Charles Ryan: Hello from PCF 2019. I'm delighted to be joined by Dr. Stacey Kenfield, a colleague from UCSF where she is an Associate Professor in the Department of Urology and is the Helen Diller Family Professor of Population Science for Urologic Cancer. And you are an expert on lifestyle, exercise, nutrition and their impact on prostate cancer. This is a really important issue for patients and so many of them and those of us who treat them are hungry for information. Tell us about your work that you've recently completed and are continuing on the Prostate 8 program.

Stacey Kenfield: Sure. So the Prostate 8 program started a couple of years ago. It was based on a lot of observational work that I've done with other people, both at Harvard School of Public Health and UCSF. And we looked at men with prostate cancer and studied different dietary and lifestyle factors that might be associated with prostate cancer progression. So we looked at both PSA progression as well as dying of prostate cancer in these two different cohorts of men. And what we found is that there are specific dietary and lifestyle factors that are important. So, for example, we found that cruciferous vegetables are important for preventing prostate cancer progression.

Charles Ryan: So broccoli, cauliflower, kale, arugula...

Stacey Kenfield: Arugula, watercress, things like that. And then on the exercise side, we found that vigorous activity is actually quite beneficial. The first paper that came out was in 2011 in the health professionals follow-up study. There, we found that three or more hours of vigorous activity was associated with a 61% lower risk of dying of prostate cancer. And that was a huge finding and really surprising that it was so strong.

Charles Ryan: That was in men who had been diagnosed with prostate cancer. And you looked at the exercise intensity after the diagnosis and their risk of dying of the disease. Just to be clear.

Stacey Kenfield: Exactly. And so that was done in the health professionals follow-up study. At the same time we looked at this association in the capture cohort. There weren't enough people exercising vigorously there. So we looked at brisk walking and what we found was that people that were walking briskly, three or more hours a week, had a 57% lower risk of prostate cancer progression. And since then, in 2017 and 18, there have been other cohorts that have been publishing of men with localized or even advanced prostate cancer. Finding that some walking or vigorous activity is beneficial. So you can possibly see a benefit even at four and a half hours of walking or a couple of hours of vigorous activity. What's critical is that you do something. So if you're not doing anything now, I suggest you start slowly and build up to levels that you can obtain.

Charles Ryan: And you and I have worked together on the development of two clinical trials that integrate exercise and they're testing a couple of different things, resistance and aerobic. As you're using the word intense exercise, I'm sure a lot of people are saying, well what does she mean? How do I know what I'm doing is intense? So tell us how to parse out those issues. What's intensity and should it be aerobic or should it be resistance?

Stacey Kenfield: I think both of them are critical. So I think you need to do aerobic activity for your cardio-respiratory fitness and then also resistance train to maintain your bone and muscle mass. And so the study that we're doing together incorporates looking at those two types separately in men with metastatic castrate-resistant prostate cancer. The study that we are also doing globally looks at a three day per week program combining both moderate-continuous and high-intensity interval training as well as two days a week of resistance training for the same population, men with metastatic castrate-resistant prostate cancer. And as you know it's now at 16 sites in seven countries and we're really excited to see that continue to grow and enroll.

Charles Ryan: Yes, that's the gap for the interval studies sponsored by Movember. We have other interviews on the site around that study and it is accruing patients and it's for patients with metastatic castration-resistant prostate cancer and now hormone-sensitive metastatic disease as well. So anybody who's really on hormonal therapy could be eligible for that study. Okay. So tell us a little bit about the algorithm that you did, Prostate 8, and how you are hoping that this can help patients to modify their behaviors around exercise and nutrition. And I guess I should just start with the question is how hard is it to modify behavior in a 60 or 70-year-old gentleman?

Stacey Kenfield: Right. So we took eight of those factors, as you said, that we found to be beneficial for reducing risk of prostate cancer progression or mortality and we put them into a study. We randomized people who were doing four or less of those factors at baseline and we asked them to try and change their behaviors over the course of 12 weeks. The study was randomized, so half of the patients received the intervention, which was a web-based intervention that included text messaging as well as a Fitbit. And then there was a control arm. And what we found in those 12 weeks was that people were able to change aspects of their diet. So we saw an increase in cruciferous vegetables, an increase in cooked tomatoes, an increase in fish, and a decrease in processed meat over that course of 12 weeks. Which was really exciting to see that we can give men information and tools to help them make changes to their lifestyle.

Charles Ryan: These are men on with localized disease on active surveillance.

Stacey Kenfield: Or radical prostatectomy.

Charles Ryan: Okay. And just to be clear, it's called Prostate 8 because there are eight elements?

Stacey Kenfield: Yes. Oh, cruciferous vegetables, cooked tomatoes, fish, low processed meat, non-smoking, not taking supplements unless recommended by your physician to do so, vigorous activity and healthy fats. So eating avocados, olive oil, nuts, things like that.

Charles Ryan: And low processed meats means eat relatively few processed meats like bacon and sausage and those types of things. Okay. All right. Yeah. And so what's your plan with Prostate 8?

Stacey Kenfield: So Prostate 8 has evolved now. So there's a Prostate 8 II, and we're randomizing 200 men to a diet only arm, an exercise only arm, a combined arm, and a control group. And we are looking more at the mechanisms, the biological mechanisms behind the associations to learn more about that. As well as to see if men can maintain these behaviors over the course of two years. So it's a much longer study and that's unknown right now whether or not maintenance can occur once you learn this information,

Charles Ryan: Do you get feedback from the patients on how valuable the persistence of the messaging is? You said they get a text message that says something like 'eat salmon' or something like that. And, they may come in for a session and learn all of this at the beginning, but is it the persistence of the messaging that's helpful for them?

Stacey Kenfield: Yeah, so we did do some acceptability work in the first study and we did find that men enjoyed being contacted. They liked the communication with the study staff. So that's helpful. This time around, we're also adding tracking and giving some awards for tracking and meeting goals. So it's a little bit more advanced at this point. And we're also sending out more personalized messages. So if you're not meeting a goal one week, we'll try to encourage you to do so in the next week. So there's a little bit more personalization, which I think really helps.

Charles Ryan: Right. Personalization and persistence, which is probably the key to that as well. So this is really great because you're building on epidemiological data collected over decades and then turning it into a prospective intervention using new technology. And it's highly popular, I think, for patients who want to do this. As I said, as a clinician, this is one of the top questions I get. What should I be eating? What should I be doing? And I always cite your data when I'm talking to them in terms of, we think this is what is the right thing to do. And I always mention Prostate 8 and then I go through all of the eight things and try to remember all of them, which is really good. So, congratulations. A lot of really amazing prospective work being done around the world based on your work. And it's great to be a part of it. And thank you for sitting down with us.

Stacey Kenfield: Yeah, of course. Thank you.