Great, well thank you IGCS and everyone and I just thought that we had a case of ovarian cancer so we're going to talk about the quality indicators and training for cytoreductive surgery and this experience is based on my training and my work experience both in UK and India and this talk is not conflicted. So great, so the key messages for today I'm going to talk a little bit about the evidence, about the training, quality indicators and assurance because it is a high risk procedure and it needs a dedicated service and then combining all of the above for a practice based on evidence or generating evidence when it requires further research and not based on convenience and you know all the convenience factors I don't need to go through them. So why is it important? Because I think it's going to be the next woman cancer pandemic definitely for low middle income countries and an expected rise of 50 percent in the next 20 years. In India it is underreported, increasing numbers seen in the clinic every day is the costliest woman's cancer to treat and our women are considerably younger. So compared to before where it used to be a disease of palliation with survival, low survival, now people can live much longer even up to 120 months. So it's the paradigm shift from palliation to cure but it bases on a post-code lottery and three things which have contributed to this increased survival is the BRCA, HRD, PARP inhibitors and surgery and I'm fortunate enough to be involved in the discovery or the process in all three. So 10 years down the line I still think that a good biology does not compensate for a poor quality surgery. Improved quality reduces the cost in the long run so four hours extra in theatre, four days extra in ICU does provide four years of extra life and this is a duty of candor to tell to the patient and surgery is the most cost-effective cancer intervention for advanced country advanced cancer in low resource country setups especially when you don't have targeted therapies but it does need a dedicated team like transplant surgery you will not do in the primary setup. So indications primary whether it's primary or NSTT it's a mainstay when the patient is fit and is resexable there are guidelines and indicators which I'm going to talk about it but just to to reiterate the fact that these guidelines are for abdominal clearance irrespective of the disease extraderminal disease. Important to know about the resectability the two areas which I don't resect or send for a neoadjuvant chemo that's infiltrative disease of port and root of mesentery superficial disease is resectable so it requires intraoperative assessment whether it's laparoscopy or it's an open operation to feel it actually to see whether you proceed or not with neoadjuvant or primary surgery fitness it's an objective assessment but one thing to remember if you optimize patients become fitter so you should not deny the opportunity of primary surgery when they can be made fitter. We shouldn't go there are two big debates neoadjuvant or primary and complete versus optimal I think they have been nullified basically because both these RCTs were conceptualized way back in 2004 even before those Dennis Chee's paper of abdominal upper abdominal clearance started coming up in 2009 and 10. So basically what the the the conclusion is NACT is non-inferior to suboptimal primary surgery when you can't do it but an optimal primary surgery is always superior to NACT. There's one thing I want to say here that people try when they don't have much training or they just think about the studies it's easy to do give NACT and they want to compensate with high PIC but the overall survival if you look NACT plus high PIC is not superior to primary debulking surgery and I think this is a very important message as you can see the the the lion study when they do primary surgery the control arm and overall survival of 60 months when you have high PIC with ideas is around not not that much actually so I think that is something that you should not compensate with giving high PIC and do NACT rather than doing primary surgery. So these are a lot of factors but that if you're giving NACT you really need to document the reasons for NACT and there are a lot of things resources patient choice performance status co-morbidity this is distribution but generally speaking what my my feeling has been that if people are used to do neoadjuvant chemotherapy quite a lot 70 percent and when they do primary surgery their surgical type is also like THPS omentum little bit of notes not many whereas if you have a center who does 60 to 70 percent primary surgery and that's the trust study you normally see that people go all guns to even debulk in neoadjuvant chemotherapy based on the initial disease distribution and not what you see after chemotherapy because you have disguised. So basically sometimes outcomes are better for isolated if you can do even if there's a little bit of residual disease left compared to no residual disease with NACT every amount of cytoreduction does increase your survival. So in our setting if it's more than age with large comorbidities NACT is non-inferior to incomplete primary surgery but I don't think people become any fitter to do a big debulking after so we really need to have an approach which might be minimalistic at some in certain cases. Some disease is not resensible truly not resensible NACT can make them worse fibrotic and all so you really need to think that whether at that setting you can remove it if progressive disease I think we are clear we should not do any surgery. If a patient has got excess burden and it is fit and you're doing NACT for the burden thing but it's resectable perhaps then you need to do the operation based on the initial disease at presentation and not what the post chemo CT scan and in all other cases perhaps consider primary debulking surgery. I think there is no the denial that if you can do complete you should go for complete but one thing to remember it is a maximal effort cytoreductive surgery. I think still you should not deny the benefit when of your perception that I cannot reduce in one area to less than one. So basically a lot of things are important for interoperative decision making in my personal series I have seen if I'm trying to do new ideas in cases who are really non-resectable to begin with I see more CC3 or residual disease after resection compared to primary where you can really take them out much more easily. This will a future upfront knowledge of tumor biology help in deciding optimal cytoreduction we're still not there. So debulking operonicity as we have seen in this case initially it was stuck to the liver unless you do the complete mobilization you couldn't see the plug and the plug was so very difficult to take out so I need to change my plan of operation because it could have bled and it did bleed when I started to peel off the glycine capsule. So it's more difficult more suboptimal cytoreduction and dilemma when you have high PCI scores and poor chemo response how much to do and 25% of the scars or the presumed normal areas have disease so we need to be very careful. So that was planning the second is execution and it is a multidisciplinary team approach and everybody patient the team and needs optimization and a recovery plan in place. You cannot do ERAS for every case. I think what I wanted just to say again the communication is very important in every maintain a calm theater environment and surgeon if they're hungry angry lazy and tired need to halt. I think there's no point in carrying out 10 hours when you are really struggling you just need to break in between. In James Cook hospital in UK where we have its original trauma center we've got a helicopter pad we have three robots there is a regional center for cardiothoracic and neurosurgery everything transplant but the debulking surgery complex is the most complex surgery as far as the resources needed in that setting too so it needs really close vigilance and this is a very important slide from IGCS that it's not only training doctors you know other specialties sometimes lack and we need all of them to get trained in order to be able to do this not only doctors. Who's doing it? Who understands the biology and philosophy? Earlier on we wouldn't be doing this but now we know the surgeons do leave this behind because in colorectal terms you wouldn't touch them. So ESCO quality indicators suggest a specialist who dedicates more than 50 percent time in gynecological cancer care anybody who's trained and who's dedicating this amount of time to do this work. Healthy literacy is very important and the sequence as I say I always do quadrant by quadrant evaluation but start with momentum because it reduces the fluid loss and it makes the patient is better maintained then I start the upper abdomen because pelvis bleeds and if they are becoming unstable then you compromise in a lot of upper abdominal procedures also you need to put your hand and press on the liver sometimes it's quite difficult at the end of the operation so I really try to deal with this part before pelvis I know I can always debulk. For every PCI generally it takes about an hour so basically that's what I kind of alert my anesthetist at the beginning of the operation. This is a paper I wrote with Bill Helm 140 patients both UK and India the largest series of looking into metastatic involvement in lesser sec and you can see that all these areas that upper recess, caudate lobe, ventricular pusture surface, groove of ligament and venosum, floor, subpyeloric space, splenic hilum, transverse mesocolon, pusture so all these things all these places they need to be looked into thoroughly because you do find disease and 60% in advance most of this disease is small so if you don't look them carefully you miss it and that's why we were looking so we're doing an open operation opening the space and putting a laparoscope to magnify so that you can see and then you can treat at the same time ablation or resection and these are the survival results NGOC Gateshead and TMC Kolkata and you can see a comparable progression free survival at least and the complication rates as well so it's doable. The other thing I started doing after coming from MSK was to look into the thorax and you know most of the time you know it's a dependent it's a gravity dependent thing the peritoneal fluid wherever it hits from right to left you know the right appendix and the hepatronal pouch and then the liver most of the the recess you hit in here then the foramen of Winslow you find the lesser splenic hilum usually you don't see on the left diaphragm and the outer surface of the spleen similarly in the thorax with the diaphragmatic you know the most pleural nodules are on the diaphragmatic surface and some of them on the lower right but you don't see on the apical surface pulmonary disease is very rare and it should not be confused with the pleural disease because this is treatable. So you need to do all these things in a standard debulking surgery you know bowel spleen peritoneum diaphragm mensum necessary but structure documentation is required. This Puram has already mentioned and I really liked Dennis's point that they had a beautiful like you to kind of download this paper it's a very important paper because they talk about fats they talk about even hythoc hyperthermic intrathoracic chemotherapy and abdominal findings intrathoracic findings but if the abdomen is receptable irrespective of thorax you should do an abdominal resection, whether it's after anesthety or a primary. So don't stop doing abdominal resections. ESCO guidelines, I think every fellow need to read. There are only very few indications where you would not do abdominal debulking, and these are diffuse deep infiltration of root of mesentery, carcinomatosis of bowel, which is beyond 1.5 meter of the bowel, diffuse deep infiltration of stomach, jejunum, pancreas, but involvement of celiac, hepatic artery, left gastric arteries, but celiac can be resected. Metastatic 4b, and these are only where they are resectable. However, if you've got multiple parenchymal liver, multiple parenchymal lung, this is different to pleura again, and non-receptable lymph node, multiple brain meds. Apart from that, I think you should give a go, and primary surgery, you know, if you can, if you can't, the neoadjuvant, but if they have got response to stable disease or some response, you should do, only with an exception that if it's progressing on neoadjuvant chemotherapy. Potentially receptible extra abdominal disease, you should resect, and all these things. It's very little that you should not do really, and then there is a minimum required information, especially very important structured, all areas, complicate mentioning, size, residual disease, at the beginning and at the end, an operative report, pathology report, and if you have not resected or evaluated document, why did you not look into that area? Why did you not resect? There are situations where you have to do, but it's good to be transparent. As for guidelines, Linus, thank you very much for giving me an opportunity to be part of this two-year process, and I learned quite a lot, how to do the evidence, look for it, and I realized that reading a guideline for half an hour, just the crux, and doing a guideline is so different, and I think even here, it would say patients with biopsy proven stage 3 or 4, which includes high tumor load, stage 4b, poor performance status or a receptible disease, you give neoadjuvant chemotherapy, and then there is, if there is response of chemotherapy or stable disease, you do interval cytoreductive surgery. Quality of life, about 247 globally, I contributed to 52 from Tata in Kolkata, and we have, it's shown that even with high complex surgical score, complexity score, the quality of life is no different, so therefore, it is no worse than patients undergoing extensive surgery in the immediate, medium, long run, and Soccer India study continues here. A little bit about quality improvement, because that's what I've been talking, so whenever you start a process, like whether it's hyping, whether it's cytoreduction, you go through a quality improvement program, which I did in Tata in 2015. It was only at the end of it that the NIS guidelines of ESGO quality assurance had come, but I had started using data, MDT protocols, reflection, risk management, and continuous medical education, audit, and research, and that's what I'm trying to teach Poonam for the short period that she's here. I can't teach her surgery, but she could at least learn this bit, and then you need to do a capacity building exercise, because you need data management, you need social workers, nurse specialists, and you know, all these things and collaboration with every other specialty in your hospital. So that's what we published in 2016 in IGCS, change of paradigm at that time, people were doing more interval debulking surgery to change to primary, and then from optimal to complete, and it does require a lot of changes, and the struggles which come, and denial from other people which come with it. So this is the result which we found initially when I was in the center, there were not trained gynecologists, there were gynecologists who were practicing an 80% new adjuvant rate, and you would see disease coming back within six months was about 42%. So that's where we started, and I took a stand that yes, complications will be higher when you start, your complexity goes high, but then you learn how to manage the complications, that's the black bar, this is a survival. So eventually, when you start managing the complications, the gap increases, and we had to prove it, and that's what you see when you initially start death in first six months, we had two, but then gradually, gradually, you know, your grade three, four complications go down, your death goes down, and then what you found here, that when you take a strategy of putting 70 to 80% in primary debulking surgery, now the disease coming back within six months is about 7%, i.e. now most of your patients have a platinum sensitive records, and that is a very important paradigm in treating ovarian cancer. Once you put a stamp of platinum resistant, you run out of options. So that's what you achieve, but then you need a local protocol, because in our setting, we have a lot of gut microbiome problems, SARS and infection, so you really need to tweak a lot of things from your ERAS protocol, MDRO very much present, which I published or projected in IGCS in Rio, and then you keep on publishing your things about diaphragmatic surgery. This is something I kind of really want to show. I don't know if I can go in here. Let me do control and click. It's not working. Anyway, so basically, this is like when we started following the ESGO 10 quality indicators, and I will come to that slide, and we were compliant with that, and that is why after three years, we were the only center in India, well outside Europe, to obtain ESGO accreditation, but that was hard work. Most of it required documentation, and if you can see, and this is very important for everybody, what you need to do in order to be audited so that you can do these high-risk procedures like high-pig and all that stuff. So basically, complete resection rate, your target is 65%, right? Proportion of primary debulking surgery, this is stage 3 and stage 4 cancers, should be more than 50%. This is what we have been doing recently in my new center from last year. We're still reaching there. How many surgeries a center should be performed? Optimal surgery, this is stage 3 and 4, is 100, and then you've got intermediate and minimum, and 95% of surgeries have to be performed by surgeons operating at least 10 a year. That is independent. Number of surgery performed by, so basically, patients with advanced or worrying cancer operated on by a specialist, more than 90%. Center participating in clinical trials, very, very important. There is no target. You just need to do it, and then treatment reviewed and planned in MDT has to be more than 90%. That's why we put every patient in MDT. Required preoperative workup, more than 95%, which is documented. Post-pre and operative management, you've got a perioperative program, which needs to be established. You need a minimum required elements in the operating notes. You've got an SGOF note, and you really need to be very stringent that it contains all the required elements, including the reasons if you did not do 6 to 0 in a quadrant or you did not evaluate. Minimum report required in the pathology, I have seen the department grow from handwritten long reports, from now the printed reports following all the criteria, and you need a post-operative complication planning and database collection. Without this, you should not be doing these operations. It's as simple as that. So that's why the first thing I did in Tata is to put in a program, a research program, a clinical trial, so that every patient could go into it because it improves your documentation standard and your quality of care, and then immediately you start seeing improving in your survival in your primary surgery group compared to your neoadjuvant group in all states, intention to treat, bar protocol, excluded, and all patients. In our setting, it's really important that our patients are younger. So basically, I say it's a curative intent, but it's a stage 3, 4 disease. It requires big surgery. It's high risk and high reward. I have taken this word from Dennis Chee. 5% open and closed rate if you're not doing laparoscopy. It can have suboptimal surgery, but there are some options with high complication rates. Any complications, major complications, mortality is there higher when the program starts, but if you start putting 80% in neoadjuvant chemotherapy with the sick patients, you will have a mortality as well in that arm. Often that does not get reported because we collect our data from IDS and PDS, but not from the beginning points. So basically, it's not only doing surgery. You need to have economics, quality of life, and translational because good biology does not compensate for bad quality surgery. And that's what we have been doing, looking into HRD and other biomarkers, CRS scoring, even as a biomarker. And this is a study, which I say that don't do high-pick in everybody, but find out the subgroup where it's going to be beneficial more, especially, specifically if you don't have the paper apart. So that's called targeted high-pick, but even to go to the program, you need to achieve a standard of your operation and documentation before you go in a trial, because that's what I'm saying. In a low-middle income country, we cannot afford Bev Park. You need a degree of high-pick and IP, which might be the most cost-effective way. Of course, we're looking into the non-randomized study first, and then go for, in the future, if it works. And this is all based on my work, that not only 50% are HRD, but you can see in the HR competent group, they're difficult to start to reduce as well, because they have a difficult, different biology. So they don't respond to PARP. They're not good with platinum either. So what can you do? It's an unmet need. And that's why I think you need to do something which makes a cold tumor hot. I did the lab work, which shows heat does sensitize the BRCA-proficient cell lines to behave like BRCA-deficient, and they are responding to PARP inhibitors more. So basically, that's what the hypothesis was, that it might be targeted selectively in this group, and that it's testing the hypothesis. And this is the primal study, which Linus will see. So basically, what you see, near and far to everybody, when patients have 67% IDS, in HR competent arm, you increase the survival of BFS from 5.4 to 8 months at a cost of 40,000 pounds. Of course, in HRD, there is no question about the benefit. In my data, in this group, we did not have any PARP inhibitors. We are doing 70% PDS in date set. So we had a figure of eight months. I would be very happy to see, even at three months, BFS benefit with high PIC in this group, with a cost of 1,000 pounds compared to 30,000 pounds. So this is the study, stage three, stage four, PDS, IDS, because we all stratify. And then, basically, just a couple of slides. This was my interview presentation in UK, achieving excellence in the treatment in a health service with finite resource. The NHS, it has, it's a health service. So I say that excellence is always infinite, and resource is always finite. So therefore, you need to be creative in order to do decentralization, centralization, and a lot of other things. But when people talk about resource, manpower, I think, is the most important, and that is why we have this IGCS or other training programs. You need to fix both skills, but most important is operations. And most of the reasons why we are not doing what we are supposed to do is not because of the skills, but because of the operations and attitude. People don't want to stay back, or it's a long case, or it's difficult, or, you know, so many other excuses, really. So this is my conclusion. This is a surgery is the mainstay. It was one of the most complex surgeries in cancer treatment. It needs like a transplant surgery. It's not a one-man job. It's not a heroic job. It needs a team, dedicated setting, infrastructure, evidence-based rather than convenience-based. And if it has a good outcome, it can be achieved if referred to specialist services earlier. To refer early, don't half operate, don't disseminate. And for the patients, because I am a patient advocate, everybody should check the credentials of the sensor, and also the surgeon. Are they trained, qualified, have they been doing it? I think in this day and age, we cannot skip that, and therefore, again, importance of getting trained all around. So with this, I will stop, and thank you very much once again.

cytoreductive surgery

ovarian cancer

quality indicators

training

surgical team

PARP inhibitors