Alicia Morgans: Hi, my name's Alicia Morgans, and I'm a GU medical oncologist at Dana-Farber Cancer Institute in Boston. I'm so excited to have here with me today, Dr. Fernando Korkes, who's an assistant professor and the head of the Urologic Oncology Division at the ABC Medical School in Sao Paulo, Brazil. Thank you so much for being here with me today, Dr. Korkes.

Fernando Korkes: Thank you for receiving me here. It's a great pleasure, a great honor, to be here and present our results at UroToday.

Alicia Morgans: Wonderful. Well, I am really honored to speak with you, because these are incredibly striking results, and results that I am very proud to speak about and to give a forum to. I'd love to hear about your recent publication. This was in the JCO Global Oncology journal, where you and your team presented information from a multidisciplinary bladder cancer clinical practice that you recently initiated in Brazil. Can you tell us a little bit about it?

Fernando Korkes: Yeah, sure. Our data demonstrate the results of our program. The background was a scenario where patients with muscle-invasive bladder cancer had very high mortality after treatments, and mainly after surgery. That's not exclusive to our service. That's very common in developing countries. We don't see much of that data in the literature, because that's not published. Nobody wants to publish bad results. And also, journals don't want bad results to be published. That's a tough reality, but that's what happens.

Fernando Korkes: We don't see that in the literature, but we see that in real life, in developing countries. After noticing that in our service, we thought we had to do something to change that scenario. We started to study what were the main reasons that led to those poor results? And what could we do to change that? That's the background of all that we did.

Fernando Korkes: And then after a while, after several years, we compared the results prior to our program, which we call the CABEM project, and the results after establishing the program. And what we found is that the results were amazing. Without great money investments and just organizing what was done, we could change a lot for our patients, and it's very good for everybody.

Alicia Morgans: I agree. I think this was really striking. Let's just back up for a moment and you can tell everyone, who was involved in this multidisciplinary group that you put together to review cases of patients with muscle-invasive bladder cancer? And how did you meet? How did you have a quorum, and talk about these patients, to give the best advice?

Fernando Korkes: The first person that noticed that there was a problem was Professor Sidney Glina. He's the Head of Urology, Chief of Urology, of ABC Medical School. He was bothered by the results and what was happening, and he was the one that called me and invited me to go to the service and start a program in GU oncology, and also in bladder cancer. He gave the start to everything.

Fernando Korkes: Then we have a great team of urologists with us. So Dr. Frederico Timóteo, Dr. José Santiago, Dr. Reddy, Dr. Marcel, Dr. Eduardo Pedroso, Dr. Marcello Gava.

Fernando Korkes: We have also a great oncologist, that's Dr. Suelen Martins, and she's always with us. We have a large number of radiation oncologists that we can also count on. And also, we have two physicians, one from the US, and one from England, that we could share experiences, Dr. Prashant Patel from Britain. He was not responsible, but he studied a lot, the centralization program that happened in England. He helped us to establish our centralization program. And Dr. Phillipe Speiss, he is also a great friend and everybody knows him, and he also helped us a lot to improve our ideas. That's the team.

Alicia Morgans: That's fantastic. I love that you were able to bring people together and discuss these cases. What is interesting too, is that you had a comparison between the outcomes of patients who were enrolled after you put together this multidisciplinary program, to historical control population that was treated at the institution previously. And there were differences at baseline between these two populations. I'd love for you to just explain, how did cohort two, actually, that was the newer population that was seen by the multidisciplinary clinic, how did that differ from cohort one that was the historical controls?

Fernando Korkes: Yes. Well first, we noticed what we did and what physicians did ... So we are talking about the ABC region. So ABC, it's a region near Sao Paulo. That's a region that comprises around three million people. So, it's a very large region, and there are some hospitals, some public hospitals, that receive patients, and many hospitals just treated these patients and operated on these patients and did radical cystectomies and all the surgeries, and many times without having the appropriate conditions to do that.

Fernando Korkes: So what we noticed is that sometimes intrahospital mortality was as high as 50%. Imagine you being a patient, you go to a hospital to treat cancer, and you have a 50% chance of going back home. It's not acceptable. So the average mortality was about 40% for all the hospitals. So, we thought it was not acceptable, and we started to try to understand what to change.

Fernando Korkes: All that these physicians had by the time, was surgery. This is not easy to do like new advanced chemotherapy prior to a radical cystectomy in the public setting, where many patients take four, five, six, or 10 months to get to a physician. So, imagine a patient suspected of bladder cancer, that takes almost a year to get to a urologist. Then another year to get to an oncologist to get neoadjuvant chemotherapy. It's not possible to undergo. So everybody was treated through surgery. Patients, 80, 90 years old, patients with T3, T4 disease, irrespective of their clinical conditions. So, that was the only treatment that was given to those patients. So that's a reason why the cohorts were different.

Fernando Korkes: After establishing a centralization program and a multidisciplinary approach, we made it possible to start doing neoadjuvant treatments, to start doing trimodal therapy. So, we started to have other options for these patients. If you look at the different cohorts, cohort two, that was the cohort that was treated after the institution of the program, they were older. Patients were older. Because we have right now, the condition to give older patients curative treatments. So that's one of the reasons. And also, these patients tend to have more comorbidities and higher Charlson comorbidity scores. So back then, patients were younger, they had less comorbidity, and yet, they died more.

Alicia Morgans: And I think that's one of the things that is so striking. And as you said, the 90-day mortality rate in cohort one, the historical controls, was around 35%, versus in cohort two, it was 5% after you instituted this. Even though, the patients in cohort two were older with more comorbidities. You also, as you said, were able to give neoadjuvant chemotherapy. Fewer patients got cystectomies, but maybe more appropriately, some patients ended up with transurethral resections and others with maybe, systemic therapies. So really, you were more able to appropriately get the treatment, that's the right treatment to these patients, and reduce mortality.

Alicia Morgans: And one-year mortality was also better, significantly, in your novel cohort. So this, in all respects, was an improvement. And certainly, you and your team should be commended for saving the lives of these people, and keeping them with their families in their homes, and hopefully, curing some of these patients of their disease, and helping others be more appropriately treated. So if you had to give a summary or a general conclusion, what would that be? This is again, I think, quite an impressive approach for your team.

Fernando Korkes: First, it's important. To summarize in one word, it's important to centralize in specific centers. So, that's very important, mainly in developing settings. So what we noticed is that we, in developing countries, we respect a lot, what is written in guidelines, such as AUA guidelines, European guidelines, NCCN guidelines. That's what you mainly see in developing countries. So if it's written that a patient with a T2 disease should be treated to undergo a radical cystectomy, and an intestinal diversion, that's what you see that is done in most settings, irrespective to the clinical status of the patient. But what we noticed, that even though that was written in guidelines, that's written in the developing world, if we go to papers, like those published by Dr. Stephen Williams, you talk to him, and several other papers that study epidemiologic cohorts, that's not what is done to most patients, even in developing countries.

Fernando Korkes: Most patients with T2, T3 diseases, do not undergo curative treatment. Not because of the impossibility, but because sometimes, the best for these patients is not a very radical treatment, because they don't have the conditions to undergo this treatment. So, we have to tailor each treatment to each patient, and maybe for some patients, radical cystectomy and a neobladder is the best treatment. But sometimes it's not. Sometimes it's trimodal therapy, or even exclusive radiotherapy, or palliative chemotherapy. I don't know. We have to tailor it to the patients, their age, and their comorbidities.

Fernando Korkes: So what we could notice, is that we should not always follow exactly what's written in the guidelines. We should tailor that for each patient. And that might sound something controversial to say, but that's what's done in the whole world. So the guidelines are very important, but we have to know why we are following the guidelines, and we have to know when we should not follow them, so that's how we managed to change our results. What we had back then, is that people could not follow exactly the guidelines, like neoadjuvant chemotherapy was not offered to anybody, but surgery was offered to everybody. But that was not bringing good results. So, I think we have to tailor the results to each region, to each patient, to each scenario, and having specialized centers helped the results a lot, I think. For complex diseases, such as bladder cancer, that's pretty much a reality that has been shown in several papers.

Alicia Morgans: Well, I could not agree more with that sentiment. That really, sharing the knowledge, working collaboratively as a multidisciplinary team, and extending from our centers of excellence into our communities, and raising the level of engagement, and the level of knowledge throughout, is the way that we take what's written in the guidelines, and really use the art of medicine, to tailor that to each individual person sitting across the table from us. Because that's how we need to practice. And that's how we do the best that we can for these people who come to us with their trust and ask for the best treatment for their cancer.

Alicia Morgans: So I commend you and the team for doing this. I think that you clearly have made a difference in Brazil, and in that area around Sao Paulo. And I hope and expect that you can continue to make a difference, as you extend this approach throughout the rest of Brazil, hopefully, and much farther than that.

Alicia Morgans: So thank you so much for this work, for this innovation, and for reporting that back to us. We appreciate it.

Fernando Korkes: Thank you so much. Again, it was a great honor to be here, and a great pleasure. Thank you.