So, hello, everyone. We will start in one minute. So, hello, everyone. Welcome to the interactive... Welcome to the Oncology Webinar. Today, we will talk about Oncology, Oncological Gynecology. Today, our program will focus on Uterine Throat Cancer. I am Reitan Ribeiro, and I will be your moderator for today. Today's webinar will be recorded in English, Portuguese and Spanish. We have a simultaneous interpretation service, and these are the instructions that you will find in the chat about how to connect and how to listen to the other languages. Here we can see the English and Spanish instructions. We also have the interpretation button here, and you can choose, in this way, the language of your choice. You can put the original audio on mute if you want, too. If you have questions about how to access the simultaneous interpretation, contact IGCS. This webinar will be recorded, will be open and available on the IGCS portal. You can ask questions at the bottom, where it says Q&A, and in these sessions we will have questions at the end of each session, and we will try to answer as many questions as possible. In today's webinar, the topic will be cervical cancer. I would like to introduce today's speakers, Pedro Ramírez from the United States, Aldo López Blanco from Peru, Mauricio Lema from Colombia, Anuja Gingran from the United States, and Renato Moretti Marques from Brazil. To kick off today's presentation, we will share with you Dr. Pedro Ramírez's presentation. On surgical treatment and the impact of the study called LAC, L-A-C-C. Thank you very much to IGCS for the invitation to present this topic. The topic of this discussion will be the surgical treatment of patients with cervical cancer and the impact of the LAC study. During this presentation, I will address the final results of the LAC study, which were presented at the meeting in Phoenix in 2022, which shows the summary of all patients monitored for four and a half years. We will talk about the literature published in 2019, when the LAC study was initially published, and some patterns of practice in the United States, and I will talk about some issues that have not yet been resolved, and that still remain, particularly, talking about the maneuver of vaginal protection, and also the issue of patients with less than two centimeters of tumors. And finally, I will talk about the impact of the LAC study on national and international guidelines. As you well know, the LAC study was a randomized study that evaluated minimally invasive surgery versus open surgery. The recurrence rate was much higher, and the overall survival rate was worse in patients who had minimally invasive surgery. Subsequently, there was another study published in the same edition, in the New England Journal, in 2018, by Alex Melamed and his group, where they evaluated a national cancer database, comparing open surgery versus minimally invasive surgery, and it showed that minimally invasive surgery was also associated with worse survival outcomes for these patients. At the recent meeting of the Oncological Gynecological Society, I had the opportunity to present the final analysis of the LAC study, and in this presentation I talked about the outcomes of free survival of diseases and overall survival in patients who were subjected to open surgery versus minimally invasive surgery at the age of 4 and a half, that is, when 100% of eligible patients were followed for 4 and a half years. In addition, we did an exploratory analysis, and again, it was an exploratory analysis, and none of these points were in the initial design of the study, but since this was of interest to the community of oncological gynecologists, we decided to evaluate the impact of residual disease on the hysterectomy specimen and the approach to open surgery, minimally invasive surgery, and there was a gap in the impact on these patients, the rate of patients with lower tumors at 2 centimeters versus those with larger tumors at 2 centimeters or equal to 2 centimeters. As we know, in the study we recruited 631 patients, and as I mentioned, this is the stratification of all the patients who reached those 4 and a half years, which means 83% of all the patients who were in this study who reached those 4 and a half years of study. As you can see, we had 100% complete data for all eligible patients, for both primary outcomes and free survival of diseases and overall survival. In our final analysis, we showed, as in the initial publication, that both in the analysis for the intent to treat and in the protocol analysis, minimally invasive surgery was associated with worse outcomes, and therefore, radical hysterectomy favors the open approach to these patients by evaluating free survival of diseases. As we can see here, in terms of residual events, these were four times higher in patients subjected to minimally invasive surgery compared to open surgery. In addition, free survival of progressions was also worse in patients subjected to minimally invasive surgery compared to open surgery. Specific survival of diseases was also almost three times worse in patients subjected to minimally invasive surgery compared to open surgery. And in the local and regional recidivism, which is also interesting. The interesting thing is that the number of patients with minimally invasive surgery was five times higher compared to patients who had laparoscopy or robotic surgery. And finally, when completing the study there, after 4 and a half years, when 100% of the patients were followed, we showed that minimally invasive surgery had three times worse overall survival, that is, in other words, three times more death rates from cervical cancer when compared to open surgery. And obviously, this was an important finding, because it solidified and rectified the initial publication in the New England Journal of 2018. As I mentioned, we did an explanatory analysis, and first we analyzed if the impact of residual disease on a kind of hysterectomy had any influence on the outbreaks. In other words, patients who don't have residual disease go through radical hysterectomy. It's important to note that when looking at this particular component, there were few patients who didn't have residual disease. So 60 patients in open surgery and 60 in minimally invasive surgery. And as you can see here, there were no residual events in the patients who did open surgery. And there were only two residual events in patients who did minimally invasive surgery. There were no deaths in either group. And in patients who didn't have residual disease, that is, in patients who didn't have residual disease, we really couldn't say anything about the two different approaches, because there were no events to evaluate whether there was a difference or not between these two approaches. What we can get from this information is that probably in patients who don't have residual disease in the kind of hysterectomy, the approach may not have had an impact on the outbreaks, but the study was not designed to show that. The numbers were very few and there were no events to adequately and aesthetically evaluate this issue. In terms of the size of the tumors, as we can see here, this is a tumor of more than two centimeters, evaluating the minimally invasive versus open approach. And it was clearly demonstrated that in patients who had a tumor larger than two centimeters, the probability of residual disease by minimally invasive surgery is just over four times worse when the tumor is larger than two centimeters. When tumors are smaller than two centimeters, we can't evaluate if there was a significant statistic, because there were no events in the open surgery group. However, it should be noted that looking only at the absolute numbers, there were no residues in the open surgery group. However, there were seven residues in patients who had minimally invasive surgery, who had tumors less than two centimeters. So, again, as there were no residues, we couldn't evaluate a statistical analysis of this population of patients. And the issue of pre-conization is also important. And here we evaluate patients who didn't have conization before surgery. And in this group, the minimally invasive surgery group had almost six times worse residues than the open surgery group. So, again, a much higher residue rate for minimally invasive surgery if the patient didn't have a conization. Interestingly, in patients who did have a pre-conization, there was no difference in the closure. If the patient had minimally invasive surgery or open surgery, this is probably highlighting the fact that the patients who had a pre-conization, probably these patients had small, microscopic tumors, or the patients didn't have evidence of residual disease in the stereotomy sample. So, in these patients, there was no difference in the incidence rates when comparing the two surgical approaches. We also evaluated the rate of carcinomatosis when the patients had residual disease. And we found that when the patient had open surgery, in the residues, there was no case of carcinomatosis. But if the patient had a residue with minimally invasive surgery, 24% of these patients showed up with carcinoma. We also published the adverse outcomes of the LACC study, and this is a previous publication in the American Journal of Obstetrics and Gynecology, and also on the quality of life. In short, Andreas reported the adverse events and showed that when comparing minimally invasive surgery versus open surgery, there was a general incidence, similar to adverse events between operating rooms and post-operating rooms. In addition, Michael Fromovitz published on the assessment of quality of life, again with multiple assessments and a score system, and found that in that population of patients, the quality of life post-operating was similar between the two treatment groups. So, a compound of the two results, the recurrence rates were higher, the survival rate was worse than the disease rate, it was worse for radical and minimally invasive stereotomy, and the quality of life was similar between the two groups. So, what happened since 2018, when it was originally published in the New England Journal of Medicine? There were several institutions that analyzed its data to determine if there was any difference in its assessment, and consistently, most of the institutions found that the oncological outcomes were worse for minimally invasive surgery compared to open surgery. This is a publication that exemplifies exactly this in Europe, where the laparoscopic approach had a worse survival rate than the open approach. Interestingly, in this publication, I also want to highlight how many patients had laparoscopic group residues. 43% of them were carcinomas. In our study, we found 24%. Another study that I would like to highlight is that of Javier Madrina at Mayo Clinic. It is a study that basically highlights the fact that if a specialist surgeon has the same outcomes as a novice or someone who is still studying, obviously, this is an institution that has a vast experience with radical robotic stereotomy, and in this study, they found that patients subject to radical robotic stereotomy had a lower survival rate, free survival, and overall survival, compared to open surgery. Again, results very similar to the LACC study, even in a highly experienced institution in minimally invasive surgery. This is a publication by Juliana Rodrigues, from Latin America. In institutions in Europe, which also showed that the minimally invasive approach was associated with a worse outcome in a study of more than 1,000 patients. One of the questions that also arose was, what was the change that occurred in practice in the United States? And this is a study that analyzed what happened since the publication of the LACC study in patients in the United States. And as you can see here, the LACC study was initially presented at ESGO in March 2018, and then published in November 2018. And as you can see here in the blue line, in this graph, there was a gradual decrease in the number of minimally invasive surgeries that are carried out in the United States. This is a reflection of the 12 months after the LACC study. It was presented at ESGO in terms of standards of practice of minimally invasive radical stereotomy. I invite you to read this article that was published in the New England Journal of Medicine about the effect of a randomized controlled study on cervical cancer surgery, and it also showed a significant decrease in the rate of radical stereotomy carried out by minimally invasive surgery in the United States. This is the most recent publication on the National Data Bank of Internship Samples. More than 6,000 patients for Kojima-Su and Jason Wright. This was a study, okay? And what it showed was that the rate of minimally invasive radical stereotomy decreased significantly since the presentation of the LACC study at ESGO. And they also note that there was an initial increase in the number of complications due to the change in a traditional, minimally invasive approach before the presentation of the LACC study for an open approach after the presentation of the LACC study. Interestingly, what they found was that the use of minimally invasive stereotomy decreased significantly by 63% until December 2018, which was only a month after the publication of the LACC study. The rate of minimally invasive surgery was 18%. So, there was certainly a notable increase in complications in patients with open radical stereotomy. Now I'm going to talk about the vaginal protection maneuver. This is a maneuver that was published by Christopher Koller and his team. In their study, they showed that by doing a vaginal protection maneuver, we can thus avoid adverse oncological closures on a laparoscopic or robotic approach. So, there are a number of centers where they are suggesting that the vaginal protection maneuver can be beneficial. But this was a retrospective study where we don't have a lot of information. We only have information about the indications for the vaginal protection maneuver and we only know the patients that were included in this study for the vaginal protection maneuver. Similarly, the SUCCOR study by Luis from Spain also showed that the minimally invasive approach was worse compared to the open approach and certainly this was consistent for both residues and death incidence. One of the things that they evaluated was the vaginal protection maneuver and one of the things that they highlighted was that by doing the vaginal protection maneuver, the results can be very similar to the open approach, as we can see here in the blue and red lines, and certainly the outcomes are significantly worse if there is no protective maneuver. So, that does point out the issue of tumors being the same. I would also like to talk about tumors with less than two centimeters because some have suggested that if a tumor is microscopic or very small, maybe the patients can still be subject to a minimally invasive approach. This was a study by UPAL in several institutions in conjunction with the University of Michigan and what they found was that in patients with tumors less than two centimeters, the minimally invasive radical stereotomy had a lower survival rate of diseases compared to the open approach. A study in China also showed a survival rate of diseases by the minimally invasive approach when evaluating patients with less than two centimeters. In other words, a series of studies also showed that in less than two centimeters, the outcomes were worse. This is a study by Giovanni Scambia, where he showed that in patients with more than two centimeters, there was definitely a difference, but in less than two centimeters, there was no difference, and so they suggested that the laparoscopic approach could be viable in patients with less than two centimeters. But be careful when evaluating these studies. These are retrospective studies that have a very low number of patients. They conclude that in the study to show a significant difference between an open laparoscopic surgery in cases of tumors less than two centimeters, a larger sample needs to be evaluated. This is a study by Dr. Dimitri with a much larger sample, more than 2,000 patients. In this study, they showed that patients with minimally invasive surgery have a larger overall survival rate than those who had an open laparoscopic surgery with less than two centimeters. And certainly, the fact that in less than two centimeters, the minimally invasive approach can still have worse oncological outcomes. This is a subsequent analysis where he compiled all the publications with less than two centimeters, and this favors the open approach. And then, finally, laparoscopic disease. If we have negative margins, there is no difference. And what we have when it comes to data in patients with stage 1A tumors, patients with stage 1A tumors, and this is a study of nearly 2,000 national data banks in almost 2,000 patients who underwent this procedure. And the overall survival rate was comparable, similar, between laparoscopy and laparotomy. One of the very important things to emphasize is that in this study, the vast majority of the patients, three quarters of the patients, were really in stage 1A. Therefore, they were not even patients requiring radical stereotomy and low-risk patients. About 80% of them did not show signs of lymphatic or vascular disease. It is important to note that when evaluating these very small tumor studies, the vast majority of patients did not need radical stereotomy. This was a meta-analysis with more than 9,000 patients by Roni Nittetti of MD Anderson, and what this study showed is that when evaluating all these introspective studies, the results, there were still outbreaks in favor of open surgery for recidivism in death by various causes, highlighting the fact that the approach of minimally invasive surgery was associated with a higher risk of recidivism and death compared to open surgery. In conclusion, it has been shown that there are worse oncological outbreaks with minimally invasive surgery, outbreaks similar to complications, relative outbreaks, and quality of life. All guidelines support open surgery, and minimally invasive surgery should only be used in clinical studies. Currently, there are three ongoing studies, one from China, one from Europe, which is the RAC study, and another from the United States, ROC. They all evaluate open surgery versus minimally invasive surgery. These studies are ongoing, and we will probably have their conclusion in 5 or 10 years. And finally, I would like to mention that the vast majority of the guidelines suggest that open surgery should be a new care standard. Thank you very much to all of you. That was great. So, thank you, Dr. Ramirez. Thank you very much. Dr. Ramirez, please remember to ask your questions in the Q&A. So, what's going to be a standard of care for surgical management? So, what do you consider the surgical management standard for pre-stage cervical cancer, 1A2, 1B2? And what is the classification? The classification is based on the 2018 classification, called FIGO. Let's wait a few seconds for the audience to respond. Okay, so just wait about, we are now closing the poll. Okay, so Pedro. Hi, Raytan. Hey, how are you? Good to see you. Great to see you. So when, can you see the polls result? Yeah, I saw the results and, you know, I think it's very reflective of what we're seeing also here in, in the United States where most institutions now offer the open approach for patients with cervical cancer. And I wanted to just obviously start addressing some of the questions in the interest of time because... It's very important to emphasize that a conization is not indicated they teach this all the way for lesions that can be seen in the cervix. Now, if you can see the lesion, you don't need a conization, just a biopsy because it's not a microscopic tumor. So it's very important in this case not to misinterpret the literature that suggests that coni patients will be more successful because we anticipate that coni patients, but not necessarily because they have a conization, but because they are microscopic tumors when compared to the exophytic tumor. The suggestion in this case is not to do a conization to reduce the size of the tumor. The term is debulking conization in English. That doesn't make sense. It shouldn't be the message that should stay. Another question, what if we do a vaginal protective maneuver for open stereotomy? That's what we do when we put the clamps under the cervix to do the colpotomy. That in itself is a vaginal protective maneuver. So that's an open surgery, the tumor is not exposed to the open stereotype. Another question from the chat. Would you offer a minimally invasive surgery in a tumor of less than 2 centimeters? The answer is no. In our institution, we don't do any minimally invasive surgery for cervical cancer. In tumors less than 2 centimeters, we have the results of the CONSERV study. This study showed that possibly patients won't need a radical hysterectomy. So the next question is, would you do a laparoscopy in patients less than 2 centimeters? That would be a simple hysterectomy. We don't have data to suggest that this is safe. We know very well the CONSERV study. 94% of patients do laparoscopy. But it's a study of 100 patients. It's not very big to define if minimally invasive surgery versus open surgery is different. We also need to wait for the SHAKE study, which will compare radical hysterectomy versus simple hysterectomy in this type of patient, if the patients will have minimally invasive surgery. So we need to wait for the results. We have a question in the chat as well. It says, what was the justification for the conicalization for microscopic tumors? It wasn't part of the LAC study. In fact, it didn't need a conicalization for macroscopic tumors. A major tumor doesn't need a conicalization. A patient with a major tumor shouldn't have a conicalization. In other words, it wasn't part of the LAC study. Does it make sense to use knowledge and radical hysterectomy to define it? Well, we offer patients with open hysterectomy within our institution, based on the results of the LAC study. The IRTA study is also a multicentric study. We don't see any difference between open and minimally invasive. But again, it's a retrospective study, and we don't know if it's a prospective way. Let's be sure. We do open hysterectomy to be sure. So does the conicalization make sense to you? If hysterectomy is not a good option, well, if you believe that the patient will have positive radiation criteria, you don't think that doing a pre-conicalization of radical hysterectomy makes sense. No, it doesn't make sense. So basically, the way you have a tumor that is large, the way we approach it, and according to the guidelines, is that if you have a biopsy, and you have cervical cancer, and you don't see anything in the exam, then we do a conicalization for the patient. Now, if you have a patient who has any injury of any size, and you do a biopsy, you don't need to determine if it's invasive or not invasive. This patient has a larger injury, so this patient, we need to do a radical tracheotomy, but we don't do conicalization when we have larger tumors. We have two more questions in the chat. The first is about the survival analysis. The question is if we can do the stage 18 to evaluate the results. Yeah, certainly the FIGO staging has changed. Very well. The FIGO staging has changed. Now, if we classify patients with less than two centimeters and more than two centimeters, the survival analysis doesn't need to change because we're not including patients larger than four centimeters in the LAC study. So, basically, the results, the survival stagings will be the same. The interpretation of these studies will be like this, but again, we only have this stratification of less than and more than two centimeters. The study was not designed to evaluate more than two centimeters. We didn't have an important analysis for those two groups of patients. Again, in the FIGO staging, the FIGO staging doesn't need to change the results because we didn't include patients with more than two centimeters. I guess we have a clear, more clear communication using the name of FIGO. We have a much clearer communication with respect to the FIGO staging. The rate of carcinomatosis is much higher than I asked. The rate of carcinomatosis is much higher. We have some literature that also analyzes the open approach. The rates are definitely higher. It's a question that not only in the LAC study, but also in other studies, they showed, for example, in Giovanni Scambia, that 42% of the patients who had recidivism had carcinomatosis. Possibly this is related to some aspect of the progression of the disease through the abdominal cavity. This is a reason why we shouldn't do a minimally invasive surgery. which makes the laparoscopy less open. Is it because of the tumor progression or because it wasn't completely removed? Well, we didn't find a difference in terms of the positive imaging rate because of the carcinoma. And we don't know. Our study wasn't designed or designed to find the reason why. It could possibly be a tumor contamination or peritoneum contamination. Other things, or on the other hand. Go ahead, I'm sorry, go ahead. No, no, no, there is one question since you asked. Can you repeat the question? Well, if you have a positive information, you should do a laparoscopy. So, what if some people are doing, they are doing laparoscopy. If we have positive margins, we should not do a laparoscopy. There are many people who are doing a laparoscopy. They do a biopsy, a cryobiopsy. And this is what is done, for example, in Austria. What they do is an evaluation through the ganglion laparoscopy. Then they do the cryobiopsy and then they take the adhesive capacity. When we look at patients, we see patients who have a radical stereotomy, most of them do not have positive ganglions. That is, for example, in the CONSERVE study, less than 2 centimeters, the rate of positive ganglions is 5%. That is, we would do 95 laparoscopies and biopsies, cryobiopsies, which would be without need in the patient. With these 2-centimeter patients, the vast majority, we are actually exposing these patients to processes that we do not need. 2 to 4 centimeters are patients who have a greater possibility of ganglion-lymphatic commitment, which would be 7 to 12%. This commitment, when we look at these patients, our pathologists say the following, that the vast majority of these patients cannot be diagnosed through cryobiopsy because they have a macrometastasis. Therefore, they cannot see inside the section by freezing. So, now, with pelvic MRI, how much fear of having positive ganglions that you can have a surprise in the operation, we will not have any surprises with pelvic MRI. That is another thing. It is kind of connected. One is about what type of incision we should do ophthalmologically, right? So, what would be the type of incision? Then we have another type of incision, then we have another type of decision. Another question that is linked to this question is the following, in patients with ETMC greater than 40, you do the open, you take a completely different approach and go to the lymphatic ganglions. When there is no clear commitment, that is, when it is simply a suspicion. With respect to the first question, we do a Fanny Steel incision, a Fanny Steel, or a medium-line incision for open radical stereotomy. The patient leaves the surgery the next day and two days after the surgery, they go home. For obese patients, it is important to emphasize that MD Anderson, that in MD Anderson, we do not do minimally invasive surgery for anyone, even for overweight patients. We do an open radical stereotomy and, obviously, we analyze all the factors for any other patient. Pre-surgical images, MRIs, but, again, we do not do minimally invasive surgery in MD Anderson for cervical cancer. Now, the last question, with respect to the lymphatic ganglions, right? Now, do you do an open radical stereotomy? Do you do an open radical stereotomy? And when you have a lymphatic ganglion that is not metastatic, do you do surgery or chemotherapy? If we have suspicion or non-specific, we have a dysfunction. So we talk to the radiologist to get a biopsy through magnetic resonance or TEC. They do this biopsy for us before the surgery, guided by TEC. If it is cancer, they do chemotherapy. We have a lot of questions here in the chat. I would like to ask Pedro to answer all of them, but unfortunately we don't have time. We need to continue. Thank you very much, Pedro. It was an excellent presentation. In our next presentation, we will hear Dr. Lopez Blanco speaking about cervical cancer in pregnancy. Dear colleagues, I'm Dr. Lopes Blanco, gynecologist, oncologist at the National Institute of Neoplastic Diseases in Lima, Peru. This time I'm going to talk about cervical cancer and gestation. I want to thank the IGC International Cancer Society Committee. Thank you very much for inviting me to give this talk. It's a great pleasure. For this talk, I don't have a conflict of interest. It's important to emphasize the magnitude of the cancer of the uterus. We know that it's a problem at a high level in Latin America, being the second place of incidence with more than 56,000 new cases per year and the third place of mortality with approximately 28,000 new cases per year. In relation to cervical cancer and gestation, approximately 0.05% to 0.01% of all gestations could occur. Although its presentation is very rare, it's a very common neoplasia during pregnancy. Among the most common malignant neoplasias diagnosed during pregnancy are breast cancer, followed by cervical cancer, hematological neoplasia, and melanoma, which together represent 70% of cancers associated with pregnancy. Here is a graph that shows the cancers associated with pregnancy and their frequency. The breast cancer is in first place, and the uterus cancer in second. In this next graph, we have the neoplasias, which are more frequently associated with gestation. Within them, we can see cervical cancer, and in red and different colors, we can see the stage of the disease. Here we can see that cervical cancer is associated with gestation, is diagnosed, or presents itself in the initial stages, which is different in women who are not pregnant, where the diagnosis frequently occurs in advanced stages in Latin America. In this slide, we see the frequency of gynecological cancers associated with pregnancy, where the first place is occupied by cervical cancer, followed by ovarian cancer, ovarian cancer tumors, and vaginal cancer. Other general aspects that we should consider is that, as we saw in the previous slides, the most common associated gynecological cancer, gestation, is cervical cancer of the uterus. It is rare and, therefore, its treatment is challenging and complex, because the treatment could determine or harm the mother's oncological prognosis. It should also not be ignored, the risk of teratogenic, as well as the possible delay of intrauterine growth, even the death of the fetus. From the moment we study the gestation of the disease, the use of chemotherapy or radiotherapy for the treatment of cancer. Another important aspect that we should take into account is that the prognosis of the cancer of the uterus is the same for pregnant and non-pregnant women. If we have a patient diagnosed with cervical cancer associated with gestation, these patients should be sent to specialized centers in multidisciplinary management. It is important that during the treatment of the cancer of the uterus, you define the prognosis, the treatment of the oncologist, gynecologist, oncologist, radiotherapist, pathologist, oncologist, neonatologist and obstetrician-gynecologist. And the important thing is the patient. Listen to the patient. And within this, it is also important to see the context of the regulations or laws of each country or of each region for the treatment. Within the studies of the extension of the disease, when we have a patient diagnosed with cervical cancer, it is important to consider that these studies could affect the development of the fetus in the future. Exposure to radiation should not exceed more than 100 milligrams. It was reported that the incidence of cancer attributed throughout life to a dose of radiation above 50 milligrams is estimated at approximately 2% if the fetus has been exposed after 15 weeks. But a precise quantification of this risk for cancer in the future is almost impossible. So, given this, the non-ionizing imaging procedures, such as ultrasound and pelvic magnetic resonance, are safe techniques for staging in pregnant patients. As for gadolinium-GD, we do not know the therapeutic effects on the fetus. Therefore, it is not advisable to use it in pregnant women. To consider the handling of cervical cancer associated with pregnancy, we must take into account whether or not there is a ganglion commitment, the size of the tumor, the physiological type, the stage of the disease and the gestational age, which are important factors to determine the definitive procedure. We have several handling options. One of them is to delay the treatment until the end of gestation. Another option, the second option, would be to terminate the gestation. For a definitive cancer treatment, the third would be a surgical treatment, with the preservation of pregnancy, such as conization, simple or radical trachelectomy, with or without lymphadenectomy. And neoadjuvant chemotherapy is the fourth option that could be used to delay or prevent the disease from progressing, preserving the gestation until the fetus is viable. There are several consensus, several specialist guides. I bring here the most significant, where there is the ESMO, which is not published, and is from 2019. And within that, there are mainly two groups, group 1, in less than 22 weeks of gestation, where, according to stage 1 to 1, for example, there could be only a simple conization, if the PLV, vascular lymphadenectomy, is negative. In tumors less than 2 cm, with 1 to 1, with PLV, positive vascular lymphadenectomy, or 1 to 2, or 1 to 1, it is indicated if the lymphadenectomy is pelvic. If the ganglions are negative, it could be in observation or chemotherapy. If the ganglions are positive, it is recommended to terminate the gestation. This includes micrometastases. In stages 1 and 2, pelvic lymphadenectomy and chemotherapy are recommended in advance. In stages 1 and 3, chemotherapy is recommended in advance. Pelvic lymphadenectomy, due to controversy in these stages. And in stages 1 and 2, well recommended in these guides, complete the gestation. It is important to note that some specialists, in relation to pelvic lymphadenectomy, have a lot of controversy about the use, right? And in the other group, in group 2, with women with more than 22 weeks of gestation, in the initial stages, chemotherapy is recommended, neoadjuvant versus observation. This will also depend on exactly which week of gestation the patient is in and the risk that she may or may not progress the disease. In larger stages, stages 2 and B, it is recommended to terminate the gestation. This in the vast majority of cases. Or, optionally, if the patient decides to continue with pregnancy, give adjuvant chemotherapy until the end of the gestation. Within the previous slides, this is a summarized graph of what is found. I am marking in red, in women in the initial stage with cervical cancer associated with gestation. As long as they have less than 22 weeks of gestation, right? So, pelvic lymphadenectomy is recommended. Why is that? Because these patients could stay in observation. And to stay in observation, as they are initial stages, it could reduce the risk of ganglion commitment. But, I repeat, pelvic lymphadenectomy, as part of the surgical staging in patients with cervical cancer and gestation, is quite controversial. And I emphasize, in green, the use of adjuvant chemotherapy in different alternatives and scenarios. We will see here a little more of chemotherapy in neoadjuvant during pregnancy. And there are many series published on this, small publications of cases. But, however, there is always a fear about what are the effects of chemotherapy on the fetus, right? It is important to emphasize that chemotherapy is contraindicated in the first quarter of pregnancy, as it can be associated in 10 to 20% in congenital malformations. After the 14th week of gestation, a series of drugs could be harmful, as part of chemotherapy, including toxins, platinum agents, anthracyclines, etoposits and bleomicin. There are several studies that talk about the rate of general fetal malformation, and these indicate that they are similar to the general population. Therefore, chemotherapy can be used after the first quarter of pregnancy. It is also important to consider that the window that must be given since the last cycle of chemotherapy must be three weeks before delivery. With the intention of recovering the bone marrow of the mother and the baby, especially in premature babies. It is also important to consider the ototoxic effects of cisplatin. This will depend on the dose, and apparently some guides or specialists recommend that carboplatin, compared to cisplatin, is safer. The relative toxic myelotoxic effect of the etoposit and the cardiotoxic effect of anthracyclines. Long-term toxicity data, after the exposure to chemotherapy in children with child cancer, have shown, in some cases, that there was cardiotoxicity, in other cases, irreversible hearing loss, neurocognitive problems, endocrine commitment, and, to a lesser extent, secondary neoplasia, and a general increase in morbidity. But it is not yet clear whether the exposure to intrauterine chemotherapy may be similar to the effects of exposure in small children with cancer. That is why it is important to monitor this population of newborns exposed to intrauterine chemotherapy. This is a large series that was published by Professor Arunachalam in 2015, where he recollects more than 39 cases of cervical cancer from different small series published, where more than 60% are patients with cervical cancer with advanced stages. The vast majority of these patients had a response to chemotherapy, allowing the pregnancy to be prolonged, and the vast majority to be concluded. The most widely used drug in this report was cisplatin, although the duration and schemes vary between the authors. One of the conclusions of this article was also fetal well-being, which was not compromised in any of the cases that were announced. There are also other series that talk about the safety of the use of texanos during the second and third trimesters of pregnancy as a safe option. A recent publication was made in 2018, which includes 39 studies or reports of cases, 88 patients with cervical cancer, in which chemotherapy was administered during pregnancy. There were 88 births, of 84 gestations, where there was obviously the gestation of twins and triplets, where all the births, approximately 80%, were completely healthy at birth. At the end of the monitoring, although it was not a long monitoring, approximately 20% of the patients were diagnosed with recurrence of cervical cancer, and almost 90% of these died due to recurrence. But one of the observations was that the overall average of survival was not reached, not even the overall average of global survival, nor the average of free-of-progress survival in this series published by a very short monitoring. These results showed that platen-based neoadjuvant chemotherapy could be a favorable option for cervical cancer treatment in women during the second and third trimesters of gestation. We published a retrospective study of cases in Latin America of neoadjuvant chemotherapy associated with patients with cervical cancer. It was a multicentric Latin American study. The aim was to describe the oncological and obstetric outbreaks in patients diagnosed with cervical cancer during pregnancy who had a successful birth after chemotherapy and derivatives. As I mentioned, it was a retrospective study. The inclusion criteria were patients with a histological stage of cervical cancer, with a stage 1b1, a stage 4a, according to an article from 2019, which were associated with pregnancy and received chemotherapy from 2007 to 2018. There were about 12 centers from 5 countries that participated in this study. In the end, 33 patients were collected, where it is important to note that the average age range was 34 years. The vast majority of patients, 60%, were in stage 1b and locally advanced, almost 40%. The most frequent histological type was the Scamoso carcinoma, 90%. The vast majority of patients were diagnosed in the second trimester of pregnancy, 33%, in the first trimester and 6% in the third trimester. The most frequently used imaging studies were magnetic resonance with ultrasound in about 90% of cases. Among the drugs, the most used schemes were carboplatin and Paclitaxel in 60% of cases, cisplatine and Taxol in 21% of cases and other schemes. Toxicity was reported in only 18% of cases. In relation to the response of neoadjuvant chemotherapy, there was between the stable, compound, partial and complete response, in about 70% to 75% of cases. Among the obstetric results, there were obstetric diseases in only 12% of cases. Almost 70% of cases did not have obstetric diseases. The gestational age period was 35 weeks. All patients ended their delivery by cesarean section. The average weight was 2.340 kg and the average height was 45.5 cm and other characteristics, but they were comparable to the previous reports of the cases. Referring to the definitive oncological result of the patients. About 33% of patients did radical sterectomy and chemotherapy plus radiotherapy in 67% of patients. Among the patients who were subjected to radical sterectomy, half went into labor and the other half, 50%, went postpartum. Of the patients who had radical sterectomy, the patients who needed adjuvant treatment were only 25% of them. Summarizing the age range, the average was 34 years in our series of cases. In this age range, 90% was carcinoma epidermoid, 60% in stage 1b, 60% in the second trimester of gestation, and the most used chemotherapy schemes were carboplatin associated with Paclitaxel and cisplatin plus Paclitaxel in 20% of cases. The number of chemotherapy cycles was between 3 and 4 and 86% of patients are currently alive. What were the weaknesses of the study? It is a retrospective study, although it is true, with small groups of patients. But, above all, it was the largest retrospective series published so far. The monitoring was not long, it was short monitoring. The selection criteria were quite heterogeneous. The strong point of the study is that it is a multithentric, retrospective study of cervical cancer with gestation, in which it was found that neoadjuvant chemotherapy is an alternative to advance fetal viability without affecting the oncological results. In relation to the center where I work, which is a reference center in Peru, where we manage cervical cancer, holding multidisciplinary meetings, where different specialists participate. The scheme we use for chemotherapy is carboplatin, Paclitaxel, every 21 days. We started chemotherapy after 14 weeks of gestation, and for this, for the staging, we use the magnetic resonance of the abdomen and pelvis. We do the restaging after the end of pregnancy, and if it is operable, we defer the surgery after six weeks of the end of gestation. As final recommendations, the cervical cancer treatment associated with gestation is a challenge. It is complex, because the treatment can fall directly under the oncological results of the mother, and it is also important to consider the theratogenic effects of the oncological treatment. That is why patients should be sent to specialized centers for multidisciplinary management. Within this management, conduct, it will be important to take into account the opinion of the mother. It will also have a direct impact on the treatment of the patient's gestation age and the stage of the disease. The evidence we have is based on case studies, retrospective studies, and the opinion of specialists. Currently, prospective studies would not be viable in this group of patients. In this way, we will always have the level of evidence that is not so high compared to a phase 3 prospective study. Chemotherapy with cervical cancer can be treated with neoadjuvant chemotherapy. This is an option of treatment to end gestation without compromising the oncological results and with minimal effects on the newborn. But more monitoring studies of these patients are necessary. Patients who have been exposed to intrauterine chemotherapy. Thank you very much for your attention. If you have any questions, I would be here to answer them. Thank you so much, Dr. Lopez. Let's do a series of questions and answers. Very well, this would be a question for all of you. Some things have to be considered when we evaluate a pregnant woman with uterine colorectal cancer. In your opinion, what would be the wrong option? So, we will wait about 30 seconds for answers to come in. Let's wait about 30 seconds. For now, you answer the question. OK, can we see the answer, the results? We can see the results. Very well. We are seeing here a split answer. Are you able to see the answer, Saldo? Well, thank you very much, Reitan, for sharing the survey. Well, first of all, what we have as evidence of colloidal uterus associated with gestation would be more case reports, specialist opinions. And as we can also see in some reviews, for example, the majority do not even exceed 100 cases. So we're going to have a lot of discrepancies, and obviously none of them, none of the recommendations have a strong evidence. This is a bit complex to handle. The handling of these patients, who have a high volume of patients with coloidal uterus cancer, we have a radiologist, a therapist, to handle this type of patient. We have another question, Aldo. How many cycles of chemotherapy? How many cycles of chemotherapy does a pregnant woman need to have? Well, if we indicate chemotherapy after 14 weeks of gestation, on average, up to fetal maturity, we apply between 3 and 4 cycles of chemotherapy, sometimes up to 5. This is what we have seen in the reports. But it is also very important to consider a three-week window before ending, that is, before giving birth, because of the bone marrow, so that it can be recovered, not only in the mother, but also in the fetus. This is a question from Horacio Moncho. Is there a wait for six weeks after cesarean section? And for some specific reason, why wait so long? Well, in fact, the system does not report this much, but it reports the problems resulting from the depression of the bone marrow. But since we have been working, we have not had these problems, in fact, in neonates. When do you have ulcerative colitis? What do you do, Aldo? Let's assume that there is a suspicion of a metastasis. Do you consider doing chemotherapy, do a radical stereotomy, or better a nephrectomy? And then, oh, you're talking about if there is a mass in the ovary. It is important to consider that in ulcerative colitis, most reports talk about keeping the gestation in the initial stages. If we suspect that we have a cancer, if we have a mass that we are suspecting, we need to give priority to the mother and consider as if this patient was not pregnant. She has to undergo a surgery to rule out that this tumor is or is not primary ulcerative colitis. We do a laparotomy and we study the mass to know if it is a rare metastasis, that it is a metastasis and the prognosis is bad. And we will give priority to the mother's treatment in this case. Dr. Hussein is asking, now, if we have an early diagnosis of ulcerative colitis, and the indication is a radical stereotomy with the fetus, what would be the gestation age to do the stereotomy? With the fetus in situ? Yes, fetus in situ. Due to the laws that have to do with local laws, for example, in Peru, abortion is indicated when there is an imminent risk, risk at the time of pregnancy by the mother. Now, in this case, pregnancy, that is, the risk of the mother is not at risk because of the early cancer. So, in fact, it is not recommended. Neuro-assistive chemotherapy, which is coming and is very popular, the use, in fact, is ... We do not handle things like that. What we do is that if we have a patient in an early stage of ulcerative colitis, we have a tumor of less than 2 centimeters and a unit of gestation in the first trimester, what we do is observe the gestation in a way to avoid the progression of the disease. That is, we observe the patient. If at some point we see that the tumor is growing and the gestation is greater than 14 weeks, we could opt for chemotherapy. One last question, Aldo. The complications in patients who are pregnant and have ulcerative colitis, bleeding, for example, of the tumor, how do you handle this during gestation? Obviously, with compressive treatment, that is, we have several cases with ulcerative colitis associated with gestation. Well, there are not many, but with mechanical treatments they will not respond, so we need to see, because it is at risk of the mother's health. But, that is, how to get him to terminate the pregnancy? That is, it complicates the handling a little. If we see that there is a bleeding that cannot be contained, with mechanical processes, then it will actually complicate. Then we opt for the possibility of using radiotherapy. Now the question is, why do we do stereotomy six weeks after terminating pregnancy? It is a question that is asked a lot, and it is also a discrepancy between specialists, but we do radical stereotomy immediately after cesarean surgery, due to the risk of bleeding. If you have a good set of blood banks, and specialists in radical stereotomy, you can do it. But often in hospitals, those general hospitals, we do not have these equipment. That is why we recommend that it be after six weeks of gestation. It will not change the prognosis. The risk of bleeding will certainly be lower, and mainly it will not have any impact on the oncological prognosis. Perfect, Aldo. So, I'm sorry, but we have to move on. We have another issue with the transmission of Dr. Lema. So, we have an intervention of Dr. Lema, then we have five minutes, and we will be right back in five minutes, and I will see you in five minutes. I am the Scientific Director of the Clinica Oncologia Storga in Medellín, Colombia. I wish to thank the IGCS and my dear friend René Pareja for this invitation. I would like to thank the IGCS and my dear friend René Pareja for the invitation. In the next few minutes, I will discuss the state of the art of chemotherapy in cervical cancer. These are my conflicts of interest. I am Dr. Mauricio Lema. According to the guidelines, non-metastatic cervical cancer is treated with chemotherapy or radiotherapy. Systemic therapy has become the main stage of treatment in metastatic residue and recurrent disease. The addition of bensamicisumab to chemotherapy in the first line, or as a single agent in subsequent lines, has become a more recent significant advance before the era of immunotherapy. Based on the GEOG 240, a Phase III study compared chemotherapy alone versus chemotherapy plus bensamicisumab in the first line scenario. The advantage of global survival was demonstrated in the arms of bensamicisumab with an average global survival of 16 months, an improvement of three months in relation to chemotherapy alone. Cancer cells can proliferate when T cells are asked for the so-called immunological checkpoint. One of these T cell inhibitor systems is due to the interaction of PD-1 in the T cells and PD-L1 in the two, the tumor in the infiltrating monoclonal cells in the tumor, including lymphocytes and macrophages. This interruption of the PD-1 and PD-1 axis can potentially restore the antiviral activity of the T cells. This can be achieved with monoclonal antibodies against PD-1. This can be achieved with monoclonal antibodies against PD-1 with pembrolizumab, nivolumab, bastilimab, cambrelizumab, and semilipimab and cambrelizumab. In many situations, they are also very effective. Immunological checkpoint inhibitors are the basis of current immunotherapy. In cancer, immunosuppression has been presented with a tumor activation mechanism in neoplasms related to HIV, including cervical cancer. This includes tumor infiltration by immunosuppressive monoclonal cells and PD-L1 superexpression. This immunosuppressive medium constitutes the basis of immunotherapy as a strategy in cervical cancer. As is often the case in oncology, the paradigm shift begins at the end of the clinical spectrum, such as second or third line therapy. If effective, they move constantly to first line therapy and even to the metastatic scenario. We will briefly discuss some trials of immunotherapy beyond the first line in cervical cancer. Keynote 158, a clinical study of myocardial infarction, which included a cohort of 91 patients who protected or were intolerant to first line therapy. The patients received Lissomar membrane every three months for up to two years. The primary outcome was the global response rate. The main characteristics of the patients included an average age of 46, that is, 1.65% PD-L1 positive in 83%. Close to 80% of the population of treatment received more than one line in the metastatic scenario. In total, the objective response was up to 80%. In total, the objective response was reached in 14 patients, that is, 14%. There were five complete responses. All responses occurred in the PD-L1 group based on the combined positive or CPS score. Anti-PD-L1 is studied in the tumor sample made up of tumor cells and mononuclear cells. The formula will provide the number and PD-L1 is considered positive if CPS is greater than 1. Returning to the Keynote 158 study, the free progression and global survival were 2 and 9.4 months respectively. The toxicity was acceptable. As a result, the FDA approved PD-L1 positive in cervical cancer in the second line and the line. BALSTILIMAV, another anti-PD-L1, was tested in 160 patients in the Phase II study. We can see the characteristics of the patients in this study here on the slide. Again, there was a preponderance of young and symptomatic patients, most of them previously treated for metastatic disease. The agent was effective as shown here on the graph. The objective response rate was similar to the Keynote 158 and no new security signal was found. It is important to emphasize that there were some responses in the populations of negative patients for PD-L1. Also in the second line scenario, we have the CLAP study from China. In this study, 45 patients were registered and 41 patients received the anti-PD-L1 Camrelizumab plus Apatinibe, an anti-angiogenic agent. The response rate of this combination was 55%. This combination was associated with a toxicity rate of 71%, possibly derived from the anti-angiogenic agent. The characteristics of the patients in these three studies are similar. These are the main outcomes, with the exception of the general response rate in the CLAP study, which includes another potentially active component. The combination of the anti-PD-L1 and anti-angiogenic agent resulted in this small cohort of 11 patients treated with Atencilumab, Atenzolizumab, and an anti-anti-PD-L1 agent. These patients were treated with Atencilumab, Atenzolizumab, and an anti-anti-PD-L1 agent. The study was considered negative. The only phase 3 study in the pre-treatment scenario would be Empower Cervical 1. Semi-PRIMAB, another anti-PD-L1 monoclonal antibody, was studied in comparison with the researcher's choice, the chemotherapy. The primary endpoint was global survival. The study recruited 608 patients, including a significant minority of adenocarcinoma. Empower Cervical 1 was positive, with a 3.5% improvement in global survival in relation to the control arm. The average global survival of the experimental arm was 12 months. The benefit of survival was observed in both histologies. But the benefit appeared to be limited to the positive population for PD-L1. Notwithstanding, the authors concluded that Semi-PRIMAB was active regardless of the PD-L1 status. Based on these trials, you can conclude that there are a multitude of active anti-PD-L1 agents in the population of patients with pre-treated cervical cancer. Now let us move to the first-line configuration. The Keynote E826 is the only phase 3 study published so far in the metastatic scenario of first-line cervical cancer. The study recruited 617 patients with metastatic cervical cancer recidivated or recurrent without prior systemic therapy for metastatic disease. The patients were stratified according to the expression of PD-L1, among other variables. The control arm was Padam chemotherapy with Pembrolizumab. Pembrolizumab was added to chemotherapy in the experimental arms. And the two primary species were free-of-procreation and global survival. The Keynote E826 surveyed a young population of about half with symptomatic disease. Almost 90% of the patients described were positive for PD-L1. An improvement of 35% in free-of-procreation survival was observed in the arm, Pembrolizumab, in the analysis intended to treat. The overall response rate was also higher in the arm of Pembrolizumab, 65% in the experimental arm and 50% in the control arm obtained complete or partial responses. The toxicity related to the treatment were similar in both arms, with adverse immunological reactions expected in the arm with Pembrolizumab. Even though the results are still immature, global survival is higher in the arm of Pembrolizumab. The overall survival in this arm is estimated at 24 months. An important improvement in relation to the 16-month mark established by the GOG240 study. The Keynote E826 is a study of one year of practice and the FDA approved Pembrolizumab chemotherapy in patients with PD-L1 positive cervical cancer in the first-line metastatic scenario. This is the state-of-the-art. There are several ongoing trials involving immunological checkpoint inhibitors in cervical cancer. Some of these are exploring the addition of anti-PD-L1 or anti-PD-L1 agents in the locally advanced, that is, in the necessary that is not metastatic. I am very proud to say that in our center we were able to register five patients in one of them, the Keynote A18, with Dr. Diego Moran as the main investigator and with the help of René Pareja. Many other options are also being studied. In conclusion, anti-PD-L1 monoclonal antibodies demonstrate anti-tumor activity as unique agents or in combination with patients with advanced cervical cancer. Regulatory approval in the United States for Pembrolizumab was granted to positive patients for PD-L1. Pembrolizumab was included in the NCCN guidelines. If regulation and access were not a problem, I would incorporate anti-PD-L1 agents using these trial algorithms. In short, I would use Pembrolizumab in first or second-line therapy in patients with PD-L1-positive disease. And I would even consider the use of Semiprimab if approved in the second configuration of second-line in patients even without PD-L1-positive disease, because there is some evidence of activity. But if approved, it is almost impossible to predict. And with that, I would like to thank you for your attention. Well, thank you, Dr. Lema. Let's begin with some questions and answers. Let's see the question that came from the audience. Sorry, the question for the audience. Immunotherapy in cervical cancer seems to be effective. It was proven to be effective in Phase III studies, randomized and controlled in the following scenarios. Choose one of the scenarios in which it was approved. A few seconds for you to finish answering the question. We are waiting just a little bit for what people can vote. They said it was a PD-L1 positive disease. In this way, what do you think? Because there were different answers. Dr. Mauricio says that, in fact, the right answer is the right answer that I expected from the public. It's the cytotherapy. It looks like he has problems with the connection, but let's go on. But I understand why the audience chose number B. In most studies, they have a very clear demarcation about the answers of the patients, in PD-L1 patients. But not only in this patient. There are some data that even responds to the negative PD-Ls. Specifically, in the CLAB study of this MIPLI-MAP. There were some answers that were important in negative PD-L patients. The answer I expected was C, but it could also be B. We have a question from Dr. Lozano, who says, do you believe that B-pacizumab is beneficial when we use pembrolizumab in the first line? Or do you use it without ambeva? I don't have access to pembrolizumab for cervical cancer in my country. So this is a very hypothetical question for me. But I wouldn't add pembrolizumab to pembrolizumab. I would simply use chemotherapy plus pembrolizumab. If you have any questions, you can send to the Q&A feature. It's in the bottom of the screen. What if I can say something before any question? Mr. Mauricio keeps saying that he wants to make a comment. One thing is certain, and that is that immunotherapy has an important role in cervical cancer. Especially in those cases that are already advanced. And I'm almost sure that the studies that are being published, carried out, sorry, at this time, will also be positive. Not published, but carried out. What are the future perspectives for the future on immunotherapy in cervical cancer, doctor? And how far is this from patients in Latin America? How do you see the future? He says there are some access problems, because these agents are expensive, says Dr. Mauricio Lema. This can be a barrier to be able to incorporate these agents. But at least in Colombia, we believe that the Colombian regulatory agencies will eventually include pembrolizumab. Because this has already been used in other diseases, in this way, I think it would be the standard of care. But this takes two years in Colombia, while it is approved by the FDA and then approved by the INVIMA, which is our regulatory health agency here in Colombia. So, I would say that by the year 2023, I think we could use it for the first line. Whether it is used only or with chemo radiation, as it is being used in the studies. We also have a gap for private practice, says Mr. Ribeiro. But as I said before, we hope that in 10 years from now, it will go from the private sector to the public sector of health care, says Dr. Ribeiro. And another question is, how do you feel about the financial issues and about the immunotherapy? So, this is a question that needs to be answered, right? Dr. Miguel Correa, do the results of the immunotherapy have better results in some kind of special histology? This is a good question. Actually, no. There are some histologies that are included in all the studies, but it appears to work better than others. The only thing is, I don't know if it is a good question, but there are some histologies that are included in all the studies, but it appears to work better than others. Obviously, the scaly tumors, but it also works in adenocarcinomas. The only one I wouldn't use would be in small cells, in the neuroendocrine. In this histology, I probably wouldn't use it, but in the others, yes. A question from Argentina, who says, congratulations for your presentation, she says, and the question is, what would be the appropriate time to wait between radiotherapy for the localized management and the administration of pembrolizumab? Dr. Lema says that pembrolizumab, at this moment, is not expected to be used after radiotherapy or with radiotherapy, okay? But the time I use pembrolizumab in other diseases, when I'm going to use it, is approximately two weeks after finishing the radiation. Due to concerns that are not related to pembrolizumab, I use it as Lapsin, when I use cytotoxic agents. But we can use pembrolizumab very close to radiation therapy or with radiation therapy, including Dr. Lema, Dr. Ribeiro says that we have little time and we have two questions for Dr. Lema to answer for us. Well, the next question is, in which patients with metastatic cervical cancer would you use bevacizumab? He answers that practically everyone would use bevacizumab, would use the GOG240 criteria, says Dr. Lema, because they don't have access to pembrolizumab. And I think that the GOG240, it changed the practice in this way. At this moment, I would add bevacizumab to almost all chemotherapies, at least first-line chemotherapies. Most of the time, I use platinum plus paclitaxel as the main axis. Also used in the GOG240 study. Last question, Dr. Chow, he asks if there is any recurrence of cervical cancer, a stage of cervical cancer after 1, and bevacizumab, what do you suggest? If we are now in second line and there is a progression, I would probably consider other agents. But we know that the issue is not here. It won't be good for the patients, it won't go well. We had some answers with a combination of platinum plus gempsinabin. I think that gempsinabin doesn't add too much, so I give a little bit of platinum and a little bit of platinum with gempsinabin and I already got some good answers. It's a successful treatment in these patients. Thank you very much, Dr. Lema, Dr. Ribeiro, and we will continue with our next presentation with Dr. Anuja Jinger about advances in radiation therapy. Good morning, everyone. For those who know me, you know I always start with a story. So, as we all know, radiotherapy is the main treatment for advanced cervical cancer. The principles of radiotherapy say that it is necessary to include all the microscopic extensions and you have to give a sufficient dose. So you need to give between 85 and 90 gray, two points of OCTD, which I will talk about today. Brachytherapy is very important and should be used whenever possible, but the time of such treatment should not exceed 56 days. As I said, let's start with a story. The beginning of the story tells us that cervical cancer can only be cured with radiotherapy. These are data before chemotherapy that show that radiotherapy alone works very well, even for stage 3 disease. Only with radiotherapy for stage 3 disease resulted in a local control rate of 70% and a global survival rate of 50%. So, only for stage 3 radiotherapy works. However, radiotherapy caused complications. For 10 years, about 4,000 patients were monitored with degree 3 or higher toxicity in all radiotherapy patients resulting in 11% complications in the long run. And as we all know, in 1999, several studies showed that chemotherapy was better than radiotherapy alone. As you can see, the benefit was greater in stage 1 and 2, but it also benefited stage 3, but only by 3%. So, the big question is why are we here? How can we improve? So, the conclusion is that chemotherapy is better than radiotherapy, but the benefit was not as high in stage 3 and there is still room for improvement in stage 2. We also know, by modern data, that it is a rate of distant visceral residue from 14 to 21 after chemotherapy. A rate of paraortic excision from 9 to 12% after chemotherapy and a 13% pelvic failure rate. And as I said, radiotherapy increases toxicity, especially intestinal. So, the question is how can we improve, which is what we are going to talk about today. How can we improve, then? The main advances we have in oncological radiation are advances in technology. This was our old field, radiotherapy with 3D formation, which we all know. What was the disadvantage of this radiotherapy? What caused intestinal toxicity? It was that we treated the whole intestine with the total dose. So, this is where modulated intensity radiotherapy comes in, IMRT, which you certainly already know. But I would like to talk about it again because it really is one of our major advances. This is a randomized study that analyzes the IMRT in postoperative cervical cancer and dendrometer cancer. The patients were treated with IMRT or 3D formation. And what we found was that the results were the same for both. Very good. But the most important thing is that the patients who received IMRT and what the study analyzes were the results reported by the patients. More importantly, the patients who received IMRT reported less diarrhea, less use of Imodium or Lomotil than the patients who received 3D formation during the treatment and a year after the treatment. They also really reported less urinary toxicity specifically after the treatment and three years after the treatment. So, the conclusion is that IMRT reduces the diarrhea reported by the patients, both acute and late, both GI and GU, without affecting local control or global survival. So, IMRT has become the standard for both postoperative cervical and uterine alcohol treatment in the United States and in Europe. The use of EMBRACE-2 is a prospective study based on data that only used IMRT-BMAT in the patients. The goal of EMBRACE-2, for which we should have results soon, is to reduce toxicity and improve local control. So, moving on to brachytherapy, because we are talking about improved technology. As I said, brachytherapy is very important in the treatment of cervical cancer. A database study showed that there has been a decline in the use of brachytherapy since 2003, and this is really when the IMRT came in. This database showed that patients who received brachytherapy had better results than patients who did not receive brachytherapy. So, the key point is that brachytherapy is very important in the treatment of cervical cancer. Here we can see the decrease in the use of brachytherapy leads to a decrease in survival. So, brachytherapy is very important. So, what are the advances in brachytherapy? Many of you know that we went from 2D to 3D and then to 3D magnetic resonance, which includes computerized tomography and magnetic resonance. The advantage of image-guided brachytherapy is that you can see the tumor and you can see the normal anatomy. So we're leaving 2D and going to 3D, even in brachytherapy. So advantages of image-guided brachytherapy is that we can define the disease, we can define the normal tissues, we can define the dose based on what we see and not in bone reference points or simply from where the disease is. This is just an example of a magnetic resonance in a patient with cervical cancer and that we, as radiologists, define. What we see here is what we call the intermediate risk disease, which would really be point B. Here we see the high-risk CTB and this is the colo-ductorum plus the perimetrium. And this is the JBTB. Now we can see, define exactly what we have to give the dose. We can also see the normal tissues. Here is the sigmoid, here is the rectum, the bladder. So we know exactly where the doses are. And, in fact, the data shows that image-guided brachytherapy improves local control, improves global survival and reduces toxicity. But the biggest advantage is that we can see the disease. Here we can see that it is a residual disease and if we do a standard treatment, we could give an overdose to the sigmoid or rectum and this is where the interstitial needles come in. You put the needle directly and treat the disease without treating the normal tissue. Here is another example of where the needles come in. We can see that it is a residual posterior disease. If we only treated it with the voids in tandem or anase in tandem, we would have to push the dose outwards, which would have treated the sigmoid or rectum. By putting the needles, we can load the needles without touching the normal tissue. So, again, another advantage of image-guided brachytherapy. So, we can treat a patient individually. In fact, we have shown that interstitial brachytherapy plus the voids in tandem or anase in tandem improves local control. But the key is that it improves toxicity. It improves the toxicity of the bladder and the intestine. So, it is a combination of interstitial intercavity. These are data comparing the intracavity alone versus the more interstitial intracavity. We can see that it reduces rectal toxicity and bladder toxicity as well. So, the big advantage of image-guided brachytherapy is that we are starting to add more needles to the areas where we need to reduce toxicity. We also changed our idea about which doses we can give compared to what ICR did. We are therefore changing the dosage. We can see that the rectal dosage was reduced. So, now we have to keep the rectum below 65. We are analyzing the vaginal dose and we increased our dose for the CTV of high risk. So, what image-guided brachytherapy did is that it helped us to identify tumors either using an external fish or in brachytherapy. It has allowed us to identify the tumor. It has allowed us to identify the microscopic disease well with normal tissue. And it has allowed us to adjust the dose around the areas that we want to reduce the normal dose for normal tissue. So, it allowed us to reduce acute toxicity in the long term and to improve local control or maybe increase the dose, I don't know. So, IMRT, VVT, VMAT became practically the external fish pattern for uterine colic both in Europe, in the United States and in other places where it is available, including India. Brachytherapy is now the golden standard for all patients with cervical cancer if it is available in their country. It helps us to identify the disease and it helps us to adjust the dose. Interstitial is recommended. And in the EMBRACE 2 study, 30% of the patients should have been treated with interstitial. And in fact, the long-term study data shows that 70% of the EMBRACE 2 patients were treated with a combination of intracavity and interstitial. This is really one of the biggest advantages we had in radiotherapy that allowed us to improve the quality of life of our patients and to reduce toxicity. So, where else can we take this technology? Is brachytherapy important? Yes, it is important, as I said. What happened in the United States was that when IMRT arrived, the use of brachytherapy was reduced, but it did change the survival rate. IMRT or SBRT can be used if we can't use brachytherapy. And there are some situations where we can't use it. The technique would be to take 30 gray in fractions of 5 to 6. This is just an example of SBRT instead of brachytherapy. And, yes, we can give formal doses using SBRT for the uterus that are comparable to brachytherapy. The disadvantage of SBRT is that brachytherapy gives hot spots inside the disease, which increases the dose for that disease, which SBRT does not. It is much more conformational. So, in fact, there is probably less dose for the disease using SBRT than using brachytherapy. But the data show that SBRT can be used. But we can see that the local control is definitely much lower than if you use brachytherapy. But it is reasonable if there is no brachytherapy or if the patient cannot receive brachytherapy because of a bad response. So, in conclusion, brachytherapy is the right treatment. But SBRT can be used instead of brachytherapy if there is a bad response or if there is no brachytherapy available. But it has to be done carefully and has to be planned. So, what is our biggest and most advanced improvement in radiotherapy? And that is really in the treatment of metastatic disease. So, one, and this is actually a really interesting study because I think this is really relevant, especially for most of the world, in metastatic disease. This is actually a national study based on cancer data that analyzed the definitive rRT-PEV. The definitive rRT-PEV, but brachytherapy. In patients with metastatic disease, there were 3,000 patients and of those, 900 received only chemotherapy and the rest received chemotherapy plus radiotherapy. And what they found in this database study was that patients who received definitive rRT chemotherapy had a better overall survival than patients who only received chemotherapy. So, as you can see, this is the chemotherapy rRT arm compared to the chemotherapy arm. The patients with chemotherapy rRT had a much better overall survival than the other group. And this is just matched. These are matched based on factors. Again, rRT chemotherapy was better than chemotherapy in survival. So, even in metastatic disease, adding definitive rRT chemotherapy in some patients would really improve their overall survival. But what about all of the metastatic disease in general? This is really very important, both in the era of chemotherapy and in the era of Bevacizumab. So, all the data really really started from these four studies that were presented between 2017 and 2019. And all these studies of non-gynecological tumors showed that patients with oligometastatic disease who received systemic therapy plus radiotherapy for these oligometastatic diseases, the patients who received radiotherapy came out better than patients who received only systemic therapy. The point is that these are all very small studies, 49 patients, 29 patients, 99 patients, but it showed that maybe treating these oligometastatic diseases with radiation and ablation and adding systemic therapy may be better than just systemic therapy alone. And this just shows here a case presentation of a patient who was treated with definitive rRT chemotherapy. Here we can see the brachytherapy guided by image and external effect. The patient fails, a failure in the liver. We can see the liver lesion treated with stereotoxic rRT. Another liver lesion treated with stereotoxic rRT. There were also scratches here and here, all treated. The patient then received systemic therapy and he is alive five years later and doing very well. It's just an example, but it's a very good case. There's actually data that shows that the treatment of oligometastatic disease can improve survival. And this is just one of many studies that analyzed patients with cervical cancer. This is a study done in Italy with 83 patients with cervical cancer. Most of the cases were lymph nodes, but about 44 had metastatic disease. The median dose was from 35 gray, 10 gray, to 60 gray in five fractions. The complete response was almost 60%. 46 patients had a complete response. 29 patients had a partial response and 16 patients had a stable response. The toxicity was very mild. 19% had mild acute toxicity and 5% had late toxicity. The conclusion of this study was that there really was a link between the complete response to improve local control, free-of-progress survival, and global survival. Another thing that they concluded was that this is systemic therapy. It could take up to two or three years if the patient did recur before they needed systemic therapy again. The last conclusion of this study is that ECBRT can be combined with other systemic therapies, especially immunotherapy, which really can give us a much better systemic response and maybe global survival, and improve local control, global survival, and free-of-progress survival of the disease. So, what would be the future? We are analyzing several studies that are randomizing systemic therapy versus systemic therapy plus ECBRT in one to five metastatic locations. NRG is doing this. EMBRACE is also doing this. ESTRO is also doing this. Systemic therapy can be anything, chemotherapy or immunotherapy, but they are looking at systemic therapy versus systemic therapy plus radiotherapy. I think these studies will really help us understand the role of stereotoxic radiotherapy in all metastatic diseases. There are also several studies in the registry that we hope will help solve this with a larger group of patients. So, adjuvant therapy. I'm really going to briefly talk about adjuvant therapy because we really have two new studies that I think we need to discuss. We need to discuss where the future of adjuvant therapy is. Very well. The first one that we need to talk about is Outback. This is just a statement from the Outback PI that basically says that Outback confirmed that chemotherapy and radiotherapy by themselves is the best treatment for patients with advanced local cervical cancer. Adjuvant chemotherapy should not be used at this time. So, really interesting results in a study with 800 patients. Very interesting results. The next study, which is very recent, and we don't have the complete details, is the Cala study. It is a large study that analyzed immunotherapy with RT chemotherapy versus RT chemotherapy alone. A very large study. The results have just come out. This is a statement from Dr. Monk that basically showed that there was no statistical significance in the addition of immunotherapy to RT chemotherapy versus RT chemotherapy alone. So, again, the pattern continues, even in the Cala study, that RT chemotherapy is the standard treatment for patients with advanced local tumors. In summary, advances in radiotherapy, imaging-guided therapy, either external fascia or brachytherapy, is where we are and where we are going. We are also going to more accurate local treatments, basically ECBRT. This is going to be relevant in the oligometastatic disease, but it can be used in special cases when brachytherapy is not allowed. But what we really need to do is move forward to find more studies that are using radiotherapy with new exclusive therapies. We need to find out how we can combine these two, either in metastatic configuration or advanced local. Thank you again for the opportunity. I hope I have explained well the advances in radiotherapy and I hope you have a wonderful morning. Thank you very much. Thank you so much, Dr. Gingham. It was a wonderful presentation. I have lots of questions, but we will begin this Q&A. Thank you, doctor, for your excellent presentation. Let's start with the question for the audience. What would be the wrong option? According to the principles of radiation therapy in cervical cancer, choose an option. The wrong option. We have a few more seconds. We will wait a few more seconds for everyone to answer the poll. We have lots of people responding, so... We have many answers here. So, let's say, okay. So, I guess you sent your message to Jinger. Do you want to comment on that? I think your message has arrived. Do you want to comment on these results? I think your message has been passed to everyone. 62% of the people said that the answer is the letter B. That is, people did listen to my presentation. Everyone was attentive and my message arrived to the participants. This is well said, Doctor. And Dr. Ribeiro said he has a personal question. After that, we can move on to the questions. How far do you believe radiotherapy is to be an option? How far is it to be an option for initial tumors? Do you feel that the day will come when we can finally say, well, let's do chemo, radiation and preserve fertility? Dr. Anu already said that the problem is that we still have to treat the uterus. So, I'm not sure that we are close to that, because we need a margin. In this way, we are far from preserving fertility. But I think we can preserve and preserve the ovaries, yes. And we are going to be closer and closer to that. In these patients, says Dr. Ribeiro, with steroidal colorectal cancer, which does not treat the uterus, with therapeutic therapy? I think so. It was a good question. Dr. Anu already said that it would be important to explore this topic. Mr. Ribeiro said that you can send your questions through chat, through questions and answers. And I have another question while other questions come to you. We know about the studies of the 80s and 90s, where it says that radiotherapy, we had, where we had many complications in radiotherapy. Do you think that using the new technologies, how different would it be from the past? Dr. Anu already said that it is very different. I want to be honest with you. One of my colleagues, who you probably know, who used radiation on her own, she is a colleague of mine, she says that many patients must have stereotomy, followed by chemo-radiation. Our new technologies cause less side effects. And some young patients, it is much better for them, the chemo-RT surgery, because we give less dose in the vagina. So our toxicity has improved a lot with the new technologies. And some patients, it is better. Chemo-RT surgery for less toxicity in the vagina and less doses too. So there may be some patients who benefit from the three types of treatment. And we have advanced a lot in this type of treatment. Excellent question, fantastic. Dr. Ribeiro says... Yeah, no, I agree. I think some studies we should definitely do again. And I'll be honest. She says yes, we should do some studies again, right? And in young patients. Going back to radiation, if we think they need radiation, we do the surgery because we apply less dose in them. We are not giving 80 in the vagina, but 50 or 45, which is a significant dose for these patients. We have another question, says Dr. Ribeiro. It's an interesting question, he says. He says, for patients with metastasis, large, with more than 10 centimeters in the ovaries, do you think, would you take into consideration that the radiation is still efficient, effective? Or would you consider doing this before chemotherapy? Or what would you do then? Dr. Anuja says that the last slide that I showed you, ladies and gentlemen, showed that patients, I would do chemotherapy first, okay? But I think that often it's chemotherapy first. Because this size in the ovary is very large. Maybe I would take it out first. I have a patient now, that this patient had a tracheotomy and came back and had a metastasis in the ovary of 10 centimeters, a metastasis that was already 2 or 3 years old, so the surgeon took it out. And I'm applying radiotherapy after surgery, as soon as the stereotomy was done, and the ovarian metastasis in the ovary, as soon as we could take it out, it would be fantastic. Otherwise, it would be with chemo. As soon as I can't control an ovarian mass of 10 centimeters, so the idea would be surgery, and after that, radiation. We have a lot of questions here. What would be your opinion? I'm asking about your opinion on oligometastatic disease. So, we do treat oligometastatic disease, and we're treating quite a bit of it. But we are coming back, you know, when we've done chemotherapy, and the patient comes back with metastatic disease. So, I think radiation therapy, ablation for 5 or less injuries, I think that would be a good answer, but systemic therapy. We have another question here. That's an interesting question. I'm not sure where this question came from, and I think it all depends on the dose that you're giving with the brachytherapy. We should know a little bit more, we should have more details to be able to answer that. Unfortunately, we don't have time. I know there are a lot of questions. I'm going to try to answer them as we move on to the next presentation. Thank you very much, Dr. Ribeiro, and let's move on. I'm going to invite Dr. Renato Moretti, Dr. Renato Moretti, surgical treatment in advanced cervical cancer. Hello, everyone. Good morning, everyone. It's a pleasure. It's a pleasure to be with you and represent my institution in this great webinar on gynecological cancer to talk about the surgical treatment of cervical cancer. I would like to thank the organization and Dr. René Pareja. It's a great privilege for me to be able to be here alongside the most important names of cervical cancer treatment. My name is Renato Moretti Marques, coordinator of the Department of Gynecology and Robotic and Gynecological Surgery at Israelita Albert Einstein Hospital in Brazil, in São Paulo. I'm a member of the International Society of Gynecology and I'm also a mentor of the Mentoring Program. I have no potential conflicts of interest in this presentation. The focus of the presentation will be on cervical cancer, which represents 604,000 new cases per year and 341,000 of these patients will die in the course of the year. 80% of the cases are in low and medium-risk countries. The FIGO stage, the FIGO stage system, we can see here the local extension, the local extension of the FIGO system, the local extension of the FIGO system, we can see here the local extension in the clinic with imaginology and also the status of the lymphatic ganglions. We also evaluate with PCT, among other images. The treatment pattern in cervical cancer of stage 2b to 4a is chemoradiation based on many important studies. Oncologists should be aware of the prognosis and the reason why there are failures in this treatment, local extension, renal failure, bleeding. The duration of radiotherapy, response to radiotherapy, infovascular invasion, these are very important factors for the prognosis and that affect the prognosis of the treatment. The initial radical surgery or the initial radiotherapy is a personalized radical sterectomy. It is a personalized radical sterectomy and here we evaluate the impact of surgical approach. We evaluate the impact of surgical approach and here we evaluate the impact of surgical approach which is not well accepted due to the toxicity of the treatment which is not well accepted due to the toxicity of the treatment that the resources are low and the radiotherapy could have a surgical approach, no option treatment. As far as the pelvic treatment, a primary pelvic interaction is an extremely rare situation with no stage IV-A, and the difficulties to manage the central disease, there are difficulties to manage the fistula, it's complicated, there is a high rate of complications and less survival. Neoadjuvant chemotherapy was evaluated in two randomized studies, more or less in 1,250 patients, and it was published in 2018. Dr. Gupta and in 2019 Dr. Kamper, using different chemotherapy schemes, but in both studies there is no improvement in survival, in the groups exposed to chemotherapy, followed by surgery, compared to the standard groups. We can see here the two groups, several authors, including the main investigators, they conclude in this way that neoadjuvant chemotherapy should be reserved for these research stages. The FIGO stage we are seeing here, the higher the stage, the higher the probability of metastasis. We can see here the metastases that can be diagnosed through a PCT, and here we see the specialty of the specification, false negatives and false positives. The German group, Dr. Christel Keller, their proposal for a long time was that the radiation field tracing surgery, first the surgery and then the radiotherapy, the surgical staging versus clinical staging, so the proposal was the surgical staging versus the clinical staging, as being pre-treatment in chemotherapy in local cancers. We can see here the surgical treatment, and if we have positive lymphatic ganglions, we can in this way expand the radiation field. There is no difference between the surgical and clinical staging arms, but the authors, they found better results in the surgical group, in the 2B stage. Here we have several authors and studies as well, Dr. Shinoda, Michael Frunovitz, among other groups. The surgical staging as more than 20% should be taken into consideration, especially in the local context, where the PCT is not available, in those low-resource contexts. The concept of advanced procedures, the sterectomy, after the chemo-radiation, unfortunately just two randomized metanalyses, unfortunately, there are only two authorized clinical studies, which are available, and this type of treatment is the radical sterectomy after chemo-radiation. With the advanced procedures, in this way, the pre-treatment, the debulking, the lymph nodes are larger than two centimeters. The results of concurrent chemo-radiation are expected to sterilize this huge mask, lymph node album mask, is almost 70%. This kind of volume of tissue is going to sterilize this huge mask, C75 gray, the general volume for a general is 60 gray, the survival of five years in patients where they do the debulking of the lymph nodes, the survival of five years, procedures of salvation in this pelvic interaction. We can see here the patients who benefit from this, the survival after this pelvic interaction for cervical cancer, we can see here in the graph, patients who have more favorable cases with cervical cancer, we can see here in the graph, patients who have more favorable cases with the free survival of disease, it's two years, when the tumor is less than 5 centimeters, also depending on the experience of the cancer center, as a contraindication, are metastases visceral at a distance, and invasion of the sciatic nerve. And at the end of my talk, we could discuss, isolate the retroperitoneal, we can talk about the metastasis of the lymphatic ganglia isolated in the aortic section and the retroperitoneal region, corresponds to the second most frequent place in the cervical region. The PCT is necessary to exclude the metastasis, for isolated metastasis, radiotherapy is done or debulking of the lymphatic and surgical ganglia, and this can extend the survival in approximately 30%. This is really important to describe. This is a late-paraortic symptom. It's not very common. But it's a rare situation when you have this survival after paraortic debulking as a bad thing. Other sites that are known lymph nodes are positive. This is the survival series. It may be lymph nodes. It may be a surgery. And when there is a recurrence on my part, it can be done chemotherapy. We don't have enough numbers of patients to be able to prove this. In this way, the messages that we take to our home is that advanced local cervical cancer is present in most cervical cancers in low- and middle-income countries. Here, my chemotherapy for advanced local cervical cancer is from 2015. It's a 2B4A stage. It's a treatment pattern. Gynecologists and oncologists must be aware of the reasons for the failure of the treatment. Using chemotherapy only when radiotherapy is not available. The pre-treatment of aortic ganglion dissection with radiotherapy reserved for FIGO 2B and pelvic positive ganglions. Advanced sterectomy after chemotherapy and radiotherapy must be done for confirmed disease persistence histologically. The debulking of lymphatic, aortic and pelvic ganglions must be discussed in a council and before chemo, radiotherapy or surgery. Pelvic interaction is a good strategy with a healing purpose after a pelvic recurrence with a metastatic ganglion disease. Thank you very much, Dr. Moretti, for your attention. Very well, our first question for the participants. Are contraindications for performing on exenteration procedures? No. So, you have to choose one of them. So, we have a few more seconds. Okay, let's see. So, do you want to make a comment on that? Yes, hello, Haytham. Absolutely, this scenario of central recurrence is one of the most important for surgical approach in localization of cancer. If you have more disease than the central disease, probably you won't have a surgical margin change. In general survival rates are really low. If you have lymph node metastasis or dissemination of the pelvic or visceral metastasis, it wouldn't be a good scenario to do the excentration. In the same scenario, what are your limits for, let's say, in that scenario? Well, a tumor where the patient was treated with chemotherapy and radiotherapy and now has a central tumor. What would be the limits for the ectomy or the excentration? Or there are no limits? Good question. When we can see the good results of the surgical recession, we're talking about after the chemotherapy. The surgical margin has to be one centimeter, in this case, depending on the extent of this condition, especially when this condition is before the chemotherapy and in the anterior part of the vagina. So, if we have a very large volume and a central disease, we don't indicate radical hysterectomy to alleviate this situation. We prefer the pelvic excentration. The rates of surgical complications, especially the complication of the urethra or the vagina, these rates are very high after the chemotherapy and radiotherapy, especially if we are in a place that has low resources in terms of available chemotherapy and radiotherapy. It has to be very, very central. Not a procedure that is easy to do when the patients have residue. And Dr. Dos Reis, our good friend, is asking, do you consider the free progression of the disease a reason for the pelvic excentration, six months, nine months? I forgot the reference of a study, but it's a great study that describes the overall survival after the pelvic excentration. This has limits, especially in ovarian cancer. If the residue is before six months, we are, in this case, talking about a high-risk disease. And we don't get the full cure of the patient. Especially after 24 months, the residue comes up, and that can be the time to do that pelvic excentration. Dr. Rissell also has a question. Due to the risk of lymph node capsule leakage during surgical release, is it feasible to perform a conventional treatment, chemo radiation and brachy? And could you repeat the question? Due to the risk of lymph node capsule leakage during surgical release, is it feasible to perform a conventional treatment, chemo radiation and brachy? And could you repeat the question? If there is a persistence of the disease after the initial treatment, that would be a great question. Because one of the limits of the metastasis of the lymph node, when we don't have a good radiological evidence that will describe the limits of the lymph node, when we have the central part of the lymph node change with necrosis, the risk of all this, of breaking the oncological barriers during the procedure, is one of our limits. So, it is also possible to consider the fact that if we have a large mass, with a vascular invasion, with a duretic invasion, and if we don't have limits to prescribe the surgical resection without affecting that lymphatic mass, then we can do chemo radiotherapy. However, the concept of imaging is not well established. As well, before the metastasis of the lymph node is well established before chemo radiotherapy, if it is not well defined in the literature, possibly the most important thing to do during the surgery is to check if there are any margins that can be treated without affecting these oncological barriers. Dr. Berotta has another very good question, related to exenteration and rescue surgery after chemo radiotherapy. If you have a persistent disease after radiation, would you indicate a radical hysterectomy or, in this case, would you prefer an exenteration? Well, I already talked a little bit about this during my presentation. Possibly, if we have some signals with the image, and we have the clinical tests before doing the chemo radiation, including the anterior part of the vagina, if we have a mass that is very, very large, with radiological signs, with edema in the bladder, possibly these patients can be treated with pelvic exenteration. However, if there is a low volume and a very focused disease in the central cervix, we could consider a radical hysterectomy as a good way to rescue. In countries with low resources, would you consider a radical hysterectomy as a replacement for brachytherapy? Where there is no... In countries or in places... For example, because there are many countries that don't have this option. There are also rich countries that have limited access to that. In this way, in places where access is limited to brachytherapy, would you replace it with surgery? Dr. Anuja, Dr. Anuja, what do you say? She says that in Mexico there is a study related to this, says Dr. Anuja. They did phase 2 and now they are in stage 3. And analyzing the radical hysterectomy after external radiotherapy and there are good results. These studies are being very successful. They were doing a study, phase 3, authorizing patients for brachytherapy or radical hysterectomy. In this way, it is very interesting to see the data, says the doctor. But if we don't have access to brachytherapy or if it takes three months to consult, for those who give you the consultation, the radical hysterectomy, then it would be a good option after external radiotherapy. Dr. Anuja, can I add something about what you just mentioned? Dr. Renato keeps saying that we are talking about when there is no brachytherapy resource and after external radiation. A patient, for example, another scenario, a patient who has no anatomic condition to do brachytherapy, would you consider radical hysterectomy? Would it be a good option for this situation? The doctor says, look, I don't know. The question is, if we can't do brachytherapy, can we do hysterectomy? It would probably be for the same reason, says the doctor. If we can do hysterectomy with negative margins and less complications, of course. The other thing, the other option would be to do an interstitial plate, if we can't use the tantroides. If you sometimes think you can do it, the chance of doing a radical hysterectomy is also difficult. Dr. Ribeiro says that, unfortunately, we don't have any more time. We must end the session. This is fantastic. Excellent discussion. Unfortunately, we must continue. This is all the time we have for today. We would like to thank the program, Dr. Fernando Maluf, Renê Pareja and Dr. Aldriz, who made all this possible. We would like to thank all our speakers for all their knowledge. And we would also like to thank all of you, all the participants, for being here with us in this session. The recording will be available on the IGCS website. Remember the second part, which will be here in eight days, it will be next Saturday, at the same time. And I would like to remind all of you of the IGCS meeting in New York. Thank you very much and see you next week. Thank you all very much.

advanced cervical cancer

treatment approaches

chemotherapy

radiotherapy

surgery

personalized treatment plans

immunotherapy

Latin America

pregnancy and cervical cancer

multidisciplinary management

imaging studies

neoadjuvant chemotherapy

image-guided brachytherapy

radical hysterectomy

pelvic exenteration