Phillip J. Koo: Hi. I'm Phillip Koo, and welcome to UroToday's exclusive coverage of the 13th International Uro-Oncology Congress here in São Paulo, Brazil. We have with us today Dr. Laurence Klotz, who's professor of urology and Sunnybrook Chair of Prostate Cancer Research at the University of Toronto. Welcome.

Laurence Klotz: Thanks very much.

Phillip J. Koo: So, Laurie, you've been to Brazil several times.

Laurence Klotz: I have indeed.

Phillip J. Koo: Before we start getting into some of the science, give me Laurence's best of Brazil.

Laurence Klotz: Well, that's easy. It's a huge country. It's a multifaceted country. And I've had the opportunity through a lot of my trips here to travel really quite a lot through the country. I would have to say my favorite location in Brazil is the island Fernando de Noronha, which is a little island about 250 miles east of the northeastern coast of Brazil. It's the eastern most point of the Western hemisphere. And it's like Treasure Island, this unspoiled island. And we went there, a group of us, including some Brazilian colleagues, after meeting a few years ago and just three days of paradise.

And then the other place that really is so special is the Amazon and up around Manous. We had a trip with Fernando de Maluf and my wife up the Amazon. We stayed in a hotel floating on barrels, floating on an estuary off the Amazon. And it's like a trip back in time. There's still tribes there living in a very unspoiled traditional way. And just to see that was remarkable. Swim with the dolphins, see just a part of the world that is so foreign compared to the usual. And many other really remarkable places in this country. So, I love visiting here. It's a very special place to come to.

Phillip J. Koo: Great. So, if you're planning a trip to Brazil, give him a call or an email and he'll have some tips. All right. So, we're going to start off obviously talking about active surveillance. A hot topic. Clearly there are challenges with active surveillance in developing countries that might not have a formal prostate cancer screening program, that might not have the resources, that might have certain cultural challenges with regards to implementation. What advice do you have for those people who are thinking about this?

Laurence Klotz: Yeah. So, many facets to that question. So, my sense going around the world talking about this is what you say is really true, that there are cultural differences, probably related to education and also to the perception of what the word cancer means and implies for people. And I know in my world when this whole thing started, say roughly 20, 25 years ago, to tell a patient he had cancer but he didn't need any treatment, it was a real conundrum for the patient. Like, "What is this guy talking about? This is cancer. I have to do something." And there's been an evolution in, I would say, the developed world, I'm talking about mainly the United States, Canada, Western Europe, where there's a much broader understanding amongst non-medical people that there is such a thing as indolent cancer, the concept of over-diagnosis. People now, they've heard about that.

They've read about it. So, now when you tell a patient in my practice, "Yes, you've been diagnosed with this cancer, but it's really not anything you need to have treated or worry about," that has a much more receptive response than it used to. And my sense is in many countries in the world the population is still back where it was 25 years ago in North America, which is that this is still news that there's such a thing as an indolent cancer that doesn't need to be treated. So, part of it is a broad education and part of it is the challenge, which is not that difficult, in my opinion, of communicating to a patient the significance of what they have. And I use words like pseudo-cancer, part of the aging process, zero risk of metastasizing. You say three phrases like that to the patient, you can see them visibly relax. And they turn to their wife and they say, "What have we been so worried about?" So, I think how you communicate, using the right phrases, educating the patient is really critical.

The second point, I think, is that the practitioners actually have to believe in this concept. And initially there was some pushback in North America and Europe. Obviously, not treating patients, if you're a guy who earns his living operating or radiating prostate cancer, this potentially is threatening. But that has changed completely, I would say. Almost completely. There's no pushback on the concept anymore. But I think one of the issues here is that once a patient's been diagnosed with cancer, they are really putty in the hands of the physician. And all the physician has to say is, "Well, yes, there is this conservative management, but you never know. And there is some risk." And bingo, the patient ends up with a probably unnecessary treatment. So, I think it behooves practitioners to at least satisfy themselves that this concept is robust. It's a good thing to offer patients.

In fact, modeling has shown that from a pure business of medicine perspective, following a patient for many years doing periodic biopsies probably generates as much income as doing a radical prostatectomy on the patient. So, I think from a pure volume of practice perspective, there should be no resistance to it at all. And of course, what should drive medical practice is the patient and the patient's health and welfare. And I'll just make one other point about this. Early on people said to me, "You're never going to change this. You're never going to get American urologists to stop operating." And I came to the conclusion that I would say almost 100% of our colleagues, I think around the world, they want to make a living, but they want make a living doing the right thing. And there's very, very few practitioners who really want to make a living doing the wrong thing.

It's where you have a gray zone, where you have options that provider preference and economic incentives and financial drivers really come into it. So, the way I framed this whole thing in my mind was, shrink the gray zone. And I think that's happened. So, all the groups that develop guidelines now say, for grade group 1 prostate cancer, active surveillance. And therefore it's become more difficult, as it should be, for practitioners to, in their own mind, say, "Well, I just don't believe in that and we're going to treat this patient radically." So, there's got to be change in terms of patient education and in terms of practitioner perspective.

Phillip J. Koo: That's great. Clearly the data's there. The guidelines now are reflecting this important change. And perhaps in these developing countries, it's just we got to keep fighting the good fight and people like you who really pioneer this will be able to impact this community, I guess, over time. So, shifting gears a little to HIFU now. So, similar perspective here. A new technology, a new way to treat prostate cancer. Still some controversy over that, especially in certain countries that aren't as comfortable with this or have done this as long. It seems like it's gaining some foothold here in Brazil. What recommendations regarding challenges and opportunities do you have for Brazil and other Latin American countries?

Laurence Klotz: Yeah. So, my experience is, first of all, when you start doing this and you see these patients who are treated with some kind of focal therapy and they're cured, and they have essentially no quality of life effects, and it's very hard to see these patients and not say, "Wow, this really has value." The challenge, of course, is to pick the right patient, to pick up the failures early so they're still amenable to salvage therapy, to not over-treat patients who don't need treatment, not under-treat patients who have more advanced disease than really is amenable to focal therapy. So, there's a lot of issues around focal therapy and that may be why there's been a lot of pushback. My sense is where this is ramping up, a lot of it is patient-driven. Someone tells them they need a radical prostatectomy, and they hear about a guy who had HIFU or some other form of focal therapy and was cured and had no side effects.

I also think, at least in North America, my sense is radical prostatectomy has been done on so many people. Everyone knows someone who's had this operation now, and they know about the risks of incontinence and erectile dysfunction. And I believe there's a lot of apprehension out there, it may not be stated, but a lot of apprehension when you tell someone they have to have a radical prostatectomy. This is falling in a way on ground, they already have some preconceptions about this. So, you give them an alternative, boy, they grab it. And I think to start out the thing is to pick patients who really are ideal patients, which is the patient with a grade group 2 cancer and a single lesion seen on MRI and systematic biopsies don't show any other disease. And the data is pretty solid in those patients.

They have roughly 85% chance of getting the treatment and not requiring anything further. And I think over time as one gets more experience, you can start to expand the indications. And then the other question. I mean, you mentioned HIFU. There's at least five or six competing technologies. I don't know which one is going to be the winner. There may not be one single winner because what happens in an area like this is you get people develop a lot of expertise and comfort with one technology. And even if you had, let's say, you had a phase three randomized study comparing cryo to HIFU that showed some small benefit with one over the other, the guy who's spent his career doing cryo and is really an expert at that and gets good results is not going to stop doing it. And vice versa. So, I think this is a major area for studies over the next 20 years or so to try and sort out which technology is best for which patient. And ultimately there may be a few of them that coexist and you just have advocates for one or the other.

There's also these new technologies, these MR thermometry-based technologies like TULSA, which I've been involved with, the insight technology that I think may represent the next generation involving greater precision. Ultimately it'll come down to, I think, which technology offers the greatest precision on one hand and also, which is the most efficient, least costly, easiest to offer in terms of the infrastructure that's required. So, there's a lot of factors that are going to come into which one is the preferred one. And I'm not even sure it matters that much because for most of the patients you're treating beyond the actual lesion. So, does it matter whether one offers precision of a millimeter or two versus three or four millimeters? I don't know. Time will tell.

Phillip J. Koo: Time will tell.

Laurence Klotz: But I think this is really an emerging area. There's this new Focal Therapy Society based in the United States, but it's intended to be a global society. Studies are ramping up. It's a very exciting area to be in. And I would really encourage, particularly young practitioners, to get involved in this because there is so much work to do to establish some basic principles. We're really at the beginning of this.

Phillip J. Koo: One thing I've learned in this trip is I think Brazil is actually positioned really well to be a leader in focal therapy. They have great prostate MR tools and resources. And it seems like culturally, erectile dysfunction is a bigger concern in the community. So, that might lead patients to seek something like this a little sooner.

Laurence Klotz: Yeah. Well, I mean, I would say one incontrovertible fact is if you preserve prostate tissue, you preserve function. And there's really no question. There's a lot of unanswered questions in this area, but the fact that you have better preservation of erectile function and continence with focal therapy, we know that's true. So, yeah, I think where you have a population that's very focused on erectile function, it's very appealing.

Phillip J. Koo: That's great. Well, thank you very much. It's always so enlightening. And I think this provides a lot of hope and inspiration for the people of Latin America to really seize these opportunities. So, thank you.

Laurence Klotz: Pleasure.