secondary surgery for recurrence of ovarian cancer, but in order to answer this question, I thought I'd start a little bit before that and maybe just sort of think about the question about does any surgery for ovarian cancer add survival benefits? Sometimes when we speak to our medical oncology colleagues, they sort of give us the impression that the only answer for epithelial ovarian cancer is chemotherapy. So as a surgeon, I wanted to make this point a little bit to sort of say, why do we do surgery in the first instance? And I think just a few basic principles, the theoretical arguments for primary debulking surgery include removing large necrotic tumors in order for the chemotherapy to work better. So we have evidence to suggest that smaller tumors with a higher growth fraction would be more chemosensitive. And by removing a big tumor, we often improve the clinical functioning of our patients by improving nutrition and their immunological status. So we're all aware of this sort of golden target of trying to get as little residual disease as possible after site reduction, and that sort of controlled our thinking for many years now. Just one example of studies that showed that getting optimal site reduction makes a difference. You can see on this survival curves on the Kaplan-Meyers that if we can get disease down to sort of no visible disease, we do have a much better progression-free survival and overall survival compared to patients where we don't achieve optimal site reduction. You can see there's a dramatic difference between no visible disease, even one centimeter of disease, and then more bulky disease. So as surgeons, we've always been trained that this should be our target to get optimal site reduction, but that often comes at a cost. And we should think carefully before we just rush in and do surgery and operate, because we can often make significant sort of morbidity and even mortality by doing injudicious surgery. And decision-making around surgery, the timing of surgery, is often the weakest link in our multidisciplinary teams. And the decision to do surgery is often left to junior and inexperienced clinicians. So my plea is that if we do consider surgery, discuss it in a multidisciplinary team. So this is an important study, I think, for the fellows just to take note of, the Maria van der Burgh classic study about operating a second time when you've had incomplete site reduction with your first procedure. And this group clearly showed that if you do three cycles of chemotherapy in somebody that was considered incompletely operated for the first attempt, if you give them a second attempt at surgery, they had an improved survival. So this already sort of gave us the indication that surgery is important, and it makes a difference in terms of patient outcomes. And this led to, you're very well aware of the studies done on neoadjuvant chemotherapy versus primary surgery, and the fact that certain people explored this concept of starting somebody with primary chemotherapy followed by interval primary surgery after maybe three cycles of chemotherapy. And that led to better rates of optimal site reduction, because you can imagine if we downstage the tumours with chemotherapy, we will also get better chances for site reduction, and also less perioperative morbidity and even mortality, less ICU admissions, and in places where I work, and I guess where you work, intensive care facilities are a scarce commodity, and it's often difficult to get a patient into an ICU environment post-operatively. So we need to use those resources properly. So the evidence for the EORTC study is based on a randomized study design where almost 700 women with advanced ovarian cancer was examined for two clinical management strategies. In one group, the patients received primary surgery followed by chemotherapy, while in the other group, they had neoadjuvant chemotherapy with three cycles of platinum-based chemo followed by surgery with three further cycles of chemotherapy afterwards. And if you look at the two different groups, the neoadjuvant chemotherapy group versus the primary debulking surgery group, one of the most striking differences in outcome was that in the neoadjuvant chemotherapy group, there was a much better rate of primary debulking or complete site reduction, and also getting it down to minimal disease was much better in the neoadjuvant chemotherapy group. And it's important to note that the rates of severe hemorrhage was much lower in the neoadjuvant chemotherapy group compared to the primary surgery group. And you can see this, in my opinion, actually unacceptable perioperative death rate of 2.5% in the primary debulking surgery group. So again, if we decide to do surgery, our first priority must be to do no harm, to do good. So the outcome of the survival curves shows us that the curves for the primary debulking surgery and for the neoadjuvant chemotherapy groups are very similar, with no negative impact on survival. And this was repeated in other studies as well. The other famous study in this regard is the CORUS trial, and you can again see the differences in outcome in terms of perioperative death in the primary debulking surgery group versus the neoadjuvant chemotherapy group is striking. So we need to ask ourselves, why don't we do neoadjuvant chemotherapy more often? These are the survival curves for the CORUS trial, and you can see almost exactly the same. In Cape Town, we have two academic tertiary level hospitals that do gynecology surgery, and we have a joint protocol that we bring out every few years. And in 2015, we, as two sister institutions, decided that we will offer neoadjuvant chemotherapy to everybody with presumed epithelial ovarian cancer with large volumes of ascites or perilefusions. We'll use neoadjuvant chemotherapy for elderly and frail patients, and when there's no ICU available, we often have long surgery waiting times, so also in that scenario, neoadjuvant chemotherapy is preferred. But we do acknowledge that in many instances, primary debulking is still the preferred option. So we don't want to make a complete rule for every single person. So now to get back to my original question, you remember we asked, does secondary surgery for recurrence add survival benefit? And I think this is, again, for the fellows, a very important landmark study that was published in the New England Journal of Medicine only in December last year, where the German oncology group, the randomized trial of surgery versus no surgery for first recurrence. So they looked at a specific group of patients with a sort of good performance status, so they sort of used the AGO score. In the past publications, the desktop OBAR criteria, if you remember those publications, but the AGO score basically identified a subgroup of people with good performance status, complete resection at the first surgery, and a low volume of ascites at first recurrence. So then that group of people that offered either just chemotherapy or chemotherapy with surgery, and the study was sort of aiming to try and figure out whether surgery plus chemotherapy was better than chemotherapy alone. Remember, this is only now looking at first relapse, and there must be imaging to support the relapse. You can't just have a biochemical CA125 type of diagnosis of relapse. Multi-center study in multiple countries, and you can see these patients had a fairly long platinum-free period. In other words, their recurrences happened only after 18 to 21 months later. And they could, or maybe just saying a little bit about the demographics of the two different groups. So in both groups, the surgery group and the no surgery group, they worked mostly with advanced stage epithelial ovarian cancer, and as expected, the majority of these women had high-grade serous tumors. So if we look at the survival curves, you can see there's definitely a difference between the cytoreductive surgery arm and the no surgery arm in favor of those women that had a second surgical procedure. And this supports the same progression of the survival. So this supports a second procedure for a selected group of women for their first recurrence. And I think now we have got evidence to say this is actually a reasonable approach, and it's something that we should offer our patients when they have a long disease-free period after they've completed their initial chemotherapy, and we can give them a little bit of evidence about the expected benefit. So my final slide is really about thinking before you just do the surgical procedure for ovarian cancer, to think carefully, to speak to your multidisciplinary team colleagues. And that's really the key to success, is if we work together, we will have better outcomes for our patients. Okay, so that is my didactic for this afternoon. I know I've rushed a little bit through this, but I'm...

surgeon

surgery

ovarian cancer

neoadjuvant chemotherapy

recurrence