When Exercise Is The Prescription

Alicia: This is the Good News About Cancer. My name is Dr. Alicia Morgans. 

Chuck: And I'm Dr. Chuck Ryan. 

Alicia: We're oncologists, and we've spent our careers working to understand cancer. We believe that there's more progress now in research and treatment than there ever has been, and we're here to share that with you. 

Chuck: In each episode of the show, we talk to one of our colleagues about a promising development in cancer. We'll break down what's new, why it matters, and how it points the way forward. 

Kerry: So this really makes, you know, exercise a win, if you will. You know, I refer to it as a grand slam. It improves overall survival, improves disease-free survival, it improves quality of life, and improves objective fitness and functioning. So, you know, it's a very powerful intervention for cancer patients.

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Chuck: So, Alicia, how was your summer? 

Alicia: It's been hot, but great. I mean, who doesn't love the summer? 

Chuck: Well, I remember, you know, when we did that great melanoma episode and you talked about how excited you were to get to the beach and all these things, and I just wonder, how did that work out for you? 

Alicia: Well, we didn't get to the beach, but you know what, we did go to the mountains, wore our sunblock, and did a lot of walking, hiking, climbing, all the stuff that you do when you're outside, really trying to get a little more exercise.

Chuck: So you get a lot of exercise. Uh, I suspect you're somebody who gets a fair amount of exercise in a routine week, even when you're not in the mountains. And we know that exercise has benefits for our general health. The challenge has always been that we don't always know what like the dose of exercise is, and exactly how to prescribe it. And that's because exercise science has a little bit lagged behind the development of drugs. 

Alicia: That's true. Not knowing how much, what type, or what the benefits might be of certain exercises is absolutely a challenge. But a new study tried to answer this question. 

So they asked: is there benefit when a certain amount and type of exercise is basically “prescribed” to cancer patients? And they were able to publish their findings in the New England Journal of Medicine to give us the first real data that we can use to think through exercise as a prescription for people with cancer.

Chuck: Yeah, so let's be clear. They did a study on patients with colorectal cancer who actually were undergoing standard therapy, having had surgery and chemotherapy. And then after they finished their chemotherapy, they underwent a randomization to coached exercise basically, or essentially recommendations but not coaching. And they found some really interesting results. 

Alicia: The study that we're talking about was led by Kerry Courneya. He is a professor of kinesiology at the University of Alberta in Edmonton, Canada, and he holds a Canada Research Chair in Physical Activity and Cancer. And we recently were able to talk to him about what makes exercise important and why a study like this was necessary.

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Alicia: Some people may wonder: why are we even doing this episode? Exercise is supposed to be good for everybody. Your doctor tells you to exercise. Everyone thinks that we should all be exercising. I should probably be exercising right now, but I'm here talking to you about how we learned that exercise is really a treatment for cancer, and we've proven that with this study. Tell me: why did we need to prove that? 

Kerry: So exercise has general health benefits for everybody, but what we look at in the field of excise oncology are cancer-specific benefits. Yes, we know it'll lower their cholesterol, it'll improve heart function, it will make them feel better and stuff. But what about cancer specific benefits?

And so these are things like chemotherapy completion, managing specific side effects for patients like fatigue, peripheral neuropathy, cognitive dysfunction, and so on. And of course, the biggest one of all is: is it going to manage the disease and not just the symptoms. So we asked the question: is exercise a treatment for stage three and high risk stage two colon cancer? And so that's a very important piece of information that we've now definitively been able to show. 

Chuck: So let's take a deeper dive into the actual data from your study that were published in the New England Journal of Medicine. I wonder if you could just start by walking us through these findings and what you think their implications are, and then we'll take it from there.

Kerry: So, I mean, the big news with this trial is it's the first randomized controlled trial to look at survival as the primary endpoint. So we've had a lot of observational studies suggesting that various cancer patient groups who exercise more after a diagnosis have a lower risk of recurrence and better survival.

But a lot of people are very skeptical of these observational studies because there's all sorts of explanations for why someone who's exercising might live longer than someone who's not. So, you know, there was definitely a need for the randomized controlled trial. And you know, the big finding of the study is what we showed is this three year structured exercise program that we developed improved disease-free survival in a meaningful way. In fact, it also improved overall survival. 

And I think some of the provocative discussion around social media was the magnitude of the benefits, suggesting it's performing as good as if not better than some of these, you know, key drugs and other biomedical treatments that we offer patients routinely. And so we feel like exercise, at least for the stage three, high risk stage two colon cancer, is now in this category of a treatment for cancer. It's not just a quality of life intervention in this patient group. It’s actually treating their cancer just as well as the chemotherapy and other treatments that we've tested over the years.

Alicia: So I just would love to hear you describe: what actually was this exercise? What did it look like? How was this structured exercise that was basically prescribed like a medicine to these patients, how was that different than just being active? 

Because I have a lot of patients in clinic who say, you know, I'm really active, I garden, I walk my dog. And these are fantastic ways for people to engage in their lives and be functionally fit. That's great. But in your study, there was a difference. It was a structured exercise program. So tell us about what that looks like so that we can understand kind of what these people did and over what period of time, for how long.

Kerry: So this study was on aerobic exercise or endurance exercise. We didn't intervene on strength exercise or nutrition or weight loss. It was strictly aerobic exercise. And we tried to get patients to increase from baseline as well. So this was a behavior change goal, not an absolute behavioral goal. We didn't say “achieve 150 minutes,” we said “add 150 minutes to what you're currently doing.” 

The big focus here is it had to be at least moderate in intensity, so it wasn't kind of the shuffling around in the garden or some of the casual walking the dog where you may have a coffee in your hand while you're walking the dog. All that, it's very good, as you said, Alicia, it's important activity, but we view it as light intensity activity. So we push for at least moderate intensity, which we describe to patients as at least brisk walking. You know, if somebody saw you walking, they would think you're late for an appointment. So we were pushing improvements in cardiovascular fitness because we know that's a very important mediator of these outcomes. 

And very importantly in our study, we got absolutely no weight loss. There was no difference between the groups and body weight or waist circumference. So this is not the explanation for exercise benefits. It's these improvements in cardiovascular fitness that come from doing an exercise of at least moderate intensity. And they could choose the frequency and they could choose the duration. And if interested, they could even up the intensity to some vigorous intensity or to some high intensity interval training. But I think that was the key ingredient, aerobic exercise of at least moderate intensity, and add two and a half hours per week to what you are currently doing. 

Chuck: I wonder if you could speak to the timing of when you started the exercise intervention. Many might be listening and they might be on chemotherapy now and should know when the exercise started, is it safe to do the exercise during chemotherapy or do we not really know that? And how do you reconcile those, those unknowns? 

Kerry: So in this study, we recruited colon cancer patients two to six months after they completed chemotherapy. So this is kind of a post-adjuvant or early survivorship trial. You know, you're done as far as we know with the treatments, and you're sort of the handshake at the door saying, “good luck with things. Hopefully it'll go well.” 

So we thought that was a really good opportunity to intervene because you know, as you guys know, newly diagnosed patients are going to be quite stressed, focusing on their treatments, their diagnosis, the implications. The chemotherapies can be tough, and certainly the chemotherapies for colon cancer can have some side effects.

So we felt that's a really good opportunity, when patients are ready. And that's the time patients are oftentimes asking, “what can I do for myself? You know, now that these treatments are done, what can I do to improve my own potential outcomes in terms of recurrence and survival?” So that's what we focused on.

Alicia: Yeah. You know, I wonder, Kerry, if you can try to help all of us understand the magnitude of this benefit. You know, how do you tell people that's really meaningful, or that matters? 

Kerry: Yeah. This is what makes exercise such a powerful intervention. For many of the drugs we give patients, quality of life is a trade-off to get the survival benefit. So we're oftentimes making patients sicker, having side effects. 

The side effects of exercise are all incredibly positive. We're improving physical functioning, we're improving quality of life. Evidence shows we improve sleep quality, reduce depression and anxiety rates. So this is why, again, many of the oncologists were saying, “this is actually even better than a drug because you're now proving a survival benefit. And then on top of that, showing some well-known quality of life benefits to exercise.”

And certainly in our trials, you know, we've had a number of patients tell us the psychological benefits of exercise are even more important to them than some of the physiological or even the medical benefits. They say, “exercise helps me feel normal. You know, everything about cancer is not normal, but when I'm out there doing my exercise, I'm kind of free from my cancer. I'm not thinking about it. And I feel like I'm doing well and leading a normal life.” 

So this really makes you know, exercise a win, if you will. You know, I refer to it as a grand slam. It improves overall survival, improves disease-free survival. It improves quality of life and improves objective fitness and functioning. So, you know, it's a very powerful intervention for cancer patients. 

Chuck: And those are the studies that get reported in the New England Journal of Medicine because they're grand slams and they change our thinking about a particular medical condition and they change our approach, which I think this certainly has.

Alicia: It's so exciting and I am so thrilled to hear this data from you and to really celebrate this opportunity. But I think one of the questions that I would have for my patients in clinic, and for the people I talk to, and maybe those listening is: do you expect that this amazing benefit that you saw in people with colorectal cancer who are going through all of this treatment, that this benefit might be something that somebody with breast cancer or leukemia or prostate cancer or lung cancer– that others might experience a similar benefit from this kind of a treatment, exercise as treatment?

Kerry: Yeah, I think that's the million dollar question, Alicia. Everyone wants to know how far can we generalize this to other patients, because of course these are very expensive trials, they take a long time to conduct. And so I think a couple possibilities. One is we have a number of cancers out there that we view as “exercise-sensitive cancers” based on preclinical models, where we show exercise slows tumor growth in various breast cancer cell lines, prostate cancer cell lines. 

And of course the observational data are quite strong in breast cancer and prostate cancer and even endometrial cancer. And what some people have pointed out is our demonstrated benefit was consistent with those observational studies. So perhaps then those observational studies are a reasonable estimate in breast cancer, prostate cancer, and endometrial cancer. So yes, I think there'll be some people who are willing to generalize the results to those patient groups where we have very good preclinical and observational studies. 

And the other reason we potentially think that is because the mechanisms we're proposing for this benefit are not colon cancer-specific. You know, exercise is not a targeted therapy where we think it's a particular receptor or a particular protein or molecule that we're targeting. Exercise has pleotropic effects, meaning all sorts of effects. 

And so we know that exercise has metabolic effects related to insulin and IGF levels, which promote tumor growth and spread. We know exercise improves immune function, natural killer cell counts and activity T-cell counts. We know based on immunotherapy, it's very important to have a good functioning immune system. Anti-inflammatory effects. So because of these broader mechanisms, I think it is reasonable to start thinking, well, maybe in some of these other cancers we should be able to generalize.

Chuck: I think it's a really critical point about, we don't really understand the one mechanism by which this works, but it's likely to work through many mechanisms. Which gets to, gets us to the point where exercise helps our body to know what to do to heal, in a way. And as scientists and oncologists, that's, you know, a little bit of hand waving, but it just speaks to the holistic benefits of exercise, as you point out.

The other thing that I was struck with in reading this, and thinking about this topic, is that it gives the patient agency. The patient has the opportunity to choose to do this. This is not a drug that needs an FDA approval. It is not dependent on the skill of a surgeon. It is something that every patient can look at and think, “Okay, I can try to do this.”

The question though, that arises in that setting is: How many patients found it very difficult to adhere to this program? Were there some patients who said, “I can't do it” and they dropped out? And what do you do for patients who in the midst of this intervention say, “I'm having trouble keeping up, or I don't think I can complete the program as you want me to.”

Kerry: Yeah, that's a really good point, Chuck. We do find exercise is an empowering intervention for patients. They love the fact that it's something they can do for themselves to help their own outcomes, and benefit from it. So that's part of the psychological benefit, I think, that these patients are able to experience, now knowing that they're actually improving survival outcomes I think will make it even more powerful.

You know, exercise, like immunotherapy and chemotherapy, I don't think every single patient can do this. I think most patients are able to do the intervention that we delivered, but some patients have significant mobility problems, significant deconditioning and functional impairments. Some patients are frail and to be fully honest, I think what we tested would not work for those patients. They would need a different type of exercise intervention, more based maybe on physiotherapy and low-level activities to try and get them functional. 

So, you know, the patients in our trial certainly were functional. In fact, they had to be able to walk on a treadmill, very slow pace, moderate pace, for six minutes. So I think that's important. But working with those patients, you know, we always work out wherever the patient's at, whatever they're able and willing to do, even small increases in exercise can be beneficial. And if not for the survival outcomes, for the functioning outcomes, for the quality of life outcomes. So we think all these patients can benefit, even from modest changes in exercise. 

Chuck: I wonder if you could just speak to your personal journey. You're a kinesiologist, if I know correctly, and you've spent your career studying the relationship of exercise to oncology, which this has to be one of the, if not the, highlight of that career building up to this. 

But it speaks to what we're seeing, which is a number of other disciplines coming into the cancer clinic, helping patients live better lives, live longer lives, by thinking through novel ways for us to approach the cancer problem. And so, you know, first of all, congratulations on being one of the world's leaders in this area, but just tell us a little bit about your personal journey, getting to this point.

Kerry: So my PhD was out of the University of Illinois at Urbana Champaign. So I was trained in the U.S. and really enjoyed my training there. And it was not an exercise in cancer, it was more on behavioral science types of things. And then my first position at the University of Calgary, in Alberta, is where I start getting interested in cancer. More just by chance.

Happen to meet some people who are studying exercise as prevention for cancer. So back in the nineties, the big focus of excise and lifestyle is whether or not you could lower the risk of incident cancer, getting cancer in the first place. Once you were diagnosed with cancer, we turned you over to the biomedical researchers and lifestyle didn't play a role.

So that's what was going on in Calgary in the nineties. But we started discussing what about on the post-diagnosis side? And so that's when I started my research program in the kind of early to mid nineties, and it really has evolved. Working with oncologists is fantastic, because they're the ones who push me to think about outcomes that are important to the patients, outcomes that are important to the oncologists.

And so I started really thinking more clinically, and that's how we started, first of all, in quality of life and symptom control. And then ultimately the oncologists were saying, “does this have any implications for survival?” And so it's been a great journey from small pilot feasibility studies to these multicenter trials to, uh, you're right, Chuck, I view this as kind of my career-defining accomplishment. This is a multinational large scale cooperative group trial showing benefits in survival. I think I can retire and feel good about that particular paper. I'm not retiring yet. We're going to do some more.

But it's been wonderful to have this journey and just to see how the patients respond. They're so grateful for this research. It's patients pushing for exercise research. It wasn't oncologists 20 or 30 years ago saying, “we gotta do this,” it's patients saying, “What about exercise? What's the role of exercise?” And they've been some of our biggest advocates and biggest supporters for the funding agencies to get the money to do this, but also for putting it into practice as well. So, yeah, a fantastic journey and there's more to come. 

Chuck: That's fantastic. 

Alicia: Wonderful. Well, I so appreciate you taking the time to talk about your work, but also talk about the way that the good news here is something that we can implement this afternoon if we want. At home, our patients can start exercising wherever they are and can start working towards these goals of really doing something physically, on their own, that ultimately will hopefully prevent some of their cancer recurrences, as well as make them feel well and make their lives better at the same time. I've so appreciated talking with you. Thank you so much, Kerry. 

Kerry: Thank you for having me.

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Alicia: Really love the way we were able to talk with him about the way that people can start from wherever they are beginning, and just do a little more exercise, a little more physical activity, something that works for them, for their body, for their ability, and make such a positive difference. 

Chuck: A hundred percent. The headlines here, I think there's two. One is: Exercise reduces mortality in patients with colorectal cancer, big headline. The second is that: there are things you can do if you are a patient, you have agency, you have some control over what you can do, and it's part of a bigger story that's being told now about activity levels and exercise, all kinds of areas of health and wellness.

Exercise in this setting reduces the risk of colorectal cancer. But exercise, even in the form of just taking multiple daily steps, cardiovascular mortality, the risk of dementia, the risk of falls, the risk of diabetes, all of these things get better with exercise, and this is something that every one of us out there has control of in our daily lives.

Alicia: And the other piece that I think is important to remember is that movement is really something that helps not just physically, but with our mental health. And when it comes to cancer, and when it comes to being optimistic and having hope and thinking about the future, and tomorrow, it's really, really important to make sure that our minds are in the right place just as well as our bodies are in the right place.

Chuck: I would propose to you that we are going to be hearing a lot more good news about the role of exercise in cancer treatment, cancer prevention, and the lives of people affected by cancer in general.

Alicia: Thanks for listening to the Good News About Cancer. I'm Dr. Alicia Morgans, at Dana-Farber Cancer Institute in Boston. 

Chuck: And I'm Dr. Chuck Ryan at Memorial Sloan Kettering Cancer Center in New York. The views we express on this show are our own and do not represent the views or opinions of the institutions where we work.

Alicia: Thanks to Lilly for support of the show. Our production partner for this series is CitizenRacecar. This episode was produced by Anna Van Dine with post-production by Alex Brouwer. 

Chuck: And as usual, there's a whole lot more good news to talk about. So make sure you subscribe to this wherever you listen to your podcasts.

And if you like the show, share it with someone you think might find it interesting. And if you don't like the show, share it anyway, because they probably will. 

Alicia: We'll be back again soon with more good news about cancer.