candidate for me here in the United States and what type of radical hysterectomy am I doing today and in what setting or at what time should one consider neoadjuvant chemotherapy prior to surgery and what are the some of our current research addressing the patients with cervical cancer in particular in low resource settings. So I think to me the right candidate it's a patient that has a 1A2 to 1B2 the 2018 FIGO staging of squamous adeno maybe small cell neuroendocrine tumors and in a time set after concurrent chemoradiation therapy they have a small central disease. Keep in mind that it's not right after the completion of chemoradiation but many weeks month later still have a persistent disease that's central smaller than two one may consider radical hysterectomy. Typically I'd like to you know do it in a healthy patient that has has some mortality of one percent or less and in the United States we're seeing a lot of obese patients. So actually my new partner came to me and told me that in Alabama they don't operate on anyone that has a BMI greater than 35 and I think it makes sense. It's not that more obese patient carries a higher death rate but it's just harder to do the surgery need longer instruments you take longer time maybe more blood loss. So if we have a chemoradiation as an option you know sometimes you may consider use like chemoradiation as opposed to surgery in a very obese patient. Obviously patient with Crohn's history of peritonitis if you want to preserve the ovarian functions surgery will be better than chemoradiation you know just want to make sure these patients are healthy to undergo surgery. So these are my the way I look at like what kind of patient I would do radical hysterectomy. So I was trained in the 90s and I did all the patients by open and then in the late 1990s to early 2000s I started doing laparoscopic radical hysterectomies and then it's not until like 2018 when Pedro Ramirez published their that published their study. I think everyone here is very well know this very well the lap while. So basically he and an international the gynecological oncologist from South America from Europe and Asia included 631 patients in a phase three trial comparing minimally invasive radical hysterectomy versus open radical hysterectomy and what they found was that that in this study 84% of patients had laparoscopic radical, 16% had robotic radical, 30% of a patient needs post-op radiation therapy but the disease-free survival at four and a half year was 10% more in the group that had minimally invasive radical hysterectomy and the overall survival was worse by 5% more in the minimally invasive radical hysterectomy comparing to open radical hysterectomy. So this study kind of changed everyone's practice on realizing a laparoscopic or robotic approach for radical hysterectomy carries a higher death weight and an open surgery will be the better way to the right thing to do. So when the abdominal versus laparoscopic radical or robotic radical based on Ramirez study showing that there was four-fold increase in death it's something like 4.4 versus 0.8% so it's four-fold increase and it kind of makes sense because if you look at about seven years ago we stopped doing we I mean you I'm sorry I should go back in this study actually look at the group of patients that had a uterine manipulator during radical hysterectomy and they found that there was a 2.4-fold increase in recurrence when uterine manipulator was used to help doing a laparoscopic radical hysterectomy and you can imagine that doing a laparoscopic surgery with CO2 high pressure it can spread all the cancer over the places increasing the risk of recurrences and seven years ago I don't know in Nepal whether you do musculation but here we were doing musculation for all the fibroids and in 2014 and there was a doctor who went through the musculation was found to have sarcoma in the uterus and people started to be aware of the the danger of musculation for uterine fibroid and and in those studies actually found about three-fold increase in death so it's kind of very similar to Ramirez four-fold increase in death using the laparoscopic approach to do radical hysterectomy so in most people's mind today an abdominal nerve sparing radical hysterectomy is the best way to do to do the surgery until we have something like newer way of doing the minimally invasive radical hysterectomy by not using manipulator not exposing the cervix into the abdominal cavity so together with a lot of people my colleague and I we wrote a commentary supporting that we really should not be doing a laparoscopic or radical like robotic radical hysterectomy but to wait until the time that we have a better technique to minimize the risk of patient dying from laparoscopic or radical or robotic radical hysterectomy and I want to point out there was a very nice video published in the international journal of gynecologic cancer towards the end of last year and that video demonstrated how to perform a type c and type c2 radical hysterectomy preserving the inferior hypogastric and pelvic spheric nerves and Dr. Mo Lim's video was really outstanding and it's available if you just google search it and you can find this video and I think he's based in Berlin, Germany. So as Dr. Pereira said the FICO staging 2018 the differences in the FICO staging comparing to the one previous one was the 1A1 it's smaller than three millimeter taking away the width of spread and in the 1B1 to 1B3 instead of 1B1, 1B2 so using two centimeters cut off two to four and greater than four and the 3C was spread into the pelvic and periodic node but identifying with the R for imaging and P for pathology. So looking back at the patient we discussed I think it's like our pathology said it's a 1A1 patient on the final pathology and I know it's because we don't have I think here the measurement really cannot be taken into account because pathology really did not confirm that I I know cervical cancer is a clinical staging but in this case probably it's not a 1B1, 1B2 cancer. So I usually like to draw this diagram with my my residents or fellows it's just easy to remember whenever I look at the staging I look at the you know stage one, two, three and Dr. Kariyosh would be telling you that when we when we do radiation you do one zone beyond that if you don't have positive pelvic nodes you have a surgical cancer that you need chemo radiation you will extend it. I know it's not that simple but you go extend the field to the bifurcation of the common iliac artery in the same with surgery right when you do radical hysterectomy you do a radical hysterectomy taking away the parametrium the upper vagina you remove the entire pelvic lymph nodes but we really do have to keep in mind in patients that have stage 1A or 2A diseases there is a 25% incidence of pelvic lymph node pertussis. So it is important when you have pelvic node spread and do radical hyst then you have to consider additional therapies. So we talk about using CT as planning and in the United States I'm sure in Australia maybe but Dubai is using PET-CT scan and this was a study actually involved in this it was an Akron study comparing comparing PET-CT versus CT scan I know it's not very clear but it did not reach a statistical significant difference between PET-CT versus CT scan but PET-CT scan is it's valuable especially in the metabolic responses and we typically we do a PET scan after concurrent chemo radiation to follow up on the patient. If a patient have a metabolic complete responses usually the better prognosis then those don't have a metabolic complete responses of course using a PET scan can guide us in following up on the patients. So Dr. Kariysh cited a very important study here by Landoni from Italy looking at patients with 1B to 2A. I'm sure most of you are very familiar with what he did was comparing radical surgery with radiation therapy for 1B to 2A. Essentially no differences in overall survival disease free survival so what this study wants to remind us is that when choosing a modality there's really no differences in outcome so if we could you know choose one best one for a patient and in the right setting and will be the better way to to to manage this patient rather than having to do both and so this comes to what what many of you know about this the GOG study back almost more than 20 years ago identifying some patients with intermediate high risk factors the GOG92. What are these intermediate high risk factors? They are the lymphovascular space invasion, deep mitral, deep stromal invasion, a large tumor diameter of greater than four centimeters. So here in table one this is a very nice table and having this condition met that you will recommend radiation therapy and the CELES trial here clearly demonstrated a reduction recurrence free survival by giving radiation therapy after radical hysterectomy patient meets these eligibility criteria. So radiation therapy after radical hysterectomy for these patients reduces the recurrence of freeze improves the recurrence free survival. And what are the other high risk factors on the GOG study 109 by Peters et al looking at if patient has positive nodes positive parametral spread or positive vaginal margins as you can see here the hazard ratio of two if you don't give in overall survival and disease free survival if you don't give concurrent chemo radiation after radical hysterectomy if you have any one of these high risk factors. So the lesson then is after radical hysterectomy if you have positive nodes positive parametria and vaginal margins. So if in the patient that we discussed earlier, if I know truly that she had positive notes by CT guided biopsy, or here a lot of time even using PET scan, not doing a biopsy, I would not have taken the patient to do surgery because I know if she had a positive note, I would do concurrent chemo radiation afterwards. Why should I put her through two surgery, right? A surgery and then two modalities, surgery followed by concurrent chemo radiation, adding on the complications and morbidities for the patient. So here's something I use, I guess, for being knowing something. I sort of, the way I remember, Seller's criteria, the S tumor size greater than four centimeters for vascular space invasion or deep cervical stromal invasion, the SSS, two out of three, you would recommend radiation or concurrent chemo radiation therapy. In the Peters criteria, is pathologically involved lymph node, parametrial or positive margin. So any one of these P's, you will recommend concurrent chemo radiation therapies. As many of you know that 85% of cervical cancer incidents and death occur in the low resource settings. And in half of our Sub-Saharan African countries, they actually don't have radiation devices at all. Can you think about treating cervical cancer with no radiation machine? And this is happening in Africa. What about brachytherapy? A lot of these countries may have for external radiation and don't have brachytherapies. So this is a real problem. So the question is, can we do neoadjuvant therapy followed by radical surgery if we don't have radiation in some patients like locally advanced cervical cancer 1B2, 2A and 2B? So here is a very nice study published by Sudip Gupta from I think Tata Memorial in India and published in JCO three years ago. So they have, this is a prospective randomized trial. One group got a neoadjuvant chemotherapy followed by radical surgery and the other group got concurrent chemoradiation. So 300 patients in each arm, the progression-free survival, disease-free survival, the yellow line is concurrent chemoradiation, the blue line is neoadjuvant chemotherapy followed by radical hysterectomy. Starting with chemoradiation, and starting with neoadjuvant followed by surgery has inferior disease-free survival. But when you look at the overall survival, there were no differences. There is a second study done by the Europeans, the EORTC study, looking at asking the same question, neoadjuvant chemotherapy followed by radical surgery versus concurrent chemoradiation from 1B2 to 2B cervical cancer. And they presented their report two years ago at ASCO meeting. And the same here, the poorer progression-free survival, the red line here is neoadjuvant followed by surgery, comparing to concurrent chemoradiation. Overall survival, however, there was no difference between the two ways of treating the patient. So the conclusion of these two very large study, although only one had been published so far, is that concurrent chemoradiation remain to be the standard of care for managing patient with cervical cancer. But I would look at it in a different way, in a setting where there's no radiation machines and neoadjuvant chemotherapy followed by radical surgery may not be a bad option because you don't even have radiation. Perhaps you can have these patients in the same overall survivals. But in this study, actually 25% of patient, they were started out with neoadjuvant chemotherapy, never really get to do surgery at all, a disease progressed. So it's not a great option, but if you don't have it, it will be an option. So in two, three years ago, we, together with many colleagues here, published a resource stratified guideline looking at how to manage cervical cancer in settings where there's a lack of radiation-breaking therapies. So we support neoadjuvant chemotherapy followed by radical surgery or surgery if there's a lack of radiation machine in the 1B, 3, 2, 2B cervical cancer. We also address a question about if there is a lack of breaking therapy, what one should do. I know in Nepal, you're really fortunate. You have a lot of, you know, you have CT, you have radiation, it's really wonderful. But in many places, even in Mexico, in the southern part of Mexico, they don't have enough radiation machine, they don't have breaking therapy. So what is interesting here, a study conducted in Mexico City, they look at comparing concurrent chemoradiation to radical hysterectomy following the radiation therapy. And so one group is standard of care, the other group is radiation up to 50 grade followed by external beam radiation. And they found in the only phase three trial showed that there was no difference. I know it's a phase two trial showed that there's no differences. And in Honduras where I used to go before the pandemic, they don't have, they only have one radiation machine and they have like a hundred patient need to be treated every day. And they have a six month wait to get to be treated. So what they have been doing is that, and they don't have breaking therapies. So the way they manage the patients that need to be treated but no breaking therapy is that they would do the external beam radiation to about 45 grade followed by additional boost to 68 grade and then do the extrafacial hysterectomy afterwards. It's kind of interesting. So lastly, I know here, everyone know about the GCIG conducting some CCR and studies and some studies are very interesting, meaningful like the SHAPE trial. So the SHAPE trial is looking at patients with very small cervical cancer, like 1A2, 1B1, smaller than two centimeter. And to compare simple hyst with lymph nodes versus radical hyst with lymphadenectomy. And so the study is closed, we're waiting for its outcome. And there's a second study by Kathleen Baylor and South Americans looking at can cone biopsy or simple hysterectomy and lymph node, lymphadenectomy be then what are the outcomes for patient with small cervical cancer and GOG278. It's actually the PRS, Dr. L. Carbon and looking at the quality of life for a study of similar to concert trials. So in closing, my right patient is 1A2, 1B2 to 2A1 healthy enough to undergo surgery, do abdominal radical surgery, radical hysterectomy rather than laparoscopic robotic today. And I support consideration of neoadjuvant chemotherapy followed by radical surgery if you don't have radiation machines in 1B3 to 2B patients. And I encourage everyone to consider cooperative group research studies. So here, what do you think this patient has? This is because after I look at your case, so I thought of, I recently published with my residents on a case, this is a Filipino lady who've been here in the United States for 30 years but she had been going back and forth to the Philippines and she came with a CITES elevated CA125 and a little laparoscopy. We know what do you think she has? Milliary. Very good, tuberculosis. So we kind of concluded that tuberculosis is something need to be treated but we know your case will be interesting to address whether one should treat tuberculosis in the lymph node if your quantified one is negative or positive, you know, something like that, it's interesting. And this patient had a negative chest x-ray too. And lastly, I just want to, I think you have a question on how to follow up on patients. There is a very good guidance from the SGO. It was published 11 years ago, how to follow up patient after treatment for cervical cancer. And I think even though we see patient on regular basis but the most sensitive way of picking up recurrences a lot of time is really patient symptoms. I think physical exam is anywhere from 29 to 75%. Cytology is actually not great and chest x-ray is not great. So we don't recommend kind of routine chest x-ray or CT scans. And, but this table here is quite good in addressing how often we should follow up patients. And there was really no evidence on a routine imaging study. If you don't have any suspicions on patients after treatment for cervical cancer. And yearly pap smear may be recommended for patient after radical hysterectomies. And lastly, I actually just, I was so impressed with Asima's next tumor board. Asima, this is amazing. So I'm kind of putting, you know, calling for everyone's attention of your tumor board to attend your tumor board. It was so amazing, Asima, your surgery. It's crazy. So anyway, thank you very much. It looks like a Netter's atlas of surgery. Yeah, that is Asima's surgery. It's crazy. Goodness. Yeah, my God. Asima, where's the bowel? No more bowels left? Did you remove everything? No, we preserved the whole bowel. It's out here, right? I'm just kidding, you're right. Linus, I have one question I had, and I always wanted an answer, and I don't know. You know, because you have seen, you know, you've done open radicals, then you switch to laparoscopic, and then, you know, we have stopped and all. I know that the evidence from the Landoney trial is from 1996, when we talk about the double modality causing more morbidity, but the group which was having a slightly bigger tumor, I think the 1B2s then, they did actually show better, or, you know, lesser chances of recurrence with the double modality in that category. It's not statistically significant, but the subgroup analysis. But I just wanted to ask you that, you know, like, 96 is pretty old, and I suppose they started doing, you know, from the beginning of the 90s and all, but when you switched into laparoscopic surgery, because, you know, I trained in radical hysterectomy from 2009, I must say, or something, and it was only laparoscopic, and yes, well, 25% of patients possibly would have gone on to receive additional radiation based on, you know, either S or P criteria, whichever, you know, but did you actually see quite a lot of morbidity, you know, when you did a laparoscopic hysterectomy followed by radiation? Yeah, no, so, you know, Dr. Nejad, actually, Farnejad, you know, Nejad Bredes, the world famous from Iran, they actually, Cameron Nejad was the one who started on using the monitors to do laparoscopy, so he actually was an amazing laparoscopic surgeon, but he was my fellow, so.

radical hysterectomy

cervical cancer

chemoradiation therapy

neoadjuvant chemotherapy

minimally invasive

abdominal radical hysterectomy