Hi there, my name is Jubilee Brown. I'm the professor and division director of gynecologic oncology at Levine Cancer Institute at Atrium Health in Charlotte, North Carolina in the United States. Thank you so much for tuning in and allowing me to share some thoughts with you on minimally invasive surgery in ovarian cancer. These are my disclosures. Today we'll describe the published literature surrounding neoadjuvant chemotherapy and interval debulking surgery. We'll see some techniques regarding minimally invasive surgery for interval debulking, and we'll talk about clinical recommendations regarding surgical options for patients with advanced ovarian cancer. Traditionally, and in most settings, ovarian cancer has been treated with laparotomy, with a total abdominal hysterectomy, bilateral salpingo oophorectomy, and staging or tumor reductive surgery. This is typically followed by six cycles of taxane and platinum-based chemotherapy, and then followed with surveillance. Recurrences are treated with chemotherapy. However, there is a change in the landscape of the opportunities that we have in treating patients with ovarian cancer. In fact, in all gynecologic cancers, we're transitioning to less open surgery and more minimally invasive surgery. Specifically with relation to ovarian cancer, we are able to incorporate minimally invasive surgery into multiple areas of management, and specifically, the increasing use of neoadjuvant chemotherapy allows for more, sorry, for less morbid surgery and more minimally invasive surgery. So, we'll talk about all of these details today. First, let's consider the role of minimally invasive surgery in ovarian cancer. As I see it, there are five areas where minimally invasive surgery plays a role in ovarian cancer, and these include diagnosis, primary surgery and staging in early stage disease, evaluation of advanced stage disease at the time of initial diagnosis, and in fact, this allows accurate diagnosis and assessment of an R0 or complete resection. The fourth way that I think minimally invasive surgery can be utilized in ovarian cancer is at the time of interval cytoreduction following neoadjuvant chemotherapy in advanced stage disease, and lastly, the resection of isolated recurrent disease. Today, we'll focus on the evaluation of advanced stage disease at the time of initial diagnosis and the use of interval cytoreduction following neoadjuvant chemotherapy in advanced stage disease. Let's first talk about the assessment of an R0 resection. Anna Fagotti published, and I'm trying to get my video to play, there we go. Anna Fagotti published on the utility of laparoscopic evaluation for the ability to perform an R0 resection. In other words, can our findings at the time of laparoscopy determine whether we can achieve an R0 resection at that time? And she includes six components in her scoring system. Patients are scored with either a zero or a two for involvement of carcinomatosis, diaphragmatic involvement, mesenteric involvement, omental involvement, stomach involvement, and parenchymal liver metastasis. As you can see, as you can see, we can really see very well with minimally invasive surgery. And what we know is that we can score these patients and patients who have over a score of eight, in other words, if they score positive for four of these areas where there is disease, we will be unable to achieve an R0 resection and instead should proceed with neoadjuvant chemotherapy. This leads us to a triage strategy where we take this so-called Fagotti score. Patients who have a score of zero to eight undergo a primary debulking surgery followed by six cycles of chemotherapy with or without Bevacizumab followed in some cases by a PARP inhibitor. Patients who have a score over eight, we know we are not going to be able to achieve an R0 cytoreductive surgery. So instead we treat these patients with neoadjuvant chemotherapy for three to four cycles, and then we come back for an interval cytoreduction. And we'll talk about this. This may or may not include minimally invasive surgery, again, followed by three more cycles of chemotherapy with or without Bevacizumab and sometimes followed by a PARP inhibitor. But the key here is utilizing laparoscopic survey to determine the Fagotti score that tells us if we should do a primary debulking or if we should give neoadjuvant chemotherapy and proceed with interval cytoreduction. So let's talk further about that second approach. Let's say we take a patient and we see that her Fagotti score is over eight and we proceed with this latter approach. Well, here's an actual patient that had this happen. So this is my patient who's a 66-year-old female who presented with bloating, cramping, hematochezia, weight loss, and four months of early satiety. Her colonoscopy showed an obstructive lesion that was non-diagnostic. Her CA125 was 98 and her CEA was 1.2. We can see that at the time of her surgery, we did a laparoscopic unilateral salpingo-oophorectomy and biopsy of tumor. This was a high-grade serous carcinoma. And you can see based on the level of disease here, that's tattooing from the colonoscopy, that a colostomy would have been required to remove all this. So instead, we obtained the diagnosis and we did a colonoscopy. To remove all this. So instead we obtained the diagnosis, we performed a laparoscopic USO, and then we came back after three to four cycles of chemotherapy. She had had some response and we were able to completely resect her disease. Laparoscopically, we were able to remove the residual tumor. She'd had such an excellent response after three to four cycles. I think she had four cycles of chemotherapy. You can see we're able to do a complete omentectomy this way without any injury to the colon. And using a hand port, we're able to do now a bowel resection to remove this residual area. It's much, much smaller. It's off the wall, off the pelvic sidewall. And we can perform a stapled resection and anastomosis using just that hand port. So this is just a sort of a clinical example of how we can utilize laparoscopy first for evaluation and then treat with chemotherapy for neoadjuvant chemotherapy. We can come back, avoid the colostomy, and achieve, as you can see, an R0 resection. This patient had an excellent response. Her CA125 declined to 13. You can see we did a laparoscopic interval, total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, radical tumor resection, R0 debulking. She did not require colostomy. We did, of course, center for genetic testing and her germline testing showed a pathogenic mutation in BRCA2, which may account for the excellent response that she had. Now, we have, in fact, four randomized prospective trials about neoadjuvant chemotherapy. Now, all are in the open setting. But we know now, based on these four trials, that neoadjuvant chemotherapy is a reasonable approach. So when we compare, in these four trials, primary debulking surgery with neoadjuvant chemotherapy and an open interval debulking, what we see in every study is that there is an equivalent or greater rate of achieving optimal tumor reduction. And we can see that the progression-free and overall survival are no different. And in fact, we can see a lower complication rate, a lower rate of permanent colostomy, and a lower rate of postoperative complication requiring surgery. In addition, we know the benefits from minimally invasive surgery. Not only is there cosmesis, and here's a patient of mine who underwent the surgery, as you can see, three small little five-millimeter ports, but we also know that there's less blood loss, shorter hospital stay, decreased rate of complication. We know from several retrospective studies that there's a reduced rate of unnecessary laparotomy. Multiple studies have now shown that MIS for interval debulking is safe and feasible with better perioperative outcomes and up to 100% R0 resections with less than 5% intraoperative complications, and less than 2% severe complications. So we actually looked at our own data and published these data a couple of years ago. What we found was that in this selected patient, and keep in mind, we selected our patients. These were not randomized. This was a retrospective analysis where patients received either laparotomy or minimally invasive surgery for their interval cytoreduction. Over 95% of patients were able to achieve optimal cytoreduction, and that was true for both minimally invasive and laparotomy group. In fact, 10% of patients had a complete pathologic response to neoadjuvant chemotherapy, true whether it was performed with laparoscopy, and minimally invasive surgery was completed without conversion to laparotomy in 83% of patients. This did require a hand port or a mini-laparotomy in about half of patients, but that doesn't affect their overall recovery time. I think very important is to see in our data there was no difference in progression-free or overall survival in these two groups of patients. This is wonderful Lane Drury, who presented our data. We updated this information in a multi-institutional review with both the University of North Carolina and my home institution, Atrium, in 254 patients, and we included robotic patients in this. 84% of patients were able to achieve their surgery without conversion, and in fact, the conversion rate was equivalent in both laparoscopic and robotic arms. As you might expect, minimally invasive surgery showed a lower operative time. I'm sorry, open surgery showed a lower operative time, but minimally invasive surgery showed a lower blood loss and a shorter hospital stay, in fact, with a decreased rate of 30-day complications and readmission. Again, there was absolutely no difference in outcomes, and so we published this information as well. All of these retrospective data have led to the LANCE trial, which is a prospective international multi-center randomized non-inferiority trial. There's a feasibility lead-in that will lead to a phase 3 trial, including 549 patients estimated. The primary endpoint is non-inferiority of disease-free survival. So in summary, I think we can see there are multiple ways that we can use minimally invasive surgery in ovarian cancer, and of course, the details continue to be studied, but these are the most updated data that are present. The role includes diagnosis, primary surgery and staging in early stage disease, evaluation of advanced stage disease at initial diagnosis with the Fugati score to allow assessment of R0 resection, utilizing this in good responder patients to achieve an interval cytoreduction after neoadjuvant chemotherapy and advanced stage disease, and not discussed today, resection of isolated recurrent disease. This, in summary, appears to be safe, feasible, evidence-based, and is currently undergoing prospective study. Thank you so much for the opportunity to present today, and I just need to shout out to my wonderful team of teams here at Atrium Health. So thank you very much, and I appreciate your attention. Have a great day.

minimally invasive surgery

ovarian cancer

neoadjuvant chemotherapy

diagnosis

primary surgery