2021 Annual Global Meeting: Virtual-Plenary II: Oral Abstract Presentation

Plenary II: Oral Abstract Presentation

Video Transcription

So, I think what we'll do while we're waiting for Dr. Zola is proceed with the next presenter. And up next, we have Dr. Giorgio De Noi. Dr. De Noi, please proceed.  So, dear colleagues, good morning, everyone. In this report, we will focus on the implication of positive sentient lymph nodes in endometrial cancer.  First of all, I have nothing to disclose.  The study came up from the collaboration between two institutions, Polyclinical Gemelli in Rome with my mentors, Professor Scambia and Fanfani,  and Mayo Clinic with my American mentor, Professor Mariani, where I had the opportunity to spend my fellowship last year.  I would like to thank IGCS to give me the opportunity to share our data with you today.  As we know, the sentient lymph node is included in the guidelines, and even in intermediate high-risk, it is a valid alternative to lymph node staging.  The big innovation of the sentient lymph node is the shift to a precision surgery. We can say that an extensive surgical staging has been substituted  by an extensive pathological staging. Sometimes we know even more than what we want. And the crucial advantage of the sentient lymph node regards the ultra-staging  with the capability of detection of low-volume disease.  But which is the clinical significance of this low-volume disease? Data and follow-up are still limited.  We are still trying to understand the clinical significance of low-volume metastasis, which is still uncertain.  This is why we wanted to evaluate the clinical endistopathologic characteristics of patients with positive sentient lymph nodes,  assessing the association of those variables with the presence of multiple positive sentient lymph nodes in distant recurrence,  and also with the presence of positive pelvic lymph nodes in those women who underwent a complete lymphadenectomy.  This is a retrospective cohort study conducted at Mayo Clinic, Rochester, Minnesota. We included all patients who underwent total hysterectomy and bilateral serpingofractomy  with sentient lymph node biopsy.  Patients with at least one positive node and both endometrioid and non-endometrioid histology were included in the analysis.  Instead, patients with invasive synchronous cancer or neoadjuvant therapy were exclusion criteria.  Hematoxylin and dialysis slides were reviewed by an expert gynecologic pathologist, slides of the sentient lymph node and the uterus, together with me.  And sentient lymph nodes were classified according to the size, as we can see in the box on the right.  So, 103 patients with positive sentient lymph nodes met the study inclusion criteria. We found 36 patients with ITC metastasis, 27 micrometastasis, and 40 macrometastasis.  We found that patients with ITC were less likely than those with micrometastasis and macrometastasis to have non-endometrioid histology.  Notably, 50% of patients with ITC were FIGO grade 1, and 52% of patients with macrometastasis were instead FIGO grade 3.  Also, the type of LBSI varies significantly according to the size of the metastasis. So, patients with negative or isolated LBSI were more likely to be ITC patients  instead of macrometastasis, patients with macrometastasis which had more diffuse LBSI. And moreover, patients with ITC were less likely to have low uterine segment invasion  when compared to patients with micro and macrometastasis.  Worth of note, none of the patients with ITC in the sentient lymph node had extracapsular invasion.  Let's go to the predictors of multiple positive sentient lymph nodes.  62 patients had only one positive sentient lymph node. The remaining 40 patients had multiple positive sentient lymph nodes.  So, we found that patients with ITC and macrometastasis were less likely to have multiple positive sentient lymph nodes,  as we can see from the statistically significant percentage on the right. And the location within the lymph node, particularly extracapsular invasion,  was also significantly associated to multiple positive sentient lymph nodes.  In this picture, we depicted the multivariate analysis where size of sentient lymph nodes and age of patients were independent predictors of multiple positive sentient lymph nodes.  So, among 103 patients, the total population, 38 underwent also a pelvic lymphadenectomy. 18 of these patients had positive pelvic lymph nodes.  And the only significant risk factors that we found associated with the presence of positive pelvic non-sentient lymph nodes was the size of the sentient lymph node metastasis.  We go from 0, 50, to 65 percent. So, from ITC, micro, and macrometastasis, respectively.  Then we restricted the analysis of recurrence to the 73 patients that underwent surgery through December 2017 to allow a longer follow-up.  And we found that 18 patients had a documented recurrence. Of these, three had an isolated vaginal recurrence  and their positive sentient lymph nodes were macrometastasis in all of the three.  50 patients had distant and lymphatic recurrence. 13 underwent, received chemotherapy. 11 also with brachytherapy and external beam radiotherapy and two with brachytherapy only.  One patient's treatment was unknown and the other one did not receive any adjuvant treatment for her choice.  So, we can see in this table on the left that the risk factors associated to recurrence were non-endometrial histology, FIGO grade 3, cervical stromal invasion,  uterine serosal involvement, low uterine segment invasion, and finally, high volume metastasis. At multivariate analysis in this table on the right,  we found that non-endometrial histology, cervical stromal invasion, and macrometastasis compared to low volume metastasis  were identified as independent predictors of distant and lymphatic recurrences.  Lastly, we performed a sub-analysis of the low volume metastasis. So, focusing only on the low volume metastasis, which were 43 out of 73, 21 ITC and 22 micrometastasis.  We had 37 endometrial histologies, which is more or less 85-86%, and six non-endometrial histology. One out of six had ITC metastasis and five micrometastasis.  So, we had four that recurred, less than 10%. Overall, two recurrences were observed in patients with micrometastasis, and both of them were in patients with serious histology  who received adjuvant treatment with chemotherapy and external ambient radiotherapy. The other two in ITC patients,  one, again, with serious histology who received adjuvant treatment, and the other one in a patient with ITC endometrial histology,  grade one, with any pathologic intrauterine risk factors, who did not undergo any adjuvant therapy.  This is a sub-analysis in patients looking at the patient that did not receive any adjuvant therapy or brachytherapy only, which was 14 out of 73, the total population,  12 had low volume metastasis. Of these, one out of 12, which was the ITC patient that I mentioned before, that was the patient that recurred.  And the remaining 11 patients had a median follow-up of 3.2 years. Going to the conclusion, the identification of the disease's characteristics  harbored in positive sentient lymph nodes in combination with uterine risk factors can potentially be used, we can say, to assess the risk of recurrences  and, of course, at tailoring adjuvant treatment in the area of ultrastaging and low volume metastasis found in nodes.  We found that the risk of multiple positive sentient lymph nodes and also extensive lymphatic dissemination to non-sentient lymph nodes  is significantly associated with the size of the metastasis within the sentient lymph nodes, and also it increases with the increasing of age.  Notably, the main factors of recurrence are high volume metastasis, type 2 histology, and cervical stromal invasion. Of course, long-term studies are strongly advocated  to assess the clinical significance and long-term follow-up of this low volume metastasis.  Thank you for your attention.  Thank you, Dr. Dinoy, and congratulations.  Next, we have Dr. Paolo Zola. Dr. Zola, please share your screen. We look forward to your presentation. Did you find my slide? Because I have some problem to share the screen.  I believe if you present with the slides as you shared with us, you can present in that format.  Did you see my screen? Yes, sir. Did you see? Yes, sir. We can see it. Okay.  I'm Paolo Zola, and I'm the Chair of the Gynecology and Oncology Unit at the University of Turin.  This is my disclosure.  With my co-authors, I would like to thank the scientific committee who allowed us to share with you the final data about the trial devoted to explore the management  of the follow-up in endometrial patients that treated cancer.  As you know, the endometrial cancer occur in less than 20% of the cases, and the majority arrive within three years from the initial treatment. And a lot of that are symptomatic.  In the early 20s, the available guidelines focusing on follow-up were contradictory. And the follow-up schemes adopted by center are very heterogeneous.  In reality, the follow-up involved a significant investment of clinical resources, and no randomized clinical trial was available to assess the best follow-up scheme to adopt.  For this reason, we decide to design this trial, a totem trial, in order to compare with a randomized trial an intensive versus minimalist regimen  five-year follow-up in endometrial cancer patients in terms of overall survival.  The trial design is very simple. We stratify patients in low risk and high risk, and then we randomize in intensive versus minimalistic regimen. While in the low risk,  the intensive was included  clinical examination every four months for five years, pap smear systematically every year, and CT scan in the first and the second year,  while the minimalistic received just a clinical examination.  In high risk patients, in the intensive, we perform systematically biomarkers, ultrasound, pap smear, and CT scan every year until the five years, while in the minimalistic regimen,  we perform just the clinical examination and two CT scans after the first and the second years from the treatment. The inclusion criteria are age more than 80 years,  endometrial cancer, all stages histological confirmant, and after surgery. No previous or concomitant second neoplasm, no hereditary syndrome, and seeing informant constant signs  at the moment of the randomization. The primary endpoint is overall survival, and the vital status of each patient was checked at the local registry for all Italian patients.  The secondary endpoint was relatively survival, quality of life, compliance of the follow-up program, and cost. We assume that intensive regimen could have induced an improvement  of five years overall survival from 75% to 80%, and for this, we need 2,300 patients. But after 10 years of the trial, an independent panel of experts decided to close the accrual  when we have enrolled 1,800 patients because we achieved sufficient power to afford the analysis, and so we performed the final analysis at that moment.  This is the accrual of the trial, and 39 Italian centers and three French centers were involved in 10 years. And this is the patient study flow,  and as you can see, we have already for the analysis 1,800 patients in 60% low risk and 40% in high risk, well balanced in the arm of the trial. This is the patient's feature.  As you can see, it's well balanced in the intensive and minimalistic arm. We have the same age, median age, and also the distribution in the risk factor  are well balanced in all the arm of the trial. As far as the treatment is concerned, more or less half of the patients, 50% more or less, was treated by laparoscopy,  and the majority received a total hysterectomy with bilateral salping of the rectum. The surgery alone was performing 66% of the patients,  while the remaining 34% received some adjuvant treatment in radiotherapy or chemo or both. The compliance was acceptable, 75% similar in the intensive and minimalistic arm,  and it's expected that the mean number of recorded exams  were markedly higher in intensive than in minimalistic arm. This is what we want to achieve. Some additional unplanned examinations were carried out in both arms.  And this is the result. As you can see, the overall survival is completely equal in the two curves, in minimalistic and intensive. This is the general overall survival,  but also if you look in low risk and in high risk, there is absolutely no difference between the two curves. There is no difference.  And also the same results we achieve in relaxed free survival.  The path of recurrence, the majority of the path of recurrence was distant, were in the 67%, and the remaining are spread with the pelvis and vaginal wall.  But what is very interesting, and that was the clinical examination alone, or with the in combination diagnosed  the vast majority of the relapse in low-risk patients, but more or less the same arrive  also in high-risk. And what is very interesting, the pap smear, the ultrasound and the biomarker  have no role in the diagnosis of the relapse. The majority of the relapse were treated with  by chemoradiation or chemotherapy alone, because the majority was distant metastasis.  And as far as the quality of life is concerned, there is no impact of the two regimens in the quality of life in low and high-risk patients, both in the physical component  and in the psychological component of the quality of life. So, just to summarise the results,  the item was, the strength was the last trial with the long follow-up representative of the  real-life population and the street verification of the life status in August 2020 in the world  cohort. And the analysis underlined that the high-intensity regimens have no impact in the overall survival. We know that we have the weakness because the stratification or risk  of recurrence do not take into account the lymphovascular space invasion, because at the  moment of the, when we start the trial, it is not so important. Only remote monitoring and so  can have some problem in perhaps that some relapse may be underestimated. The performance  of some additional exam could have reduced the difference between study arms. But we can conclude  that the intensive follow-up in dometrial cancer-treated patients do not improve overall  survival, even in high-risk patients. The quality of life in our study is not influenced by different  regimens of follow-up. According to our data, there is no need to routinely add vaginal cytology, laboratory or imaging investigation to the minimalist regimen used in this trial.  And we thank all the centers that made this trial possible and all the patients and their families who agreed to participate. Thank you for your attention.  Thank you, Dr. Zola. We're now going to hear from Flora Backus from the Ohio State University presenting a distillation of these two presentations. Flora?  All right. Thank you very much. I'm Flora Backus, gynecologic oncologist at the Ohio State University in Columbus, Ohio.  All right. Here are my disclosures.  So, the first, or actually, the secondly presented trial addresses the question of intensive  follow-up. It does this improve the overall survival in endometrial cancer. And they used  this very elegant design of patients treated for endometrial cancer, divided them in low-risk  and high-risk of recurrence, and then in an intensive or minimalist surveillance strategy.  They were able to identify that in the low-risk patients, clinical exam detected 20% of the  recurrences. But with the addition of imaging, there are still an additional 25% of recurrences  detected, whereas CT only detected 2% of the recurrences. This is different from the high-risk  patients, where the clinical exam detected only 7% of the recurrences, and clinical exam and imaging over half. And this makes some sense, because most of these recurrences would be  more distant, whereas in low-risk patients, recurrences are often more local regional.  CT and ultrasound only detected an additional 10%, and then in both groups, there was a non-significant  and in both groups, there was a non-specified group or non-specified detection of about 15%.  We then also see that the patterns of recurrence, again, the majority is distant recurrence. So,  two-thirds of the recurrences were distance, whereas about one-third was a combination of either vaginal, pelvis, or local regional recurrences. And interestingly, they show that  even with a more intensive approach and additional imaging and other exams, there was no  difference in time to detection of relapse. And more importantly, the overall survival was not  significantly different between these two groups, neither in the high-risk or the low-risk group,  with either of the strategies. So, in conclusion, frequent imaging and other testing did not result  in overall survival benefit, and that makes some sense because the majority of recurrences are  distant, multifocal, and peritoneal, and likely not curable. However, we do need to continue  surveillance to identify these salvageable local regional recurrences and isolated distant  recurrence that is amenable to surgical resection or stereotactic body radiation. And so, it would  challenge us, and especially the authors also, can we identify subgroups that have a higher chance  of isolated salvageable recurrences where we should adjust our surveillance methods or maybe still incorporate slightly more intensive screening. For the first time with this trial,  so we now have prospect of randomized data to support what we've been doing in our patients.  The results here are very consistent with what we already have been doing according to the NCCN  or SGO guidelines with regular exams and imaging just as clinically indicated or recurrences  suspected. Very important, though, it remains, especially for this low-risk group, that symptom  review, exam, and clinical suspicion need to be continued, and regular exams are detected  to detect these potential salvageable local regional recurrences. In the high-risk patients,  also, we see here that the schedules that we've been using, both, again, with NCCN and SGO, are very similar to the minimalist approach used here. However, there is still some role,  potentially, for imaging as they did in this study. Finally, though, we can get rid of CA125 ultrasounds and pap testing, and it now has shown that this is not of any benefit  in any of these populations and should result in some cost-bearing. But I do want to  alert you to some caution as we minimize this surveillance and update our guidelines. Insurance uses our guidelines to determine insurance coverage for imaging, and imagine  this patient on, for example, a clinical trial for high-risk endometrial cancer, and we're trying to  set a new standard. Treatment A is compared to treatment B. In a surveillance or maintenance  period, we would like to continue to do imaging to see which patient has a recurrence or no  recurrence and which treatment is going to be the winner. Insurance will argue with us that if we  don't write our guidelines properly, that imaging an asymptomatic patient is not clinically indicated,  and they'll quote the NCCN guidelines. But I would argue that, in this case, imaging to monitor  response to treatment should be covered to insurance, and we need to be smart in how we relay this message about minimalizing surveillance in our guidelines as well.  The second presentation is understanding the implications of positive sentinel lymph nodes  in endometrial cancer, and their objective for this study was to identify clinical pathologic  characteristics associated with non-sentinel lymph node metastasis and non-vaginal recurrence in patients with sentinel lymph node positive endometrial cancer.  In this retrospective study of 103 patients with positive sentinel lymph nodes, 36 had ITCs,  27 micrometastases, and 40 macrometastases, and they identified in their multivariate analysis  that the predictors of recurrence were not so much just any lymph node metastasis, but particularly macrometastases, non-endometrioid histology, and cervical stromal invasion.  They also confirmed that the risk of positive non-sentinel lymph node increases with the size  of sentinel lymph node metastasis, and we've seen this in a couple other studies. But here in a  current study in the 38 patients with pelvic lymph node dissection, we see that if you only have  isolated tumor cells in the sentinel lymph nodes, there's a very low risk of non-positive endometrial  cells in the sentinel lymph nodes, whereas if you have micro or macrometastasis, this risk is  much higher. And that begs another question. What is the risk of retroperitoneal recurrences in the  era of sentinel lymph node mapping only? In GEOG258, we saw that the nodal recurrence was  higher in patients who received chemotherapy only versus chemotherapy followed by or as well as  external beam radiation. And so my questions for the authors is, was there a difference in recurrence patterns for patients with macrometastasis versus micrometastasis or ITCs?  And if so, how would you tailor adjuvant therapy for these patients with macrometastasis and extracapsular involvement in the area of sentinel lymph node biopsies only?  Thank you.  Thanks, Flora. That was excellent distillation of those abstracts. Next, we're going to have an abstract by Dr. Kogan, who will be presenting his pre-recorded abstract.  Hello, my name is Liron Kogan. I am from Adassa Medical Center in Jerusalem, Israel, and my topic is minimally invasive surgery in advanced endometrial carcinoma is associated  with increased risk for local recurrence. I have no disclosures.  Our objectives in this study were to compare oncological long-term outcomes of patients diagnosed with advanced stage endometrial carcinoma  operated by minimally invasive surgery versus open surgery.  This is a retrospective study from 11 Israeli hospitals. The patients in the cohort were  diagnosed and treated between 1994 and 2017. We included patients with advanced stage disease and excluded stage 4 disease. Our MIST group included many laparoscopies, about 80%.  We compared demographic, clinical, pathological, and survival data between the groups.  The cohort included 304 patients that were diagnosed, surgically staged, and followed  for a median time of about 52 months. Out of them, about a third were staged by MIST, 104 patients.  Patients that were operated by MIST were younger, with a median age of 67 versus 70,  probably healthier with less diabetes and hypertension, with lower CA125.  The laparotomy cohort patients were diagnosed with higher stage and grade. Here we can see recurrence Kaplan-Meier curve. No difference were found between the two groups,  not shown here, but same results were for overall survival.  When we looked at risk factors for recurrence as age, wait time for surgery, stage, grade,  and the number of patients that were diagnosed, we found that the recurrence curve was higher than in the MIST cohort. In terms of age, wait time for surgery, stage, grade,  lymphovascular space invasion, and mode of surgery, MIST versus open surgery, none of the factors was found to be significant in multivariable analysis.  Same for all-cause mortality. None of the factors was found to be significant in multivariable  analysis. However, when we looked on risk factors for local recurrence as vaginal cuff and pelvic  recurrence, minimally invasive surgery was found to be the only factor associated with local  recurrence in multivariable analysis, doubling the risk for recurrence, as you can see at the bottom.  Our conclusions were that MIST was associated with an increased risk for local recurrence compared to laparotomy in patients with advanced stage endometriosis cancer.  Further studies and clinical efforts should be focused on minimizing the risk for tumor dissemination in minimally invasive surgery.  I would like to acknowledge my team,  11 centers in Israel.  Thank you very much.  Thanks for that presentation. Next, we're going to hear from Dr. Bianca Renientzis.  Please begin your presentation.  So, welcome, everyone. I am Bianca Renientzis, and I'm pleased to present to you the follow-up  data of the Dutch TLH-TIH study entitled Recurrence and Survival after Laparoscopy versus Laparotomy in Early Endometrial Cancer, the Long-Term Outcomes of the TILH-TIH Study.  This study is based on the findings of the Dutch TILH-TIH Study, and it is based on the findings of the Dutch TILH-TIH Study entitled Recurrence and Survival  the Long-Term Outcomes of a Randomized Trial. I have nothing to disclose.  As you might all know, is endometrial cancer one of the most common gynecologic malignancies worldwide, and it accounts for around 380,000 women who are newly diagnosed every year.  For the Netherlands, it's around 2,000 women who are diagnosed annually. And this incidence is steadily increasing due to an increased prevalence of risk factors,  such as obesity and aging. But luckily, over 80% of women are diagnosed when they're still in early-stage disease. And this is because postmenopausal blood loss is one of the  presenting symptoms of early-stage endometrial cancer. And treatment is surgical removal to  uterus with a bilateral sublingual ophorectomy with or without a pelvic and para-aorta lymph node  dissection. Traditionally, this was done by laparotomy via vertical midline adhesion.  But since the introduction of minimal invasive surgery, laparoscopy has become the standard  treatment for early-stage endometrial cancer. It is less invasive, and it is associated with a lower mobility. So far, there have been multiple multi-center randomized control  trials who have shown the surgical safety of the laparoscopy in comparison to the laparotomy.  They have shown that there are equal major complication rates, but an improvement in the  short-term outcomes, such as less blood loss and less pain after the laparoscopy. Furthermore,  there have been two large randomized control trials who have published their long-term survival data. This is the Australian LACE trial and the LAB2 trial in the United States.  Both these studies showed that after a follow-up of around three and a half to four and a half years, the overall and disease-free survival rates were comparable between groups.  However, in both these trials, lymphadenectomy was part of the routine treatment, even in early-stage disease. According to the ASTEC study group, lymphadenectomy does not improve  the overall survival for early-stage endometrial cancer, but it might increase the risk of  complications during surgery. And therefore, we do not perform a lymphadenectomy in Europe as  standard procedure for the early-stage endometrial cancer. And that is the reason why we conducted  this follow-up study. The initial study was the Dutch randomized control trial who compared the  laparoscopy to the laparotomy for women with early-stage endometrial cancer, in which a  lymph node dissection was not part of the routine treatment. Women were included between February  2007 and January 2009 on a two-to-one randomization basis in favor of laparoscopy. And in total,  there were 279 women included in the study in 19 teaching and non-teaching hospitals in the  Netherlands. The primary outcome parameter was a major complication rate as indicator for the treatment-related mobility. And this study found comparable major complication rates.  Secondary outcome parameters were minor complications, quality of life, and cost-effectiveness,  and this study found that there was an improvement in the minor complications after the laparoscopy.  There was less blood loss, less pain, shorter hospital stay, and a quicker resumption to daily activities, as well as an improved quality of life up to three months post-operative,  and the laparoscopy was cost-effective. For the follow-up study, we included all the 279 women in the 19 teaching and non-teaching  hospitals in the Netherlands, and as part of the initial study, they all gave a written informed  consent to perform a follow-up up to five years post-surgery. Now, primary outcome parameter is  disease-free survival, with the secondary outcome parameters being overall and disease-specific  survival, as well as primary site of recurrence. Well, in this slide, you can see the patient  characteristics of the initial study group and the follow-up group, and what I would like to  show you is that the patient characteristics of the follow-up is comparable to the initial study  group, and in total, we included 94% of all the women, 263 women in total, and also the patient characteristics of the laparoscopy were comparable to the laparoscopy.  Then, the follow-up data. The median time of follow-up in our study was around five years,  and in total, there were 29 women who developed a recurrence, 16, around 10% in the laparoscopy  group, versus 13, around 16% in the laparoscopy group. In neither group, port sight or wound  metastasis developed, and in both groups, there were two women who developed only vagina-fold  disease, and in addition to this, there was one woman in the laparoscopy group versus four women  in the laparoscopy group who developed concurrent vagina-fold disease, with a median time to recurrence of one and a half years. Then, our primary outcome parameter,  disease-free survival. As you can see in the figure on the right, after a follow-up of five years, the disease-free survival rate in the laparoscopy group was around 90%, and in the  laparotomy group, it was around 84%, with a log-rank P of 0.19. We also looked at the effect of surgical techniques by performing a multivariable tox regression analysis,  in which we adjusted the hazard ratios for well-known prognostic factors for endometrial  cancer recurrence. Age, figure stage, and then the higher stages, two to four, compared to stage one, and rate of differentiation, high rate versus low rate, and as you can see,  no statistically significant difference was found for endometrial cancer recurrence.  For the secondary outcome parameter, we looked at overall survival, and in total, there were 38 women who died during the follow-up,  19 in both treatment groups, and after five years of follow-up, the overall survival rate in the laparoscopy group was 89%, and in the laparotomy group, it was 83%,  with a log-rank P of 0.06. Also, for the overall mortality, we looked at the measure of surgical technique, and again, we adjusted the hazard ratios for the same prognostic factors,  and also for the overall mortality, we did not find a statistically significant difference.  At last, we looked at the disease-specific survival, and for this, there were 80 women  who died at the end of the five-year follow-up due to the causes of endometrial cancer recurrence,  nine in both treatment arms, which gives a disease-specific survival in the laparoscopy group of around 95%, and in the laparotomy group, around 90%, with a log-rank P of 0.17.  Also, for the disease-specific mortality, we looked at the surgical technique, in which we  adjusted the hazard ratios for the same prognostic factors, and also for the disease-specific  mortality, we did not find a statistically significant difference. They were comparable.  Which brings me to the conclusion, and that is that this is the first multi-center randomized  control trial that compared the laparoscopy versus laparotomy in early endometrial cancer, in which routine lymph node detection was not part of the surgical treatment.  The analysis we performed showed comparable disease-free overall and disease-specific survival rates, as well as comparable primary site of recurrence between the laparoscopy  and the laparotomy, after five years of follow-up. And this supports the widespread use of the laparoscopy as primary treatment for patients with early endometrial cancer.  This study, I performed together with Mieke van Zuylichem and supervised by Professor Marjan  Maurits and Professor Gerrit Geijder de Bock. And furthermore, I would like to thank all the  different hospitals in which we could perform the initial and the follow-up study. So, thank you, and thank you all for listening.  Thank you, Dr. Rentschies. Very interesting presentation. I now invite Dr. Mario Leteo from the Memorial Sloan Kettering Cancer Center to present his distillation on these two  presentations. Dr. Leteo.  Thank you, Dr. Miller, and thank you for inviting me to be able to have the privilege of doing the  distillation for these two outstanding and very interesting abstracts. Hopefully, I can put this  in the context of our current knowledge of minimally invasive surgery and endometrial cancer, as well as provide some questions and commentary for the authors' consideration as  they continue to put these data together and submit for revocation. These are my disclosures.  So, as background, just to remind everyone, I think these are very well-known studies, but GLG Lab 2 was a randomized trial assessing laparoscopy versus laparotomy for women with  endometrial cancer. These were all clinically early stage. Of course, at the end, there were  some stage 2, 3, and 4 cases, but this study enrolled 2,600 women, and the cumulative incidence  of recurrence was the same between both arms. This is currently the largest randomized trial  in this disease for a surgical approach. The overall survival, there are two curves here,  but they are superimposed. Again, laparoscopy results in similar outcomes to laparotomy,  based on this large randomized trial done by the GLG. The LACE trial, which was out in Australia,  basically confirmed these findings, and in both recurrence and survival,  laparoscopy was not inferior and was actually said to be equivalent to open surgery in both terms of recurrence and overall survival. And this study was also randomized, but again,  had slightly less patients randomized with about 800 women randomized in this study. Again, these are two of the largest randomized trials to date in this cohort of women,  which basically led to the statement that MIS is standard approach for women with newly diagnosed,  clinically confined to the uterus, endometrial cancer. And why do we do MIS? Well, because,  at least in endometrial cancer, this is using a large dataset from the American College of  Surgeons NISQIP data, that the more you increase the rate of MIS in this disease, in these cohort  of patients, you have a direct correlation with a decrease in the number of complications, as well  as the number of hospital stays. This absolutely leads to improved patient outcomes, as well as  decreased costs to the healthcare society and system. Dr. Kogan today showed us the work of  him and his other co-investigators assessing minimally invasive surgery and advanced endometrial  carcinoma. And the title is that it was associated with increased risk for local recurrence.  I think it's important that we always continuously assess our outcomes and individual outcomes also,  despite randomized trial. This was a multi-center retrospective cohort study. It was 11 centers in  Israel from the time period of 1994 to 2017, and it included stages two to three C. So just a few  little comments on this design. This was a long time period of 24 years. I don't know when these  investigators started doing laparoscopy, but obviously this would introduce a potential learning curve concern in this dataset. These were 304 cases over 24 years among 11 centers,  and I'll do something unfair to him and say that this results in, by simple math, 1.2 cases per  center per year. Now, of course, that's not fair, but we were unable to see what the actual  distribution of the cases were over centers over a time period. But again, this starts to introduce  a little bit of concern over the dataset being such a long time period with relatively small  numbers. And stage two, is stage two truly considered advanced? It would have been interesting  to see the difference between the stage two versus the stage three cases in their outcomes.  Also, how many of these stage two were detected preoperatively? It'd be of interest to know that.  Would you alter your approach if you knew preoperatively that there was cervical involvement? And how many of the stage three also had cervical involvement? I think that'd be an  important thing to know, and I'm sure he has these data, and hopefully he can consider these as he  moves forward with his study. These are the baseline demographics of his two cohorts,  or 200 open cases and 104 million invasive cases. I mentioned that eight that were younger in MIS, diabetics, were less in the MIS group. CA125, I'm not quite certain. I mean,  it was a lower number, but we don't use this routinely clinically in the U.S. for endometrial  cancer, so I'm not sure this would be applicable to most patients. He did highlight that there  were more stage three cases, but at the same time, I would highlight that there were more stage two  in the MIS group, suggesting there was more cervical involvement in those who had MIS surgery. Could this be a potential reason for their ultimate findings? It would be interesting  to see what the histologic distribution was between the cohorts. I'm not sure if that would  have a huge impact, but it would be interesting to see this. And again, as I mentioned, over a  24-year period in Orlando Centers, with having younger patients with less diabetes, does this  reflect an adoption curve as well as a learning curve effect on these data? The main point,  actually, is that there was no difference in recurrence in overall survival, and I personally  would have left that as the title of the abstract, that there really was no difference in recurrence,  resurvival, overall survival, as mentioned. It was highlighted that when they looked at local  recurrence, defined as vaginal cuff or pelvis, that there was an increase in local recurrence in patients with minimally invasive surgery, and this was based on adjusted analysis.  Now again, questions come, were these mostly in cases of cervical involvement, and does that really matter? How many were isolated local recurrences, meaning, you know,  how many of these had vaginal and pelvis, but also had distant metastases? And ultimately, clinically, does it matter if this is true, if the overall recurrence rates are the same  between the two groups anyhow? Just in GOG Lab 2, this is the forest plot from subgroup  analyses, looking at various factors and trying to assess if there's a group where laparoscopy  may be worse or better, and here they had 389 stage 2 to 3 C cases, and there was no recurrence  difference between laparoscopy and laparotomy in GOG Lab 2 in a subgroup analysis of the stage 2 to 3 C cases. If you look at the sites of recurrence in GOG Lab 2, the rate of local  recurrence was exceedingly low between both MIS and OPEN, with a 2.9% rate in MIS and a 2.5 rate  in OPEN. Of course, local recurrence specifically to stage 2 and 3 C was not reported in GOG Lab 2,  so I cannot make those comparisons. LACE trial also had 124 cases of the same stages, and they had a very low local recurrence rate also. And an NCDB study looking at stage 2  endometrial cancer specifically, which is cervical involvement, showed that there was actually no  detriment to MIS in this stage 2 endometrial carcinomas, and actually in univariate analysis,  there was a trend towards better outcomes in MIS. Dr. Rentjens presented their follow-up data from  the randomized trial, the Dutch randomized trial, which you are also familiar with, endometrial cancer. This, again, as a reminder, was a randomized trial of laparoscopy  hysterectomy versus OPEN hysterectomy alone without lymphadenectomy. It is important to remember that the primary outcome and design of the study was to assess the treatment-related  morbidity, not oncologic outcomes. It was designed with an 80% power to detect a 15% difference in major complications. The current analyses presented of long-term follow-up for  oncologic outcomes represents most likely a post-hoc or ancillary or yet another secondary  outcome. The primary outcome, to refresh everyone's memory, was the major complication rate  was actually not different between laparoscopy and OPEN hysterectomy. The minor complications  was also no different. What was different was that in those that had laparoscopy, there was much  less blood loss, a shorter hospital stay, as well as the use of pain medications was less than laparoscopy. They also subsequently published that the quality of life was improved  in those with laparoscopy, as well as it was more cost-effective to do laparoscopic surgery.  This is the follow-up, the results, and again, the final message is that there was no difference  in oncologic outcomes and either disease-free overall or disease-specific survival between the  laparoscopy and an OPEN approach. So again, there was no statistical difference in these,  but there may be an issue with the small numbers and this not being designed primarily to answer  an oncologic outcome. I put power in quotations because for this, if you actually look at this,  and if this was a different disease and these curves are flipped, we'd be all up in arms, but MIS is actually the top curve here, the blue line, and the hazard ratio is 0.76,  which is actually in favor of MIS in terms of an oncologic outcome. So I would actually argue,  and if responding to reviewers when she submits this, say that it was actually, may not have been powered, quote-unquote, to detect the potential benefit of minimally  invasive surgery statistically. So just something to consider here. And again, I congratulate  both all Drs. Kogan, Dr. Rentjens, their co-investigators, and of course, the many patients  who allow us to do these things on them. MIS continues to be the standard surgical approach in patients with newly diagnosed endometrial cancer with all histologies and stages,  and I think these two abstracts actually confirm that. If there is a local recurrence problem,  it does not translate or did not seem to translate to an overall recurrence issue in these cohorts,  nor survival issues. The role of lymphadenectomy or central node mapping cannot be addressed with these two abstracts. And again, remember, surgery is not a drug-delivered equine. I  congratulate these authors and Dr. Kogan and Dr. Rentjens, and I encourage all surgeons to always  objectively assess their own outcomes despite randomized data being published. Thank you all  very much. Thank you, Dr. Latteo, for that very astute distillation. I think we have about a  minute or so for questions. I'll turn that over to Dr. Kreuzberg. Thank you so much, David. I  think there was one question of the audience, and it was for Dr. Zola. Yes, it's here. Yeah.  The question from the audience was, how often were the recurrences discovered at the moment  of scheduled appointment with scheduled scans or in between scheduled appointment and with  scans done by symptoms? In reality, the so-called interval recurrence between the two scheduled  control are very rare, less than 20 percent. The majority are diagnostic during the clinical  control. And consider also that the vast majority of the recurrence, at least in the low-risk patients, are asymptomatic. So it is very interesting that we can find a lot of these  recurrences during the control, and the interval recurrence are very rare. Also in the high-risk  group? Yes, the same arrive in the high-risk group. So in these cases, we perform systematically CT scan every first and second year. So the association between clinical control and  CT scan improve a little bit the capability of diagnosis of the procedure. But also in these  cases, the interval recurrence are very rare, less than 20 percent. Okay. Thank you so much, Dr. Zola.  And thank you, Dr. Kreutzberg. This concludes Plenary 2. Up next in this hall will be a postgraduate educational course, Rare Tumors Including GTN. Hall 2 will feature a surgical  debate on Hypec. And Hall 3 will be another postgraduate course from poster to plenary in 60 minutes. These courses will start shortly. A reminder that all the sessions  will be available on demand through December 4th. We thank you for your attention.  Okay. Bye-bye. I got you. Bye. Thank you. Thank you all. Bye-bye. Thank you all.

Video Summary

Thank you.