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Ashish M. Kamat: Welcome everybody to UroToday's Bladder Cancer Center of Excellence. I'm Ashish Kamat from MD Anderson Cancer Center in Houston, and it's our pleasure and privilege today to welcome Dr. Rafael Sanchez Salas from the Montsouris Institute in France. Dr. Sanchez Salas is a well-known entity in the urologic oncology field. And today he is going to talk to us on his perspective on radical cystectomy. He's been a champion of recognizing that oncological concepts across the field are more important than the minutia of surgical technique. And today he's going to focus his attention on radical cystectomy and how this applies to our bladder cancer patients. Dr. Sanchez Salas the floor is yours.

Rafael Sanchez Salas: Thank you, thank you very much Ashish for, for the opportunity. Thank you for your comments and thank you for the UroToday team — it's really a pleasure to be here, and we're going to address, as you mentioned, the importance of oncological concepts in radical cystectomy and how this goes beyond the actual technique. So just go back to some bladder cancer facts, to start. And as we know, the second most common GU malignancy is bladder cancer, and it has a high number of new cases and deaths, there are estimated for this current year. Radical cystectomy remains the standard of treatment for those patients that are harboring muscle invasive bladder cancer and or recurrent high-grade non-muscle invasive bladder cancer, so it's the cornerstone of surgical technique for those patients. That being said, radical cystectomy is a procedure risk, very related to a high risk of complications and adverse, both oncologic and functional, outcomes.
If you look, since a long time ago, we have known that a radical cystectomy is related to heterogeneous outcomes and those outcomes depends mostly on the stage in which disease is diagnosed and therapeutically decided to receive surgery. There's a key role for the oncologist. In today's world, we just need to acknowledge that there is some treatment around radical cystectomy that really will severely impact the outcome. So there's some of the neoadjuvant treatment protocols available. As you can see, there is the MVAC and the GC protocols that were out since many years ago and not fully embraced by the urological community. And more recently, we have new protocols, including immunotherapy, and these protocols are completely changing the picture of the actual oncological outcomes for a radical prostatectomy. Certainly, we have the robotic cystectomy coming in. Robotics has become the real evolution in the surgical field.

We know that robotic cystectomy has been defined as perhaps an ideal approach in frail patients because it represents minimal invasion that was completely inherited by the laparoscopic approach. Also, it reduced trauma and surgical stress. There's a real benefit that perhaps related to the intracorporeal approach that as we know, cystectomies clearly related to our records... the reconstruction part, and there's risk reconstruction when it's done intracorporeally. It has been related to a real benefit. At what price? That we don't know. And actually, when you look at the operative times for those initial series, doing intracorporeal robotic approach, we can see there is a lot of exposure over time and this raises questions in terms of the eventual training or the new generation of surgeons will have. So we know that intracorporeal approach versus extracorporeal has been compared.

And there are some higher complications and readmissions for those patients that are actually exposed to the intracorporeal approach when this is initially performed, because there is a steep learning curve. We cannot forget about this fact.

This is a recent manuscript. This is our experience where radical cystectomy, and this is 300 patients that were operated at our center in Paris between 2007 and 2019. I checked, it was to compare a laparoscopic or laparoscopic experience, or is a referral center for laparoscopic urological oncology surgery. And we compare our initial laparoscopic cases with robotic cases and found pretty much no differences in terms of the complications and the early oncological outcomes. Some nuances we can tell, we know that, for example, the [inaudible 00:05:31] was shorter for robotic patients, but we know there was a learning curve before we actually moved to robotics from laparoscopic.

And it's important to say that these patients, since 2008, were receiving neoadjuvant chemotherapy, all of them, that was the policy of our institution. So it is very important to clarify the concepts. And then for this, we have two studies, two major studies. This is a study from an already strong caddy for Bernie Bochner, showing us a randomized comparison of open radical cystectomy versus robotic laparoscopic radical cystectomy. The oncological outcomes show no actual differences in survival outcomes. When you look at the numbers, there's 118 patients, but the techniques — are they actually comparable? There's a problem with the techniques because there's open versus actually some part of the robot that the prostatectomy done with the robot and the reconstruction done open, which is something we can eventually argue.

But the most important thing is that no, there's no difference in survival outcomes. And this is what really matters to our patients.
We cannot forget about the RAZOR Trial. This is a trial that is led by Dr. Parekh in Miami, and he is at 300, over 300 patients that once again, if you look at the curve, there was no difference in recurrence in the three-year progression-free survival, three-year overall survival for robotic and open radical cystectomy was the same. So oncologically speaking, we are in the same arena where it's completely comparable. Once again, in the RAZOR Trial, the reconstructive part for the robotic arm was done openly. So it's one of the arguments to people can have against the studies, but once again, we need to remember that oncologic outcomes are the main objective and those were comparable.
So robotic cystectomy, as we can see, represent in the assessment from the IRCC in 2016, we see that most of the urinary diversions done our intracorporeal ileal conduit and intracorporeal neobladder is only done in 17% of cases.

So this is kind of a thing that happened before for a procedures like laparoscopic or a radical nephrectomy where perhaps we're indicating a diversion that is more related to a less complicated technique rather than that diversion that is more adapted to the patient. And this is something that is somehow worrisome. So, important issues are there in radical cystectomy, beyond the technique. Those is important. These issues are related to patient's characteristic. We need to, before everything, look at the age, comorbidity, are these patients frail? Are these patients having a nutritional status that are adequate in terms of albumin evaluation before the operations? Obviously this is characteristics are of utmost importance because from the start, we know that these will have a clear impact on the actual outcomes.

Functional characteristics, the patients need to be aware of how the pre-operative sexual and urinary baseline is going to be impacted by it, by this operation. That's, as I said, is a big surgical trauma — and even if robotically performed, it has a clear impact in quality of life. And important factors like neoadjuvant chemotherapy previously comment that we certainly believe that these benefits that patients have when having neoadjuvant chemotherapy are something that you need to discuss with the patient. And obviously more recently that the ERAS protocols, there are definitely changing the possibility of results of these patients, especially in their 30 days and 90 days post-op. And, of the most importance as well is the training of the generation. How are we trying to transmit our robotics or open skills? Is there a robotic availability? Can we just believe that if there is no robot, no cystectomy should be done? Do we really have the time to provide hands-on access for each one of the people that we're trying to train, especially on the context of a very steep surgical learning curve?

So these are the questions that we have, and we need to remember that for the pre-op evaluation of the surgical candidates, team work is essential. We have to just pay a lot of attention to the extensive explanation about the oncological outcomes and the surgical approach discussing about the urinary diversion, how this is going to impact quality of life, discuss, obviously in the continence and sexual function, counsel patients and their families on the psychological impact that the operation can have. Counseling also on the stoma, the difference between the ileal conduit, self-catheterization for neobladder, the different situations that the patients is going to be exposed after the procedure, and obviously try to provide an evaluation with official therapists in terms of to train or prepare the patient for the operation before this actually happens. Preparation for surgery includes not only this counseling, but verify, the nutritional status of patients, and verify that the patient is ready to go to this kind of a marathon, surgical marathon they will go through.

So biology prevails, and this is what our message is, the true advances in the outcomes for patients having radical cystectomy are going to be really more related to an improved understanding of the biology of the disease, understanding how this is going to be evolving if we do things wrong from the first time. And obviously a comprehensive and multimodal approach is, today, what we think is the best way to go. And we need to strongly think about how to improve patient's survival and patients quality of life. Thank you very much for the opportunity. Thank you very much, indeed.

Ashish M. Kamat: Thank you, Rafael. That was, that was very good and very concise. And I agree with a lot of the points that you made. For the benefit of our younger members of the audience, perhaps, people that are coming up in training, residents, fellows, you raised some important issues. How do you approach your training of your residents and fellows when you're trying to get them to understand the balance between recognizing the importance of biology and of course, their desire to jump on the latest technology. What's your approach to training them?

Rafael Sanchez Salas: That's an excellent question. We are a center where hands-on, as a concept, is very important. Obviously, most of the fellows we train are people with a background. So part of this discussion on their selection is done on an everyday basis. When we all are in the OR and we just love to listen to their criticisms about, or decisions that were made before patients come to the OR. And then when you actually are in the OR, we try to expose them, they're clearly exposed to radical prostatectomy on an everyday basis in their woods, much high numbers and what we have for radical cystectomy. So they get a clear understanding and how the robot works and how the learning curve for the machine to control the machine is achieved.

And then they need to understand that for a big difference, just to give you an example, lymph node dissection is an essential part of, of radical cystectomy, and they need to understand that this is not just a very big game, but it has to be a sound and complete dissection. They will have an impact on quality of life. So they initially exposed to a lymph node dissection and on a step and step basis they will go for the more difficult parts, for example, the pedicle dissection of the posterior part of the prostate. Because even if they're supposed to do prostate surgery, we know that when the bladder is there, the surgical picture is not necessarily the same.

But this is just to summarize. It's a step by step approach. And obviously, we do have open cystectomies, and I do open cystectomy. I have no back thinking about deciding now, an open cystectomy, if I think it's better for the patient, and it will eventually do obtain the same oncological outcomes while exposing patient without for, or less, morbidity in the OR for example. So, they are exposed to both open and robotic cystectomy, much less lab in these days.

Ashish M. Kamat: Yeah, those are great points because I completely agree. What happens with a bladder cancer is that it's important for people to recognize that the biology, as you said, the margin positivity, the T3/T4 disease, the adequacy of resection is most important. And if you can do the procedure open or robotic or laparoscopic, or however, so long as you do it oncologically safe, the patient benefits. But what happens is if you try to get everybody on the learning curve, and then you have positive margins, or you don't remove enough nodes, that's when the patients really suffer, because there is no remedy for bad surgery in general, but especially when it comes to dangerous cancers like bladder cancer, right? Now at your center, do you tend to use neoadjuvant chemotherapy or more adjuvant therapy?

Rafael Sanchez Salas: No, we do definitely use neoadjuvant chemotherapy since many years ago, 2008, we started with our prospective evaluation of neoadjuvant chemotherapy. It was initially, it depends, it depends on patient characteristics. We'll go for MVAC, or Gem plus cisplat. But this is something that is clearly indicated for every patient that we have no discussion on the T2 cases. They go for neoadjuvant chemotherapy, as we believe that 10% benefit that was clearly criticized by some colleagues around the world is clearly a benefit, a short benefit for the patient, but they will add up with some, especially in the area of minimally invasive surgery. We have the benefit of neoadjuvant and the less trauma with minimally invasive surgery, where so we thought since 2008, there was a good symbiosis between those approaches.

Ashish M. Kamat: Great, great. That was going to lead into my next question because clearly, where biology and technology come together in oncology and in bladder cancer is when we are looking at the gene expression profiling, and the subtyping, and using genomic technology to try and understand the biology of the patients better. What is your sense of where technology and genomic technologies headed when it comes to the biology and how we should treat bladder cancer patients?

Rafael Sanchez Salas: Wonderful question. I think definitely with genomics, we're going to be able to define those specific micro-propeller genotypes, and define exactly the situation of the tumor before we treat the tumor. This is something that's been going on in other areas. Psychology, just for example, lung cancer. Patients are not even treated before they have a genomic evaluation, and this is why we want to see, we love to see in bladder cancer, because we know that obviously the more information we have, the more information we will use to deploy our therapeutic armamentarium. We will be a little bit on the back in Europe to have access to this armamentarium, genetics evaluation. This is not something that is easy to access in Europe, but definitely when we have centers around, like in Italy or even just in Paris, Gustave Roussy, Institut Curie, they definitely do a lot of research in the area. And our idea always to try to work with them, to find ways to define the genetic situation of patients before we decide for natural treatment, active treatment.

Ashish M. Kamat: Alright. Rafael, this has been a wonderful discussion. There are obviously a lot of more questions I could ask you, but in the interest of time, maybe I could have you just give the audience your closing thoughts on this topic?

Rafael Sanchez Salas: Well, I thank you again, thank you again for this opportunity. And once again, our messages that obviously we clearly defend robotics. We think robotics is the present and the future, but when we do oncology, we need to realize that not instrument goes beyond the actual biology of the disease, and this is our message today.

Ashish M. Kamat: Great. Thank you again for taking the time to be part of this important educational activity.

Rafael Sanchez Salas: Thank you so much. 

Ashish M. Kamat: Especially during your vacation. Stay safe and stay well.

Rafael Sanchez Salas: You as well.