Ashish Kamat: Hello. And welcome again to UroToday's Bladder Cancer Center of Excellence. I'm Ashish Kamat, Professor of Urologic Oncology at MD Anderson Cancer Center. And it's a distinct pleasure to have on this platform, once again, Professor Andrea Necchi, who's been with us many, many times before. He's talked about papers, research presentations, debates, et cetera, et cetera.

But today it's a pleasure to have him here to ask him to discuss with us a more broad topic, which is the retreat that he had at the San Raffaele Institute in Milan just last month. This was a great meeting of interesting researchers and interesting projects, and just a lovely occasion to get people interested in urologic oncology to come together.

And Andrea, I wanted to ask you, so if you could just kind of share with our audience the purpose of the retreat? And what you were expecting? And did the retreat meet your expectations?

Andrea Necchi: Thank you, Ashish. Thank first of all for the opportunity to be here and to be interviewed by you. It's always a pleasure. And thanks to the UroToday people for hosting this interview.

Yeah, as you mentioned, we hosted this year, on November 25, the first edition of the retreat, the San Raffaele Urologic Oncology. Basically our aim was to gather people and key opinion leader from worldwide, and sit down on a unique shared table.

Trying to discuss not just what is going on at our center in terms of trial pipeline and research project pipeline, which is basically the usual aim of any retreat, but open the door at the same time to what is going on and what is being pursued by key leaders and key group leaders in urological oncology. And trying to identify a way of potential collaboration, or improve ourselves based on the models that have been pursued by successful collaborators and the successful investigators in the uro space.

And I think that this aim and the spirit that will surround also the next editions, that hopefully will be hosted in the next years, not to look too much at ourselves and what we are doing internally in terms of clinical trials and in the projects, but trying to see, to look abroad and to enlarge the spaces of collaboration towards new people.

And potentially involve new collaborators and potentially look at the areas of collaboration in which, for example, there is an unmet need. Or in, for example, looking at the often disease areas, or often disease, often geographical areas. Or many aspects that are surrounding the clinical research in the uro oncology, most of which have been debated during the meeting.

One important point that emerged from the presentation was the fact that we are at the forefront in general of the developments in this space, in uro space in many disease, in terms of new drug availability, new clinical trial availability.

But as a matter of fact, we should consider always the fact that we are representing something like 20% of the worldwide availability of trials and availability of new drugs. Because for the rest of the geographical regions we are dealing with something that is completely out of the possibilities for patients and for clinicians at the same time.

So trying to be as much as inclusive as possible, and trying to coagulate as much as possible, not just patients but also colleagues, in our endeavor should be one of our priority. And this is also one of the aims of the retreat.

Ashish Kamat: Yeah. So Andrea, let's unpack a few things that you said, because you covered a lot of ground. So one thing that I really found refreshing and very unique about the retreat was that, yes, you did have your local investigators and experts present what was going on at your institution, but you actually invited a lot of external experts to share what they were doing.

And not purely from a scientific perspective, but how they have experienced their organizations, patient advocates, et cetera, et cetera. How are you going to take what you learned from that, and how would you advise someone that would do something similar, to take what you learned from that external input and help improve the internal processes?

Andrea Necchi: Yeah, great question Ashish. I think that the main lesson that I've taken from you and from all the participants to the retreat was the ability of establishing international connections and establishing and running international trials.

This is something for which we are still not fully prepared and not fully able to be in the good shape, in order to run and to promote such kind of collaborations. So that the international perspective, meaning the possibility to develop an idea, primarily an academic trial idea, for example, in a multinational fashion, and trying to establish a trial machinery that allows you to pursue this goal of reaching and pursuing important trials in an international setting is something for which at San Raffaele we are still naive.

Because we are, in particular in GU medical oncology, we are still in our infancy because I build my research group two years ago. So we are still at the beginning of the journey somehow. So this is the most important lesson to me.

And the lesson that I gather from you, and then for all the colleagues that participated to our meeting, and the main message and the main lesson that I've taken, this quality of being able to establish international networks.

Ashish Kamat: And Andrea, again, you've been championing that cause for a while and you've been a leader in your field. So that's very great to see.

One of the things that came about from our discussions at your retreat, I mean it's the Global Society of Rare GU Tumors, which you helped co-found with Phil, Phil Spiess. And then the IBCG, International Bladder Cancer Group, which you are part of. Just talking at the retreat and discussing ideas, we came up with this concept, of course, which you are going to lead, which is the rare variants of bladder cancer.

Because those have an unmet need, they're not part of clinical trials. In fact, they're oftentimes excluded from clinical studies because the appropriate sponsoring agency doesn't want to risk their disease approval for the drug.

And of course now we have a separate arm that is going to launch soon, that you will be leading with the Global Society and IBCG, rare bladder subtypes. So it's really excellent to have retreats such as these where you hear ideas from different people, because from that we can truly create new organizations, or create new efforts to help our patients. So that was really just one example of a great offshoot from the meeting.

The other thing that you mentioned, both at the retreat and even just now, Andrea, and I gather it's something that's truly a passion of yours, is to address this inequality that exists globally. But sometimes even within the same country, right? Because even within America, for example, there are parts of the country where patients don't have access to certain drugs, and there are parts of the world where they just can't afford certain drugs.

So you've sort of led the charge recently, through collaborations and white papers and discussions, on trying to address this global inequality. Could you share with our audience some of your thoughts on that topic?

Andrea Necchi: Yeah. I think that this is an important point of today, or today's practice and today's research. One of the reason for inequality is, for sure... Maybe for sure, the fact that patient is, for example, diagnosed with a rare tumor. You mentioned the rare histologic subtypes of bladder cancer. This is also applicable to other rare subtypes, or histological or molecular subtypes, or other urologic cancers.

And of course, the unavailability of trials and new drugs, and knowledge, and the lack of knowledge in rare tumors, is a reason for substantial inequality. In the way, for example, similar patients are treated worldwide in certain geographical regions as compared to other one.

And this is typical for, for example, penile cancer or testicular cancer. And this is the reason why, for example, in testicular cancer is recognized the fact that, for example, the cure in centralized centers of excellence is impacting the overall survival and is impacting the possibility of success in treating patients.

And this is the same basically, or maybe the same with less level of evidence, for other rare tumors. In general, the very high rate of new drug approvals worldwide for many indication in solid tumors actually is a reason for a lot of reasons, primarily depending on the budgetary problems, on the reimbursement problems, an the approval problems, is a reason for which most of the patients are still far behind the possibility of receiving them.

I think that this is a combination of so many factors, which we are still unprepared. But we should set in a position, or at least to learn how to be set in a near future, in order to deal with this problem and to improve, or to try to minimize as much as possible from our side this problem.

One of the issues, for example, in drug availability or in trial availability is the fact that most of the patient are unable to be evaluated in the molecular level with the test, commercial test, like the FoundationOne test. So are still unable also to be recognized as having a tumor characterized by certain molecular alteration that may allow them to receive some target therapy that is approved for this disease worldwide.

So this is a problem of drug availability, trial availability, molecular test availability. And of course, this is something that should be discussed at the multi stakeholder level. But we as investigators should try to sensitize as much as possible our collaborators, our partners, from the pharma companies and the payers and the healthcare system in general, to be involved in this endeavor. And to be open and to allow the inclusion of these patient to minimize this problem.

Ashish Kamat: Well said, Andrea. And again, thanks for taking the charge on this. In closing, let me just ask you to share with our audience... Because I speak for myself, but I've even discussed with the other people, we were really impressed at the retreat at the machinery that you have created for clinical trials and clinical studies at your institution in a short time.

So for those of our listeners that might be in the earlier stages of career, or are looking to start a research program at their new university, or new home, what are some pearls or pieces of advice that you would impart on them about how to create a successful research program, while of course being clinically busy?

Andrea Necchi: I would say the two main messages that I would deliver to young fellows and to people that are interested in investing their career in academic research and trying to be leaders, group leaders in a certain disease, is, number one, the possibility and investing a lot in trying to be able to launch and to be the primary investigator of an academic study. Investigator initiate study. With some budget of course.

Because the possibility of investing in a trial that is sponsored by your institution, and for which you have the full property of the data, and for which you have the full property of enriching the clinical data with biomarker data, biomarker research, may allow you, first, to acquire a lot of understanding and improve a lot of knowledge on a certain disease area. And second, to improve substantially the possibility for the visibility for you in terms of publication, in terms of presentation in congress. And being able also to allow fellow growing behind you on the same project.

So the availability of care of a trial sponsored by yourself. And I remember very well that the first trial that I sponsored was a trial with pazopanib in refractory urothelial cancer. The first trial when I was just specialized in medical oncology, I launched it as a primary investigator. And at the end it was published in 2012 in Lancet Oncology. And arised a lot of interest in anti-angiogenesis in this disease. Interest was not confirmed in other studies. Was one of the major steps in my career.

The second point from the organization point of view is the fact that you should consider that for establishing a trial machinery you need, first of all, people that are not MD, that are not physicians, but people that are specialist in trial conduct, so study coordinators, data managers and research nurses. These are the three main figures without which you are completely unable to run trials.

So in order to be able to be set in a good position, to be able to afford a decent number of trials, or in a growing number of trials, you should invest your budget in establishing a trial machinery that is mainly composed by study coordinators. This is one of the key for the success for your team in general, and for a research center in general. This is the one of the main goals for most of the cancer centers worldwide, without which the possibilities of being competitive in the trial landscape is very low.

Ashish Kamat: Yeah. I would just want to highlight that, because I completely agree. We'll see so many people, very, very well qualified, intelligent, driven investigators, try to do all of this without the appropriate support from their data coordinators, their statisticians, their resource nurses. And those people, I mean, they're part of the team and they're integral. Oftentimes they are more important for the successful conduct of the study to get patients enrolled than we are. And that's a very good point.

Andrea Necchi: So the other point that is a point that arise when looking at our internal organization, and the internal qualities in San Raffaele, was the fact that when considering, for example, the Department of Urology, that is worldwide organized as a leader in urological oncology, there is still a final step that is lacking. They're represented by the ability of running and promoting and sponsoring prospective clinical trials, and not just looking at high quality data from a retrospective dataset.

And I think that the availability of trials in early disease, like in bladder cancer, but also in the near future potentially more and more in prostate and in renal cancer, is instrumental also for us, as well as for many other investigators worldwide, to try to improve this lack of knowledge, especially from the urological side, in order to be able and to be fully prepared on understanding the needs for the qualities and the people that are required for running and for establishing a good trial machinery.

So again, the availability and the opportunities that come from the trial availability is substantial, and is completely shaping the way we are thinking and we are collaborating internally between departments.

Ashish Kamat: Once again, Andrea, thank you so much for taking the time. This was a great discussion. I'm sure our listeners and audience will really find that important. And the pearls that you mentioned are great. Looking forward to seeing you again, and also looking forward to the next retreat.

Andrea Necchi: Oh, great. You be the first people that I will invite, of course, and will be able and happy to share with UroToday the next edition. Thank you for your invitation.