexpression. We are seeing here the free survival curves of the initial study of Dr. Fader with the combination of trastuzumab, chemotherapy, CARBO and Paclitaxel, where there was a clear benefit of free survival of progression, which was predominantly found in the initial phases of stage 3 and 4 tumors compared to the residual population. This benefit of free survival and progression was found predominantly in patients in the initial stages and was demonstrated again in the updated analysis. More importantly, there is a clear benefit in global survival with the addition of trastuzumab to chemotherapy in patients with positive HER2. Again, this benefit was clearer in tumors in advanced stages compared to patients with residual disease. Previous tests of hormone agents in endometrium cancer show modest activity based on the free-of-progress survival response. These data provide us with a basis for evaluating future combined therapies, such as hormonal therapy with anti-PIK3K and hormone therapy recycling inhibitors, study of letrozole value combined with ab-macyclib. and the initial context. Initial and advanced studies are including patients based on molecular characteristics. Here's the first one, GOG3064, including patients based on impairment repair deficiency, studying Pembrolizumab, and also in combination with chemotherapy, or chemotherapy alone, and in initial settings, studied here in PORTEC4 and in RAINBOW as well. I would like to thank you, I want to thank you all for being here, and thank you for your kind attention. It will be my pleasure to answer your questions. Thank you very much. Dr. Fernando, thank you. Thank you very much, Dr. Angélica. This was a fantastic presentation, very rich. It was very good to address these things that we, surgeons, think of as scientists, or as basic sciences, about clinical practices and the introduction of these profiles, when it was something slow, it seems that now, at least here, it's something much better, and this will be the present and the future of our topic. In this way, let's start our round of questions and answers with our survey here. Let's answer our survey from Dr. Angélica Nakueira Rodrigues. The biomarkers that impact current endometrial cancer therapy, what is the incorrect option, please? Incorrect option for endometrial cancer treatment. Okay, don't be shy. So, most of the attendees said that PD-L1 is an excellent biomarker to select patients for immunotherapy. Let's see. Good morning, everyone. It's a great honor to be here. Thank you, Fernando. He's here with me, by the way. We're together here. Thank you very much for this opportunity you're giving me. It was a fantastic lecture. Yes, it was a fantastic lecture. But for us surgeons, we see with great interest what is happening in science and how this translates into clinical practice. In this way, the implementation of both terminations of these molecular profiles in our low-income countries, this has been slow. For example, in Chile, I think the same thing should happen in other Latin American countries. Because this termination is expensive. But MMH, proteins, it's very easy to treat. How have you implemented this in your practice? What would be your recommendation? The doctor says this is a very important point in patients who are in low-income countries. But the positive aspect here, Fernando, is that most of the markers can be checked with various eyes. And all patients who have endometrial cancer can do these stability studies. And the positive side, the good aspect of all this, the good side of all this, is that this is the way to select patients. We don't need PMB for most patients. The doctor has already shown us that 5% to 6% of stable patients, they can have PBMB. But we do this for the majority of patients. So, the sensitivity for this stability, using the immune system, is around 95%. So, this is very positive. At least in Brazil, it is already available. Or in most public network hospitals. But I think this is a positive point. And the other issue is that it's expensive. It's worth around $300 here in Brazil. But the price will decrease, I'm sure. In this way, I believe we will have access soon. And we can fight to have this access. Because this will change. This will change for a very well-defined prognosis. So, we consider this very important for our patients. We have two more questions that are similar. One from Fernando, the other from Audrey. When we ask for the pathologies, I don't ask for the pathologies. Because it's not a conventional morphological biopsy. It's a common morphological biopsy. In this morphological biopsy, biomarkers, the option to use this or classification will depend on the availability of the resources, says the doctor. And the multidisciplinary system. So, if it's available, I think we should do it to all patients with poly at the beginning. Because even in these cases of stage 1 or 3 cancer, according to the guidelines, these patients must go through tests to be able to measure the stability in which the proteins are inserted. So, this is the guide, the promise guide that exists in the IGSN, which can help define the treatment. At the time of making the diagnosis, it's very important that only 5% of patients with endometrial cancer, the life expectancy is 70% in these patients who have an endometrial cancer. So, it's very important to do this test focusing on cancer prevention. And what happens... I'm sorry, I'm having audio problems, okay? 30% with endometrial cancer, but also in patients with sentinel. Now that we have these new therapies, we can increase the progression. And also in this stage of stage 2, evidence showed that we had a gain in the survival results. But here, especially in these low-income countries, this becomes a problem for these low-income countries, these positive data for stage 3 patients. In this way, for all serous patients, I would say that this would be the treatment. Here in Venezuela, I lost my name, I apologize. He greets us and says it's a fascinating talk. And he asks if it's possible that in the future these molecular studies of biopsy before surgery would be done. Yeah, I hope so. Especially for us, the surgeons. Dr. Angelica says yes, I hope so. There are so many tests that are being done referring to medical oncology, trying to scale the treatment. If you have, for example, the patient's information, if it's a poly mutated patient, then it's better for this surgery to be indicated. But these tests are doing the classification of those favorable, intermediate, and unfavorable patients. So, the patients will go to conventional therapy if it's stage 1, and that way it's scaled, if it's not immunotherapy. I think that's it. The tests help with that, with this issue of scaling. And here's a question from some other markers. Yeah, I lost it. I think it's IL-1K. For example, if the patient expresses more than 10% of IL-1K, the patient is at high and intermediate risk. So, in this way, we're including patients in the certified afforded suite. And for patients who are IL-1K, for example, patients who are IL-1K are classified as unfavorable compared to conventional therapy. So, data is coming. I don't have it yet. But we're going to have prospective data, again, but when it's decided, it looks like it's going to be balanced by your markers. I'm sorry, I'm having audio issues. Okay, we have a couple of more questions, but unfortunately we need to continue with our schedule. Thank you very much, Angélica. If you could answer all the questions internally. I see a lot of pathologists who are very interested in your work. So, please, let's answer all these questions. Thank you very much, Dr. Nogueira-Rodriguez. I will answer all the questions in the chat. Our next presentation will be by Dr. Simons, Controversies in Radiation for Endometrial Cancer. Hi, I'm a clinical oncologist at the University Hospital Plymouth Trust in the United Kingdom and affiliated with Stellenbosch University in South Africa. I have no conflict of interest. And today we're going to talk about endometrial carcinoma and the controversies in radiotherapy. So, we're focusing on endometrial carcinoma, endometrial carcinoma, light and serous cells. We're not going to discuss carcinoid sarcomas because they're not very well evidenced in the literature. And we're not going to discuss sarcomas because they're a separate entity. So, we're going to focus today just on the role of adjuvant radiotherapy for these patients. So, there are a number of prognostic factors known for endometrial cancer. These include the stage of the tumor, degree, subtype, histological, depth of mitral invasion, more or less than 50%, evidence of vascular lymph invasion, if it's minimal or substantial, and the age of the patient, usually above 60 years. So, how do we take the current evidence and the knowledge of these risk factors and apply it to our daily intake? Keeping in mind that the addition of radiotherapy does not affect global survival in the initial stage of the disease. Some definitions for those who are not oncologists. When we're talking about external radiotherapy, or EBRT, we can refer to 3D, radiotherapy for the pelvic and or for the pelvic and paraortic lymph nodes as appropriate, depending on the pathology. And these patients will receive five weeks of daily fractionation. On the other hand, we have vaginal brachytherapy, or VBT, and cylindrical brachytherapy, usually administered in three or four stages, administered as an autonomous treatment, and chemotherapy, and carboplatin, Paclitaxel. So, what is this? We'll start with PORTIC I, which was a study of radiotherapy analyzing the outcome of pelvic radiotherapy versus no treatment for the initial endometrial carcinoma. They included stage 1 patients with a degree 2 or 3, invasion of less than 50%, or degree 1 and 2, with an invasion of more than 50%. Patients receiving external or randomized radiotherapy for no additional treatment. The last 15-year follow-up was published in 2011. The main difference in the study was that the local incisive rates were higher in those who did not receive radiotherapy. It was particularly observed that patients had a chance of almost 75% higher of the local incisive rate in the vagina, but there was no difference in the survival rate. As we can see in the graph, there is no difference in the survival rate, free of failure. What they found in the multivariate analysis was that patients over 60 and degree 3 were indicators of a worse prognosis. But the final conclusion of the study is that external defection radiotherapy had no effect on global survival in this group of low risk intermediates. Then came PORTEC-2, which was published again more than 12 years ago, analyzing vaginal brachytherapy versus external defection radiotherapy in this same group of patients, or similar group. They included patients with less than 50% of myometrial invasion, degree 3, more than 50% of invasion of degree 1 or 2 and degree 2A, which we don't have anymore. But as you can see in all the graphs, local incisive rate, global survival, free of disease survival, there was no difference between the two groups. Here, showing no difference in global survival. Therefore, a very important result was the reduction of gastrointestinal toxicity for patients who received only complete brachytherapy, which is obviously beneficial to consider whether pelvic radiotherapy is necessary in this group. The final conclusion in PORTEC-1 and PORTEC-2 is that isolated vaginal brachytherapy is the choice treatment for these high-risk patients. Then followed PORTEC-3, looking at the other end of the spectrum of high-risk patients with multiple risk factors in groups of degree 1 and 2 and all patients with disease in degree 3. Here they are looking at adjuvant chemotherapy versus just radiotherapy. So the groups that were included were 1A, serous, light cell, 1B, degree 3, or all lymphocytic patients in stage 2 and any patient in stage 3. So the remedy was chemotherapy, five weeks of radiotherapy with 50 mg cisplatin per square meter in week 1 and 4, followed by adjuvant chemotherapy and carbotaxel, as discussed, for four cycles versus just radiotherapy alone. So the outcomes for the patients in stage 1 and 2 were not different in global survival or in the results of failure-free survival, but a notable difference in global survival of more than 10% in patients in stage 3 and more than 10% in failure-free survival for these patients. We can see here in the graph a risk rate of 0.63 for patients receiving chemotherapy and radiotherapy together versus radiotherapy isolated in stage 3. Pelvic radiotherapy is sufficient for patients at high risk in stage 1 and 2 based on this study. Chemotherapy and radiotherapy are probably the best treatment for those at high risk with disease in stage 3, which is an unknown benefit and for patients with a high risk. They showed an improved global survival, but it was a small group of 100 patients and possibly very small to differentiate by stage. What we know at the end of port 3 is that patients in stage 3 should probably have chemotherapy, but as we schedule, we are sure that carbotaxel is the right chemotherapy, chemotherapy is necessary. These two cisplatin cycles are necessary along with radiotherapy, which we can only give chemotherapy and adjuvant chemotherapy. Unfortunately, all of this remains unknown. But wait, there is much more behind it. Equivalent studies carried out in the United States such as GOG 2419, which was a phase 3 study that analyzed patients with endometrial carcinoma at high and high-risk stage 1. They gave pelvic radiotherapy versus vaginal brachytherapy and a little chemotherapy. But there was no difference in global survival between chemotherapy and brachytherapy versus isolated radiotherapy. So pelvic radiotherapy was equivalent to chemotherapy. Here they gave three cycles of carbotaxel equivalent to global survival, but there was a reduced local failure rate in patients who did not receive any pelvic radiotherapy. The conclusion of the study and the authors is that pelvic radiotherapy is the way to go, especially considering toxicity. Based on PORTEC-3, if you have a serous carcinoma, you could consider the addition of chemotherapy along with pelvic radiotherapy. But then came GOG 258, which was the North American equivalent of PORTEC-3, published in the same year. Here they looked at adjuvant chemotherapy plus radiotherapy versus chemotherapy alone in locally advanced endometrial carcinomas. It's different from PORTEC-3 because it has no brachytherapy alone. Here they did not find a difference in the free survival of residue between chemotherapy and chemotherapy alone, but a greater incidence of vaginal residue and residual in the dow, both in the skin and in the paraortic regions for patients who received chemotherapy alone. So, for a locally advanced endometrial carcinoma, if you follow the studies of GOG and the conclusions of the authors, it is that chemotherapy is enough. But my concern here is that chemotherapy plus radiotherapy show improvements in the local failure rates. And as clinical oncologists, we analyze the local survival and results. Very well, what would I do? The only group of patients that I would offer adjuvant chemotherapy as external failure radiotherapy are the patients of stage 3A and B, which are of a higher degree, anyone involved in the dow and serous stage 1B and 2 carcinomas. There is no doubt that all patients with endometrial carcinoma should receive some form of radiotherapy, be it vaginal therapy or external failure radiotherapy, if they have an endometrial carcinoma above a low degree, 1A. The future developments for the recruitment of radiotherapy studies at the moment is PORTEC 4A, looking at patients in stage 1 with some risk factors, including high-degree lymph vascular infarction. And now we are becoming medical oncologists because we are trying to integrate the molecular profile of the tumor into the decision-making tree in relation to radiotherapy. And this study divides the patients between those who have a POLL-I mutation in a favorable group, those who are deficient in MMR, if they are, is included in an intermediate group. It can also be included in a favorable group, if it is CTNNB1 wild-type, if it is not deficient in MR. And then there is the high-risk group, those who have substantial evidence of lymph vascular infarction in the tumor of a TP53 mutation or expression of L1CAM over 10%. This is the unfavorable group. So these patients will be aliased in the standard arm to receive vaginal brachytherapy. If it is included in the favorable group, only, and observation, in the intermediate group, vaginal brachytherapy, and then in the unfavorable group, they will be estimated in less than 5% of the cohort and will receive external fascia radiotherapy. So my final considerations are that you need to consider your resources. For those who work in a region without access to radiotherapy, they will have to observe the patients in the initial postoperative stage. And for those who are high-risk, intermediate, they can consider three cycles of carboplatin, paclitaxel, and for patients who are very high-risk, six cycles of carboplatin, paclitaxel. And for those who have access to surgery and some access to radiotherapy with possible long waiting lists for radiotherapy, observe a low-risk initial stage of vaginal brachytherapy, according to Portec2 studies, for patients in stage 1, intermediate, and also high-risk, intermediate, they can give external fascia for patients in high-risk initial stage, stage 2, according to Portec3, or GOG249, if there is not a very long waiting list. Then they can give chemotherapy, six cycles of vaginal brachytherapy, if they have for high-risk patients, stage 3 and 4A, according to GOG258, if there is a very long waiting list for radiotherapy, they have to use their available resources. If you have surgery and access to all the modalities of radiotherapy, without a waiting list, my suggestion to follow is the evidence, choose your team. Here, my sense of responsibility is that I follow the European diaspora and for locally advanced and high-risk patients, I would offer chemotherapy and radiotherapy together. In my clinical practice, I would offer chemotherapy and radiotherapy alone. Thank you very much for your attention and I look forward to your questions. Thank you very much. Thank you very much, Dr. Simmons. Great presentation. Very well. What you showed was actually radiotherapy through history in endometrium cancer and also articulation with molecular profiling in endometrium cancer. Let's start with our questions, but first we will do a survey. In relation to treatment for patients with endometrium cancer, what is true? Choose a summary answer. Okay, don't get lazy. Almost there. A little bit more, a little bit more time. Okay, let's see. All right. That's... It says here, PORTEC-2 study concluded. And again, PORTEC-2 studies, that's the most answered study. So, the one that got the most answers. All good, I wish I was there. How are you, Dr. Simmons? Very good, I wish I was there with you. It's a little bit warmer here than in England. I'm traveling to England next week. Okay, so molecules again, see how the molecular profiling is integrated in this adjuvant treatment. We talked about this during the presentation with Dr. Nogueira, with Dr. Nogueira's presentation. We have a question about PORTEC-4A. Do you believe that before the results, there will no longer be validity in time because the RAINBOW study already offers adjuvant chemotherapy for all those patients with these mutations? That would be the problem with these studies. It takes a long time to design the studies. It takes a long time to convince people to participate and also to get the results. The science behind it is already valid. So I don't think there's any doubt that many people are using this information in their daily clinical practices. P53 is unlikely to provide this therapy. Although I don't like to criticize my colleagues, I think it's interesting that PORTEC-4A doesn't offer chemotherapy for high-risk patients because of the way we do it. There are always some differences between European studies, Latin America, and we don't have so much work on chemotherapy. Compared to the United States, possibly they could also use a little more radiotherapy, but I think we should see these high-risk characteristics and thus make a decision about what to offer to the patient before the results. So in the daily clinical practice, we use MMD or P53 to decide on the radiotherapy treatments. Radiotherapy is because we have the two available modalities, MMR and the PORTEC study, which says that we shouldn't give those to the patients. We should leave those to the stage 3 patients because that's what we do in the daily practice. And patients with P53, we have other different things that could be, because they are considered high-risk. So, in general, coming from a European and South African point of view, we use a lot of radiotherapy. Much, much more. I understand perfectly. We also use a lot of radiotherapy. We have availability of radiotherapy, but it's not a matter for low- and middle-income countries. Your last slide was very interesting because you have to use everything you have within that availability within your countries. So, I really would argue heavily for people to consider a type of radiotherapy for high-risk patients because the local residue is a very unpleasant outcome. And if you don't do a follow-up, as we do in Africa and certainly in some Latin American countries, it's too late when this patient has a residue because that residue is terrible, really. Very well. I think those were the questions we had. Let's continue with our next presentation. Thank you very much, Dr. Simons. It was very interesting, your presentation. Very well. Let's continue with our last presentation, Dr. Bill Wilmy from Argentina, who will present technical aspects in endometrial cancer surgery. Welcome, Dr. Juliana. Hello, everyone. My name is Juliana de Wilmy. I am an oncologist and gynecologist. Hello, everyone. I am an oncologist at the Hospital of Buenos Aires. I would like to thank you for being connected today and participating in this webinar series on topics selected and interactive in oncological gynecology and thank IGFES for such a cordial invitation and organizations of this interactive module on topics of interest in oncological gynecology. I have no conflict of interest for this lecture. This lecture will address technical and surgical topics of endometrial cancer. I divided it into two parts. In the beginning, we will talk about theoretical concepts related to the discussion we can propose regarding the approach and some small areas of discussion. Some are clarified, others are not. The second part of the lecture will be oriented to more practical concepts in relation to the use of the sentinel ganglion, in relation to specific surgical techniques for a final recommendation on how we should organize ourselves to perform the complete staging of endometrial cancer, how to organize ourselves based on practice, experience and theory at the time of staging endometrial cancer. Well, I want to talk about the approach and whether it is safe or not to use the minimally invasive path for the treatment of endometrial cancer. The most modern study with which we count, and I think it is one of the two prospective studies we have, is LAST TRIAL, in which it was seen prospectively the use of the minimally invasive path versus the open path and showed that when comparing patients who were operated on the open path versus the minimally invasive path, the results in oncological terms were similar. And these results from LAST TRIAL were also demonstrated in a previous study, well known to everyone, which is CIOCHIP-GOD-LAB-2. There is something you can tell me, which is that in these studies, the vast majority of patients correspond to low-degree histologies and initial stages. In this subsequent study, where patients were grouped with CIOCHIP-GOD-LAB-2, which had unfavorable histologies and degree 3, it was also possible to show that survival was the same by comparing the approaches. That's why I think the most practical recommendation is that we all strive to evolve, to have the best training, to make endometrial carcinoma patients have a stage and be treated by a minimally invasive path, always, obviously, having the repairs in relation to oncological surgery in general. Following this point, I would like to propose the use of the manipulator, a point of discussion on the use of the uterine manipulator in the treatment of endometrial cancer. When we do minimally invasive surgery, whether acrobatic or laparoscopic, we rely a lot on uterine manipulation through the vagina. And this is an area that we thought was a bit closed. There is a 2017 article, retrospective, in which it compared patients who had used it versus patients who had not used the manipulator. We were calm because it showed that both the residue rate and relapse did not show differences in the group of patients. A little while ago, a Spanish study was published, where also, retrospectively, when comparing patients who used it and patients who did not use the manipulator, we can see a higher rate of relapse and mortality in patients where the manipulator was used. I think that neither of these studies can be 100% safe, because there are biases, right? There are studies where we do not know why they used it, why they did not use it, what type of tumor, in what conditions the uterine manipulator was used. But I think that, yes, we must be careful, especially in those patients with high-risk carcinoma, large tumors, where the manipulator can generate a certain dissemination. And also the perforation of the uterus, right, people? I think that the perforation can play a role in tumor dissemination. So, at the time of placing the manipulator, or at the time of manipulating the uterus during surgery, we must be careful in general oncological surgery to try to offer the patient the best possible results. The last point I want to propose as an area of discussion is the use of peritoneal cytology within what is endometrial cancer surgery. What we know does not constitute a stagnation as such has an uncertain role, but yes, in patients who have neoplasmic cells in the peritoneal cavity, the prognosis is worse. I think that in this scenario of uncertainty, of great uncertainty, it is said that peritoneal surgery is no longer being used, which can help in the patient's global assessment, especially in patients who are at high risk. I think that the practical recommendation for this is not to stop doing this, not to forget, as much as it does not have an important role nowadays, it can help when we need some other data from the patient. So, let's move on to the second part of my presentation with more practical concepts in relation to the use of the sentinel ganglion and the punctual surgical technique. The use of sentinel ganglion in the stagnation process has practically become a standard today, as a less invasive practice, which reduces subsequent complications and which does not act to the detriment of metastasis detection, since we are seeing that we will even detect more metastasis, and this can be explained due to the appearance of low-volume metastasis, micrometastasis and ITC. It is important to have the technique clear, to polish the technique, so as to be successful in detecting it. Let's quickly see some concepts based on surgical technique. The first step within the global surgical strategy is to evaluate the abdomen, obviously, to be able to rule out advanced carcinoma disease and, after that, make a good evaluation of the skin, especially to be able to rule out adherence, unblocking of the pelvis, which causes a delay in the dissection of the corant and in the search for the sentinel ganglion. And this is because the vast majority of corants, the green endocinema, it takes a certain time. The second step, and probably the key to success, is the dissection of the corant. For endometrial cancer, it has already been studied and this injection must be at 3 and 9 o'clock, bilateral. The more lateral we make the corant, it gets closer to the pelvis and, above all, dedicated. Use a suitable needle, okay? I recommend this 21G needle. It must be a needle that has enough width and hardness, enough firmness In addition to a correct dissection, it is important to have a good timing, that is, to do the dissection and, as we do it, see how the corant drains backwards. Or see by transperitoneal how the corant drains towards the pelvis and the other and already having at the transperitoneal level an idea, a location and also at this point. And this timing goes in relation to the times that the corant has to reach the ganglion and soon spread, stain the field and have a correct location of the sentinel ganglion. Our surgical aspect, with a technical basis, is that when we are looking for the sentinel, we must be very delicate when it comes to dissection, especially the dissection of the lymph nodes, which go from the uterus to the lateral part, in the pelvis. If at the beginning we do a dissection of all these canals, they will be cut and the corant will not reach the sentinel ganglion. On the other hand, I think it is also important that when we do the sentinel ganglion, identify the vascular, nervous, anatomical structures and when we do a lymphadenectomy, have at least identified, without cutting the canals so as not to affect the lymphatic drainage. It can cause a lymphedema, therefore, avoid the dissection of the large pelvic structures. Finally, and also as part of an adequate technique related to the whole process of the sentinel ganglion, the extraction of the sentinel ganglion, is that you extract the tumors through the technique, through a careful process, inside a bag. It can be inside the finger of a glove. Soon after the identification and extraction of the sentinel ganglion, the surgery continues, performing a hysterectomy for endometrial carcinoma, which corresponds to a PIVER 1 hysterectomy or a Class A hysterectomy, where the secession of the uterine vessels is at the level of the arrival of the uterus in the stomach. Unlike radical hysterectomies, which are used for carcinoma of the uterine colon, where the dissection of the hyper-uterine film is at the level of the ureter for PIVER 2 or at its origin, which is PIVER 3. Radical hysterectomies for endometrial carcinoma are subject to few cases, and the discussion is whether when the endometrial carcinoma enters the colon we should do a radical hysterectomy is a longer discussion about this. There are studies that show that there would be no difference between doing a radical hysterectomy or a PIVER 1 hysterectomy. Be very careful when the hysterectomy is done, the dissection, the coloptomy to be in an adequate way and also the extraction of the piece by the vagina, that it be in a careful way, with the intention of not spreading the content in the vagina or the content that may come out of the uterus to the abdominal cavity. The following is the role of freezing, biopsy, intraoperative, when we can complete the hysterectomy. This happens because usually prior to the use of the ganglion, in many centers we base it on intraoperative freezing as a definition of risk at this time, in high or low risk patients, to complete or not a systemic lymphadenectomy. I think that nowadays, the era of the ganglion, the intraoperative biopsy has decreased a lot, it is no longer being used much and we can use it or it can give us a panorama in the sense that we have not detected a ganglion, and in this way define risk factors for intraoperative biopsy to complete or not the lymphadenectomy on the side where we do not find the ganglion. In this way, intraoperative biopsy, what helps us is to reduce the amount of unnecessary lymphadenectomies. Finally, and to finish, we make a brief summary of everything and a recommendation. The carcinoma surgery of endometrium starts with a careful inspection of the cavity, especially of the pelvis. Pay attention to those patients who have a high degree of unfavorable histology. Remember that this can give us a greater global assessment of this patient. We continue the surgery by injecting the dye to perform the sentinel ganglion. Remember to do a cervical injection very carefully, sub-epithelial, via superficial. A deep injection, if you want, can be done, but usually the success of the detection of the sentinel ganglion is in the superficial injection, very meticulous. And after this injection, we can put the manipulator. Remember, ladies and gentlemen, that the uterine manipulator also for endometrial cancer, it can cause some effect, especially in large tumors, high-risk tumors. In this way, make a careful posture, as well as careful manipulation during the surgery. And make, dedicate your efforts with the intention of advancing, getting to know and having, as quickly as possible, the curve of experience for the sentinel ganglion technique. It is not necessary to have cyanide green, better cameras, we can do it with blue, isosulfone, with patent blue. The important thing is to be able to do this, to be able to train, because it is a technique that is less invasive, it does not mean that it is easy, but it requires a training curve greater than a lymphadenectomy. Complete the surgery with sterectomy. This is a PIVER 1 ocular CA sterectomy. Be careful, obviously, in the removal of the uterus, in the copotomy, in the normal separations of an oncological surgery, in this way, to avoid dissemination. Use the biopsy for freezing as a criterion to define risk factors intraoperative. When you have doubts about doing the lymphadenectomy or not, but above all, when there is the sentinel ganglion technique, use the intraoperative freezing. When none of the two ganglions have been found, complete the lymphadenectomy according to the high or low risk criteria that you use in your hospital network. I want to thank you very much for listening to me. I hope this talk has been useful for everyone and I am here at your disposal to answer the questions you may have. Thank you very much. Thank you very much, Mr. Julian. Excellent presentation. How important it is to acknowledge all these tips to stand up, to standardize the procedure. So, let's start with the questions and answers. This is the last poll for the people who are participating, so you know. Some technical aspects are important in surgery. Please choose the wrong answer. All of you, 271 participants right now, you can answer. Don't be shy, this is the last one. Please participate. Okay, let's see the answers. Most of people said that once sentinel lymph no... What do you think about this? What do you think about this? How can this technique be introduced in our day to day for patients with endometrial cancer, doctor? Good morning, Fernando. Thank you very much for the presentations. Thank you for the invitation to be with you here today. I hope I was at the level of the other speakers. Fantastic presentations, right? Of course, it's like that. Well, he keeps saying that regarding the punctual question, recently, and even today, we see that they ask us to talk about a standard, how to transform into a standard. I think that the assessment, to say that a technique is standard, will depend even on the place where we are working, it depends on the region, it depends on the hospital. In other words, we think that this should be the standard. We saw in Mariane's presentation and practical evidence, there are studies that show that it is not only a less invasive method, but also a method that offers better diagnosis for what we are looking for, for the treatment of cancer. We have a better assessment, we have a better view of the patient regarding the prognosis and it helps us a lot to see the adjuvance. This goes together, right? Not only with the technique that I am showing. The technique of punctually finding the most representative ganglion, but if the study of this ganglion, the idea is that it accompanies the whole process that we diagnose more and more. And as we are seeing, it will increase the rate of lymphatic metastasis that we are diagnosing, compared to what we used to do before, micrometastasis and tissue. But the idea is to promote a little use and the development of this technique, which, although it seems like a less invasive technique, requires a long learning, a curve, a training, so that this technique can be done well. Without a doubt, Juliane and Fernando, we comment on this because it is a subject that we love very much and I know that you have been, you are the pioneer of this. Well, regarding this, we have a question from Ignacio Chaves, who says, who are the people who adopted the ganglion in the endometrium? Did everyone validate their local false negative with ganglion and lymphadenectomy at the same time? I think this question has to do with the curve. In my particular case, the first, I did the ganglion in blue. Nowadays, I work with green endocyanin, but there are people who do not have access to it, to green endocyanin. What would you say to people who want to start using this technique, to be able to validate this technique in their hospital centers? He replies that in order to do only the ganglion, it is essential to do the own validation, the evaluation of each one. This is achieved through cases where we do, for example, lymphadenectomy, compare the ganglion with the others. They are false negatives, that is, that the ganglion is negative and the lymphadenectomy is positive. This, on the one hand, and on the other hand, obviously, to be in continuous contact and ask about the pathological level, the inclusion. The sentinel ganglion, unlike the lymphadenectomy, must have a much more extensive anatomical and pathological study. Do another test and another negative test. In this way, go to immunochemicals with cetokeratin to detect, for example. So, pathologists must have a pattern and know that the sentinel protocol is not very widespread. Otherwise, it will be useless. Again, it is in cooperation with our pathologists, anatopathologists, to say, this particular ganglion, I want it to be studied this way. Otherwise, the surgical effort I am making to change my surgical practice for the sentinel ganglion, to be able to offer the benefits of this technique, it will simply be useless. If we don't do another test, it will be useless. There is also a question that you would use, only the sentinel ganglion or the sentinel ganglion technique in cases of patients with high-risk tumors such as carcinoma of light cells. That is, do you feel comfortable using this technique in this type of patient, doctor? He answers that nowadays, for high-risk patients, in prospective studies such as TRIAL, which is a retrospective study for high-risk patients, when we are performing the technique, when we validate this technique, and its detection rate is good, in this case, we can truly rely on the detection of sentinel ganglions. There was a question about what we did before, right? Of course we don't feel comfortable when we don't find it. And then we must make the decision to do the lymphadenectomy, because if it is ventilated for a high-risk patient, it cannot be a hemipelvis or both, without checking the ganglion state. Is this aspect important? But yes, when we have already made our learning curve in the place where we work, the technique is installed. And with this technique, we can pass it on to patients, including high-risk ones, too. How important is the standardization of this technique? That is, that our technique is always the same. Can we then offer favorable results, validable results, and results that preserve the oncological benefit of endometrial cancer surgery? Many of the questions that came up, both in the Q&A session and in the chat, refer to this, the depth of injection, how many mLs, this is something that is very standard, right? In my case, for example, I have already talked to many colleagues, what injects the green endocyanin is always the same assistant, it is always at the same speed, while the other is looking from above, that is, everything has a perfect timing. A good question is, how much to re-inject, doctor? Well, regarding this, I think this is part of the global technique and the success between a good detection rate. My recommendation for re-injection is that you do, for example, we are injecting the patient, we are looking directly through the lighting, when we see that the corant is not parallel to the uterus collar and there is no canal that we can approach, it is time to be calm and follow the re-injection. I think that many times situations happen where we find the ganglion on both sides. And I want to say something, Fernando, based on what I've been telling you about the technique, I think the technique itself has been standardized. There are things that I showed in my video that talk about specialist recommendations. Today we find articles based on standardized techniques for sentinel ganglions, things that should be done, things that we shouldn't even do. And I think this difference between the first works where we saw that sentinel ganglions were detected less than half the time, nowadays it is standardized with this. And we already have greater learning, we can see the steps for the detection rate can be very high, following the steps. And we have the last questions from Dr. Fernando. I know there is some variation in the technique when we use azumite and methylene versus green endocyanin. This is very easy to answer. Green endocyanin made it even easier. It has a high cost, it already has second-generation cameras and they are integrated into robotics, but if you don't have green endocyanin, you can use blue, as long as, as we previously mentioned, you make a curve and see your possible false negatives. Well, based on that, what we showed a little while ago, referring to the timing, the injection place, even the amount of dye to be used, all this is similar, ok? Obviously, green endocyanin made it easier to visualize the fact of continuing a subsequent surgery that doesn't have any blue spot. I think, in that sense, it improves the issue. We must say in the Latin American webinar that, many times, the transition from one technology to another requires a greater effort when it comes to technology and getting the dye that helps us. Well, let's close our session with this, Dr. Fernando. We have a lot of questions in the chat, but we are already on time. It was fantastic, this event. In this way, I want to thank all of you, Dr. Julián, excellent presentation. Well, and we're done for today. I want to thank the hosts of today, who made this meeting possible, and I want to thank our speakers for dedicating their time and for all their contributions. And I want to thank all the participants around the world who are here today. We have people from all over the world, and thank you very much for choosing me as moderator of this webinar. Today's recording will be available on the portal next week, so remember to join us next Saturday for the third session on ovarian cancer. Thank you very much to all of you. Have a great day, everyone.

endometrial cancer

treatment options

metastatic

recurrent cases

inhibitors

hormonal therapy

anti-HER2 therapies

immunotherapy

microsatellite instability

biomarkers

research

investment

systemic treatment advancements

molecular knowledge

surgical approaches