It was a good trick, thank you for that. Okay, so just one disclosure at the beginning, I'm very sorry, but I have to leave at 2 p.m. sharply because of another meeting, I have another teleconference, but don't worry, if we wish, we can continue next time. So just to stratify the risk factors for cervical cancer, because sometimes this is mixed, usually recognize these high risk parameters like barometer involvement, positive vaginal margins for invasive cancer and positive lymph nodes. And in general, I think, you know, almost everywhere, those high risk parameters are taken as an indication for adjuvant treatment. But it's much more controversial when it comes to intermediate risk. And amongst those parameters belong tumor size, stroma invasion, and the presence of LVSI. This intermediate group is not small. It accounts for about one quarter of patients with early stage cervical cancer, of course, depending a little bit on the facts like whether you do sentinel lymph node, whether you do ultrastaging, because the more ultrastaging you do, the more positive lymph nodes you have with small metastasis. So this can also influence the size of your intermediate risk group. But I consider this as a very crucial topic for the future of radical surgery in cervical cancer per se, because from one side, from the left side, from the less radical approaches, we tend to do definitely in the future, you know, the ongoing trials, which probably will be positive in terms of safety of these approaches, sentinel lymph nodes instead of pelvic lymphadenectomies. SHAPE trial will definitely be positive because already they announced that they have very low number of recurrences and they will have to change the statistics just to reach the end of the study. And so we will probably abandon radical hysterectomies and parametrectomies in smaller tumors. But then from the other side, there is in general in the world tendency to refer more and more patients for definitive chemoradiation instead of radical surgery. And it's true that if we do radical surgery and we follow it by adjuvant radiotherapy, majority of these risk factors are known before the surgery. So the question arises, why we should operate them? Why not to send them upfront for definitive chemoradiation? So that's why the question whether we need adjuvant radiotherapy in these intermediate risk factor patients is very crucial and it's very fundamental for the future of radical surgery. This is a segment from ESGO guidelines, European guidelines. This took us days to find a consensus with radiation oncologists and even with some surgeons, how to define or how to formulate the management of intermediate risk group. And finally, we agree that it's written there that adjuvant radiotherapy should be considered. But at the same time, there is an open window for the follow-up without adjuvant therapy saying that when an adequate type of radical hysterectomy has been performed, observation is an option. And besides this major decision, whether to do or not to do adjuvant treatment, there are more questions. There are really a lot of irregularities internationally, worldwide, because also criteria for intermediate risk group definition vary. And also type, it was interesting because I've pre-discussed Cervantes trial elsewhere, and there are believers in extended beam radiotherapy. There are those who say, no, no, no, it must be combined radiotherapy. And there are those who say, no, no, we have to apply the same principles as for locally advanced cancer. So it should be chemo radiation. So there are also irregularities in terms of the type of adjuvant treatment. And all the evidence for adjuvant treatment in intermediate risk comes from one perspective. Trial conducted 30 years ago in the US, GOG92 trial where indeed they showed a significant benefit for recurrence-free survival from adjuvant treatment. But this trial from our perspective nowadays was limited by many factors. The main limitations were of course, the inclusion criteria and assessment of patients and pathology, everything reflected the clinical practice at that time. So many of those would not be acceptable nowadays. And also the outcome, oncological outcome of the group without adjuvant treatment was extremely poor. Just, you know, if we take into consideration that 30% of patients who are lymph node negative patients recurrence after surgery only. So obviously this is something what would not be acceptable nowadays. And we have, and I'm very happy that Kailash is here because we together put our data from three institutions, Memorial, Melbourne, and our institution. At my institution, we have never used set list criteria for the decision about adjuvant treatment. So we did not validate patients who were intermediate risk factors. And these two other institutions in Melbourne and in Memorial, they always use these criteria. So we combine, of course, it's retrospective, it's a combination, no prospective data, but we didn't find a difference in the survival. And also what is important to emphasize that the outcome in general is very different from the GOG trial. It's not 30%, it's just a few percent of patients with recurrence. And since our communication, there have been many more joining us and revising their data and showing the same that patients with and without adjuvant treatment actually did very well and definitely much, much better than in GOG trial. And if we compare our data with the GOG trial, the difference lies not in distance, but in the local failure, so in the pelvic control. So where is the difference? Why we can even consider that our results currently are so much better than 30 years ago. Did we change so much the surgery? It's unlikely, but what is my hypothesis is that the difference is in the selection of patients. That's with much better precision, we can currently define high-risk group and remove these high-risk group from the group of intermediate risk patients because of better pathological assessment, because of sentinel lymph nodes, ultra-staging because of more than imaging. So simply intermediate risk group patient is much more precisely defined than 30 years ago. Just a few data from the SENTICS file, because it's an ongoing trial on sentinel lymph node observational one. It's not SENTICOL, which is randomized control trial, but we will have a mature data from this trial this fall, next year in the fall, but we've already can commence some figures. And it's an interesting trial because it was a prospective inclusion of more than 600 patients with early-stage cervical cancer. And what I wanted to show you or share with you is that either MRI or X-ray ultrasound was a mandatory workout. There were only 1.5%, so very few cases with positive parametria from the final pathology. While in all the reports, you can usually find 10, 15, even 20% of patients operated for seemingly 1B stage with positive parametria. But nowadays with MRI or an expert ultrasound, this risk is very tiny. So those patients are simply excluded. And also if we use sentinel lymph nodes, we can find additional 7% of patients who are lymph node positive from alto-staging. So with very small metastases, which would be normally overlooked by standard pathological assessment. So it's another advantage we currently have. And this leads us to the Cervantes trial. So after years and years of discussions with radiation oncologists, and even with many gynecologists, whether really these patients are or are not overtreated by adjuvant treatment, we decided to prepare and develop the protocol for prospective trial and somehow repeat the GOG trial. But of course, reflecting all modern technologies and approaches we have. So the trial is powered for disease-free survival, but there is secondary endpoint overall survival I will show you later. So this is the design of the trial, which is very much different from the GOG because in GOG patients were included and randomized to the trial only after the surgery. So surgery was not standardized at all. Just any type of red haste and any type of lymph node involvement was eligible criteria for the inclusion to the trial. While in the Cervantes trial, we will register patients before the surgery, then we will do a standardized surgery and then check the final histology. And if from the final histology, these patients will fulfill the criteria for intermediate risk, they will be randomized for no adjuvant treatment or adjuvant treatment. And type of adjuvant treatment will be very much inclusive. So it can be either external beam or combined or chemo radiation. Tumor size and type of adjuvant treatment will be two stratification factors. What is important, because there are obviously two modalities which will be tested in this trial, that there will be some pre-trial and on-trial quality criteria, which will be followed by independent external quality assessment committee. So this took us some time to develop charts and software and everything what we will need for this because it's academic trial, so the funding is very limited. But I hope that we really developed a good system, a good compromise for academic type of trial to do it. We will need 514 patients, so it's gonna be a challenge for us and we will definitely need an international support. And I'm very glad to hear that you are interested to join the trial because I really count on you and I hope that a few Indian sites will be willing and able to join the trial. It will really need an international effort because it's quite a narrow subgroup of patients. This is the timeline of it, so what I want to highlight is that the three-year follow-up will be needed. Then we will be able to analyze progression-free survival as the primary endpoint. And if it is not inferior to the group with adjuvant treatment, then we will continue collecting data on disease status for another three years for the final assessment of overall survival. So a lot, many years, many years to come. And now should be another part, which is about the radicality of radical hysterectomy. The reason for doing a proper radicality and classification of radical hysterectomy and the dissection. But I'm afraid that this would require at least additional 15 minutes. So Asima, tell me, I can fly through it just within a few minutes, or we can schedule it to any future meetings. What do you think? I think we would like to have a future meeting, David, because it's so important to, you know, I have been thinking about, you know, participating in the study, and I have to admit that, you know, I was trained initially, you know, in the laparoscopic radical. And then when we changed, and I think I could see more and the reason why the laparoscopic trial would have failed, because I think we were not doing the same thing all the time. And I think it's a very, very important lesson for all of us to learn, that if we have really selected this case as well, we should do a good surgery. And I think I really would like you to maybe go through it slowly and, you know, like a teaching mode. And I think you possibly need to do repeated sessions with many of the sites, I think, before they get onto it. I mean, you know, there are some sites which are really good, but I think surgical QA is so difficult. I don't know you, you know more than me, but I just think- Well, I fully agree, you know, and also, you know, these topics also would be nice to have some time dedicated for discussion because these, you know, two cases were, you know, interesting and this prolapse case, and with a statement that you see probably, you know, it's very, very rare here in our setting, but it might be, you know, quite frequent situation in your setting. So it's something very interesting for me to hear and the approach I consider very innovative and very interesting. So it's not only about lecturing, but also- Yeah, yeah. I mean, if you agree, I mean, we could carry on this meeting in-

cervical cancer

risk factors

treatment options

adjuvant treatment

intermediate risk factors