Conversations With Prostate Cancer Experts

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Exercise Interventions For Men With Prostate Cancer

Winters-Stone headshot

Dr. Kerri Winters-Stone, an exercise scientist and Professor in the School of Nursing at the Oregon Health & Science University (OHSU), is the Co-Director of the OHSU Knight Cancer Institute’s Community Partnership Program and Co-Leader of the OHSU Knight Cancer Institute’s Cancer Prevention and Control Program. She is keenly interested in how physical activity can help us prevent and manage chronic diseases and specifically cancer.

Prostatepedia spoke with her about a clinical trial she’s running in conjunction with Movember that looks at how to deliver physical and nutrition advice to men with prostate cancer using digital technology.

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How did you come to study physical activity in cancer survivors? What path led you to where you are now?

Dr. Winters-Stone: I’m trained as an exercise scientist with a focus in skeletal physiology, so my original research was aimed at figuring out how we use exercise as a way to prevent osteoporosis and osteoporosis-related fractures in later life, around primary prevention. My research had little to do with cancer, and then I ended up collaborating with an oncology nurse scientist who was a cancer survivor and also a researcher. She was interested in using exercise for cancer symptom management, around acute symptoms when people were undergoing treatment, but at the time, research was identifying more of the long-term late effects of many cancer treatments, such as bone fractures.

In particular, we focused on breast and prostate cancer, and as men and women were being studied for longer periods of time, there was an increasing recognition that bone fractures were now among the many side effects that those cancer patients may experience. So this investigator and I ended up collaborating together because I brought my expertise in osteoporosis prevention into the cancer setting.

We were able, at first, to take the exercise programs and prescriptions that we knew were effective at preventing osteoporosis-related fractures in the general population, which is mainly in women, and see whether or not they would be as effective in preventing fractures associated with cancer treatment.

Interesting. Usually you hear a mentor bringing someone in, but not a colleague.

Dr. Winters-Stone: She became a mentor. I was completely new to cancer, so she taught me a lot.

Why is it important for prostate cancer patients or survivors to think about diet and exercise?

Dr. Winters-Stone: Diet and exercise are important for everybody, right? The new physical activity guidelines for all Americas were released today. They highlight the importance of physical activity for chronic disease prevention, including cancers but also as chronic disease management. One of the things that makes exercise particularly compelling for people with cancer is its ability to help manage adverse effects of not just the illness but also the treatments that accompany the illness. Over the last twenty years, we’ve learned the ways that staying active and moving can help prevent some of the acute symptoms, the GI distress, the fatigue, and the sleep problems that people get when they go through treatment.

Exercise is wonderful because it affects both physical and mental health. It can also help address some of the mental health changes that happen when someone gets a cancer diagnosis, by reducing anxiety and depression. It can be helpful in the short term, so that’s just helping you cope with treatment.

People also tend to decondition over a treatment period, so even if they’re not regularly exercising, they become even more inactive and sedentary. That impacts their day-to-day functioning. When someone is trying to recover from illness, now they’re more detrained from their day-to day-life, and it can be hard to do things like go back to being independent, taking care of yourself, going back to work, and taking care of children. Regular activity can help buffer the deconditioning that happens with treatment.

There’s more and more exciting evidence that suggests that exercise may even play a role in changing the course of the disease. There may be a good reason to view regular physical activity in terms of adding another component to a person’s long-term care. This is something that patients can do for themselves in terms of their prognosis. They can stay active and manage their weight.

Multiple reasons.

Dr. Winters-Stone: There are many reasons. Everybody should do it. It’s particularly important for people who are going through a chronic illness. In the case of cancer, people are usually older and experiencing some declines due to aging, so there’s yet another reason to exercise.

Can you tell us about the trial that you’re running in partnership with Movember?

Dr. Winters-Stone: This is a project that came about as part of an initiative from Movember that was aimed to develop novel and scalable approaches to addressing the problems that men face the most in survivorship.

One of those identified problems was around maintaining a healthful lifestyle. We already know, from well-controlled trials, that a healthy diet, managing weight, and getting enough exercise has benefits for men with prostate cancer, but we’ve not been effective at translating that information into action.

The number of men who still report unhealthy diets and low levels of physical activity remains high even though this information is available. There’s an implementation problem or a dissemination problem. We’re either not getting the information out there, or men are getting the information, but they don’t know how to act on it.

Part of this initiative for Movember seeks to ensure that interventions are scalable to as many men as possible so that access isn’t as much of an issue. Movember required that any interventions or programs be deliverable online or through technology.

In addition to our exercise expertise, we’ve teamed up with my colleagues at University of California, San Francisco (UCSF), who are experts in diet and prostate cancer progression, to develop a web-based diet and exercise intervention program. There are a lot more eHealth and mHealth types of interventions that give everyone a Fitbit and expect people to completely overhaul their lifestyle. But we still don’t know what are the magic ingredients that will translate information into action and change.

Besides developing a way to deliver that information online so it can get to any man anywhere, as part of the study design, we wanted to know how much and what kind of information and support men need for this program to be effective.

There are levels of intervention components that are part of the study design. They go from a low dose and low touch, which provides readable information on the internet, to increasing levels of interactivity.

The next level is to customize a diet and exercise plan for each man. We’re not just going to tell you to go get active; we’re going to tell you what to do with actionable information that’s going to be based on what you tell us about yourself. In effect, we digitize an exercise and diet planner for you.

In case that may not be enough, the next level adds low-cost tech-based motivational tools, like text messaging and a Fitbit, which don’t necessarily require a live professional, but which may add the motivation that someone needs.

Some may need some human contact to put this all in context, so the fourth level includes all of what I’ve said before plus access to a health coach. They get a phone call, a consult, and ongoing advice. We’re trying to understand how effective these different approaches are at improving men’s physical activity levels and dietary habits, with an eye for scalability. You want the most scalable, low-cost yet effective combination. Once Movember gets the results of all of these different interventions that are applied for different outcomes, they will have a web-based suite of support tools and services for men with prostate cancer.

Are you enrolling already?

Dr. Winters-Stone: This trial aimed to enroll 200 participants, and we have enrolled 206. We’re currently following all of these men. They get exposure to the website, whatever level of support they’ve been assigned to, for three months, and we assess them before they get into the website, after three months, and then again three months later.

At that point, will you be reporting out?

Dr. Winters-Stone: Yes. We should have the last man exited with his six-month follow-up in March of 2019.

Right now we can’t yet report on any study results, but we should have an article on the study published in late 2019. But already we’ve heard a few men say, “this has been so helpful,” or “I’ve lost three pounds already.” It’s nice to see at least some individual success stories.

Are there other similar trials that you’ll be running?

Dr. Winters-Stone: This is the only trial that I’m involved with that is completely online, which is more of a distance-based approach than what we usually do. We run a lot of supervised exercise trials, where men come to a facility to exercise, but we also know that not all men may be able to participate in supervised group exercise programs so finding ways to get information out to men regardless of their access to professionals or facilities is important.

Right. Are all of the participants close by, or because it’s web-based, does it matter where they’re located?

Dr. Winters-Stone: They’re all over the country. We have three recruitment sites.

At Oregon Health & Science University (OHSU), we’ve used a hospital registry, so because we’re a tertiary care center, we get guys from all over the state and some neighboring states. We’re trying to capture some of the men who live in more rural locations because that’s typical of our Oregon population.

UCSF recruited through a large epidemiologic study that they have been running, so we have men through who live all across the country. Because their outreach is across the United States, hopefully we’ll get better socioeconomic and racial representation.

And then UC Denver is the other participating site, so we’ve got a lot of men around Colorado. They’re trying to enroll more Latino men because those individuals are in their demographic and we need to ensure that our program can work for men with prostate cancer regardless of race/ethnicity or geography.

Any comments for men about the trial that you’re running or about the idea of this remote monitoring of patients in terms of exercise and diet?

Dr. Winters-Stone: The charge is on the medical and fitness communities to make sure that when men get diagnosed with prostate cancer, they get a recommendation to aim for a healthy lifestyle. There’s probably not an audience member of yours who doesn’t think he should exercise, but he may not know what to do and have trouble getting started.

Well, there’s thinking you should do it and then actually doing it.

Dr. Winters-Stone: Yes, and I’ve heard from so many men that motivation is the barrier. They are knowledgeable, and they know exercise is something that they should do, but they struggle to find the mental and physical motivation to do it. That could be because a lot of the men who I talk to have advanced cancer, and their treatments are just very fatiguing.

So my advice is—and this is out in the new physical activity recommendations—that something is better than nothing. To start, sit less and move more. That is the first step in behavior change.

Even though we have targets and recommendations, the first step is small, especially if that’s where someone is, simply dealing with getting off the couch. Interjecting short periods of standing or some movement for short periods of time would be a good first goal.

The next thing I would say is figure out what motivates you, and enlist that tool. It may be a buddy. It may be your wife or partner. It may be being accountable to somebody. It may be writing down your goals or writing down what you eat. That tends to be very effective.

I’ve known a lot of people who have signed up for My Fitness Pal and lose weight because they had to write things down. Apple Watches and Fitbits can be good in the short term to get someone moving more. Trying to figure out the one thing that might help get you motivated and then taking some action on that.

That’s actually great advice because often we don’t know what motivates us and what doesn’t. You can choose to include that in your life or not, right?

Dr. Winters-Stone: Yes, you can avoid it. It’s like it doesn’t happen, but once you start writing down what you eat, all of a sudden, you have to face the fact that you snack a lot.


Dr. Winters-Stone: Another thing that we have found can be helpful is to try not to go it alone. Loved ones are often asking what they can do to help someone diagnosed with cancer. Maybe they can go for a walk with you.

It’s a positive thing they can do.

Dr. Winters-Stone: It’s good for everybody, and it gives people the time and space to breathe, think about something else, and have good conversation. So maybe that’s the message to give caregivers, friends and family. Instead of asking what you can do, ask to go for a walk.

Then you get the exercise and the socialization too.

Dr. Winters-Stone: Yes. There’s a video a good friend of mine just showed me called Phil’s Camino. It’s about a man with cancer who used walking as his therapy and as his way to come to terms with his cancer. I highly recommend it.

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Exercise Recommendations For Prostate Cancer Patients

Robert Newton Headshot 2018Professor Rob Newton is the Associate Dean of Medical and Exercise Sciences and the Co-Director of the Exercise Medicine Research Institute, School of Medical and Health Sciences at Edith Cowan University in Perth, Australia.

Dr. Newton offers exercise recommendations for men with prostate cancer.

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Have you had any patients whose cases have changed the way you view your role as a clinician or how you approach talking about exercise with prostate cancer patients?

Dr. Robert Newton: Definitely. One fellow in particular had never exercised since he was a young boy, was quite overweight, and had very low fitness. When diagnosed with prostate cancer his urologist told him, “Don’t worry about having cancer, because you are going to die of a heart attack long before your prostate causes you problems.” I worked with the dietician in our team to develop a very low caloric diet and a relatively high volume exercise program for him. He lost 21 kg of fat in eight weeks. The transformation in his health and fitness was phenomenal. His urologist could not believe the change and commented that the prostatectomy was much easier and more successful than he expected.

This, and many other experiences supporting men with prostate cancer, has convinced me of the massive difference that an appropriate exercise prescription can have for these patients. We can definitely improve their outcomes.

What do we know about the impact of exercise on prostate cancer progression? What do we know about the impact exercise can have on how men with prostate cancer withstand specific treatments—surgery, radiation, hormonal therapy, etc?

Dr. Newton: As yet, there is not definitive clinical trial evidence of the impact of exercise on prostate cancer progression. We are currently running a world first trial in men with localized disease specifically to address this question.

However, preclinical experiments involving prostate cancer cell lines have demonstrated up to 30% suppression of growth. There are now several animal studies demonstrating similar cancer suppression. What is more clearly supported by multiple human trials is that specific exercise reduces complications and side-effects of surgery and various treatments and may also actually enhance the effectiveness of radiation therapy and chemotherapy.

For example, work from our team has shown that exercise leading up to prostatectomy surgery results in less incontinence and much better fitness and health.

There is less evidence with regard to exercise improving tolerance of radiation therapy, however, there are strong theoretical mechanisms by which exercise performed immediately prior to a radiation therapy session may actually enhance the effectiveness of the radiation, resulting in greater cancer cell death. This occurs by increasing blood flow through the tumor, facilitating the oxygen enhancement effect of the radiation.

By far, the strongest evidence as to the benefit of exercise is for men on ADT for their prostate cancer. There are now many large randomized controlled trials clearly proving that exercise reduces the toxicities of ADT. In particular, exercise slows or prevents muscle and bone loss and limits the onset of metabolic diseases such as diabetes and cardiovascular disease, which are common side effects of ADT.

Do you suggest men with prostate cancer see a trainer to help them set up an exercise program?

Dr. Newton: Ideally, men with prostate cancer would seek the assistance of a qualified exercise professional, such as a clinical exercise physiologist. These allied health professionals are university trained and have specific knowledge and skills in exercise assessment and prescription for people with chronic diseases like cancer. I do recommend that patients go through this process to ensure that they have an optimal exercise prescription that addresses the morbidities and risk of mortality in a prioritized strategy. This means designing an exercise prescription tailored for the individual and the problems that they are experiencing.

What type of exercise program do you recommend for men on Active Surveillance?

Dr. Newton: Unless there are other comorbidities and provided that the men are relatively healthy, then my recommendation would be for them to try and meet the American College of Sports Medicine guidelines for healthy older adults: 75 to 150 minutes per week of moderate to vigorous aerobic exercise and two or more resistance training sessions exercising all of the major muscle groups. This does not really need the input of a qualified exercise professional, but could be pursued under self-management or in a local fitness center.

What type of exercise program do you recommend for men on ADT?

Dr. Newton: Men on ADT may experience considerable toxicities, which impact their physical structure and function as well as greatly increase the risk of chronic diseases such as diabetes and cardiovascular disease. These men really need a tailored exercise prescription that targets the health issues causing them the greatest morbidity. For example, loss of muscle mass is a major problem for men on ADT. It requires a highly specific program of resistance training involving higher volume (or dosage) combined with a protein intake of at least 1.6 g per kilogram body weight per day. Maintaining muscle mass in these men is very important because it is a strong predictor of cancer recurrence and mortality.

Another ADT side-effect is bone loss which places the patient at considerable risk of skeletal fracture. In this instance, a highly specific exercise prescription incorporating resistance training and special impact loading consisting of skipping, jumping, and hopping is recommended as recent research has demonstrated that other forms of exercise have absolutely no benefit in terms of ameliorating the bone loss. However, such programs are highly advanced and must be closely monitored requiring supervision by a qualified exercise professional.

What type of exercise program do you recommend for men after surgery?

Dr. Newton: Post surgery, the patient will be considerably deconditioned in terms of muscle and strength loss and reduced cardiorespiratory fitness. They may also have some surgical complications, the most common of which is urinary incontinence. Exercise should be commenced as soon as possible after surgery to reduce further decline, albeit at a relatively modest dosage of aerobic and resistance training. As the patient recovers from surgery, exercise volume and intensity should be increased as tolerated. In particular, if urinary incontinence is experienced then targeted exercise prescription including pelvic floor exercises as well as exercises for the large muscle groups around the pelvis should be included. Just because a man has urinary incontinence, he should not avoid exercise and must perform resistance training even if he experiences some leakage. Resistance training has been demonstrated to enhance recovery of continence.

What type of exercise program do you recommend for men on radiation therapy?

Dr. Newton: Patients should continue to exercise throughout the course of radiation therapy even when experiencing treatment-related fatigue. If fatigue is a major problem, than the volume of exercise should be reduced and the intensity increased with a greater emphasis placed on resistance training and a reduced volume in particular of aerobic exercise of low intensity. In our clinic, we provide a specific exercise program of 10 to 20 minutes incorporating aerobic exercise and resistance training of the muscles of the pelvic area (e.g. squat, lunge, step-up) advising the patient to complete this program immediately before they enter the room to receive the radiation therapy. As noted above, there is emerging evidence that this strategy may greatly increase the effectiveness of radiation therapy to destroy cancer cells.

What type of exercise program do you recommend for men on chemotherapy?

Dr. Newton: Patients should exercise throughout the course of chemotherapy, however this should be auto-regulated. What this means is that the intensity and volume of exercise in a given session is adjusted up or down depending on how the patient feels on that particular day. The exercise program should be designed specifically to address key health issues facing the patient in a priority order.

Similar to radiation therapy, there is good evidence that performing a short exercise bout immediately before receiving chemotherapy may enhance its effectiveness by increasing blood flow through the tumor, thereby delivering more of the drug. It appears that there is a strong relationship between chemotherapy tolerance/side effects and the muscle mass of the patient. Patients with low muscle mass experience more chemotherapy side effects and are more likely to require a dose reduction. Receiving less than the plan dose of chemotherapy reduces overall effectiveness.

What type of exercise program do you recommend for men on drugs like Xtandi (enzalutamide), Zytiga (abiraterone), Erleada (apalutamide) or even Xofigo (radium-223)?

Dr. Newton: We are currently leading an international trial of highly targeted exercise in men with advanced prostate cancer, many of which are receiving the latest super anti-androgens such as Zytiga (abiraterone) and Xtandi (enzalutamide). The trial is in progress, but our initial results are that these men are tolerating the exercise program and reporting excellent improvements in quality of life and physical function. Until this and other trials in this patient population are completed, it is not known the degree of benefit of exercise in men on these drugs. Regardless, exercise confers considerable benefit to all patients in terms of both mental and physical health.

Do you have any other final thoughts about exercise for men with prostate cancer?

Dr. Newton: As a final note, it is absolutely critical that men with prostate cancer do some exercise on most if not every day of the week regardless of the stage of their disease and even when undergoing difficult treatments. The outdated recommendation of rest is now completely rejected. However, the exercise prescription must be tailored to the specific health issues of the individual patient, prioritizing those morbidities causing the greatest problems and risk of mortality.

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Join A Clinical Trial: Exercise + Advanced Prostate Cancer

S Kenfield_UCSFDr. Stacey Kenfield is an epidemiologist in the Urology Department at the University of California, SF who explores through her research how dietary and lifestyle factors impact both the risk of aggressive prostate cancer as well as the risk of prostate cancer progression. Prostatepedia spoke with her about her findings as well as a large clinical trial she’s directing with Movember that looks at the impact of exercise in men with advanced prostate cancer.

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Why did you become an epidemiologist?

Dr. Stacey Kenfield: I’ve been an epidemiologist for over 12 years. The opportunity to help men with cancer improve their quality of life and survival with the disease continues to drive me to do the work that I do. Our group strives to translate our research findings and to implement clinical trials to learn how to help men adopt the behaviors that we study, as well as to learn more about the mechanisms driving the relationships.

We’ve continued to engage men with our clinical trials, but also now educate patients who visit our urology clinics and the community who want to know what they can do once they’ve been diagnosed with cancer. We’ve continued to do our research, believing that our results on lifestyle can be used as adjuvant therapy to primary treatment of prostate cancer, and can also help formulate tailored management tools to improve prostate cancer survivorship.

What do we know about the impact of diet on prostate cancer?

Dr. Kenfield: A number of studies indicate that specific dietary factors prior to diagnosis are associated with the risk of developing aggressive prostate cancer. We also know from studies performed in men with prostate cancer that many of these same factors are associated with the progression of disease and the risk of dying from prostate cancer. Some of these factors include cooked tomatoes, due to the fact that there’s more bioavailable lycopene in cooked tomatoes versus raw tomatoes.

We also know from studies that lycopene seems to inhibit prostate cancer growth and development of aggressive prostate cancer. Another factor is fish, which is possibly beneficial due to an anti-inflammatory effect. We’ve seen that fish with especially high levels of Omega-3 fatty acids, such as salmon, sardines, mackerel, and herring, are beneficial for reducing risk of the more aggressive forms of prostate cancer.

Another factor that we believe is important is to reduce one’s intake of processed meat. Processed meat has pre-formed compounds called N-nitroso compounds. It also has nitrites, nitrates, and added salt, which seem to have cancer-promoting properties.

There has also been a lot of research on dairy and calcium in prostate cancer. In general, most studies agree that higher intakes of calcium at levels of more than 1000 milligrams per day increase one’s risk of developing prostate cancer. We want to emphasize that men with or without prostate cancer need to consume some calcium for general health, just that it should not exceed 1000 milligrams per day. For example, a cup of skim milk has about 300 milligrams of calcium and a cup of yogurt about 450 milligrams. Getting some calcium from your diet is still incredibly important for overall health.

What about getting some of these nutrients in supplement form? I know lycopene and Omega-3 fatty acids are available as supplements. What do you get from the diet that you don’t get from supplements?

Dr. Kenfield: To be honest, a lot of our studies have been focused on whole foods.

I published a study back in 2015 on supplemental selenium intake showing that high doses of supplemental selenium are associated with about a 2.6-fold increased risk of prostate cancer mortality in men after diagnosis. Both the American Cancer Society, the American Institute for Cancer Research, and others discourage people from getting their nutrients from supplements, because the data do not suggest that it’s beneficial. In all likelihood, it could cause harm if you’re taking high dose supplements; so we recommend getting your nutrients from food if you can.

Are these all factors that you would recommend for both men who don’t have prostate cancer as well as those who have already been diagnosed?

Dr. Kenfield: There are a few factors that potentially impact prostate cancer progression that have been studied recently. Plant-based fat–like nuts, plant based oils, canola, olive oil, and avocados—have been studied after a diagnosis of prostate cancer and shown to have a beneficial impact on the risk of lethal prostate cancer. Another food that we’ve focused on is cruciferous vegetables like broccoli, cauliflower, and kale. These foods have components that detoxify carcinogens that could be helpful for stopping cancer cells from growing and can also cause cancer cell death.

I’ve already mentioned tomatoes, fish, and processed meat. We also recommend that men avoid high-fat dairy like whole milk, which has been linked to a higher risk of dying from prostate cancer.

What about red meat versus chicken?

Dr. Kenfield: We focus on recommending people eat lean protein sources, so this would be skinless poultry and fish, rather than red meat, which has been associated with other chronic diseases.

What about pork?

Dr. Kenfield: We have not been recommending pork specifically. We focus on just lean protein— chicken, fish, legumes, beans, and other sources of protein, like soy.

What about organic free-range meat? Do you have any comments about the importance of hormone-free meat?

Dr. Kenfield: This has not been studied. It’s a little bit harder to study organic or free-range meat in the types of data that we collect from our patients. That question is not regularly added to our food frequency questionnaires, so it hasn’t been looked at in detail.

What impact does exercise have on prostate cancer—both on the risk of getting prostate cancer and on the risk of progression once you’ve been diagnosed?

Dr. Kenfield: A number of studies have suggested that physical activity, especially activities done vigorously—i.e. cause sweating; deeper, quicker breathing; and cause your heart rate to increase—are associated with a reduced risk of lethal prostate cancer. Early studies from our group conducted in two independent cohorts of men with prostate cancer showed that vigorous activity of 3 or more hours a week in one study and brisk walking for 30 minutes or more on most days in the other study had substantial benefits on reducing one’s risk of dying of prostate cancer, or from progression from prostate cancer, respectively.

More recent studies suggest that slightly lower levels, about four hours of walking or two hours of jogging, had some benefit. There was a fourth study that showed that you may see a benefit after just one hour of exercise per week. Overall, the data suggest that exercise is beneficial, both for the prevention of advanced prostate cancer, as well as reducing one’s risk of progression from the disease. Any aerobic exercise seems to be better than none; there is some benefit. I think for prostate cancer, one should really strive to do some of that activity at a vigorous level.

You’re talking about cardiovascular exercise. What about resistance or strength training? Has anyone looked at that?

Dr. Kenfield: There have been a number of studies, mostly focused on men on hormone therapy (ADT), that show resistance exercise offers improvements in muscle strength and certain quality of life metrics. There have been trials that focused on both aerobic and resistance exercise; those studies have reported benefits, including gains in muscle strength, improved fitness, improved balance, and less fatigue. So both resistance training and cardiovascular training are helpful.

What about lifestyle factors like not smoking and stress management. How do those factors impact prostate cancer?

Dr. Kenfield: We’ve recently developed a lifestyle score to look at the combined risk of lifestyle factors on the development of lethal prostate cancer. In addition to the dietary factors that I just mentioned (high intake of tomatoes and fish and low intake of processed meat), we also looked at high levels of vigorous activity or brisk walking, not being obese (a body mass index or BMI<30), and not smoking. This included people who had never smoked or people who had quit ten or more years prior. We created a score, which has six factors. We found that men who had 5 or 6 of these healthy lifestyle factors versus 0 or 1 of the factors had a 68 lower risk of lethal prostate cancer. That is statistically significant. This was done in the Health Professionals Follow-up Study ( In the same paper, we looked in the Physicians’ Health Study (http://phs. Many of the same variables are collected there, so we had a six-factor score and found a very similar reduction in the risk of lethal prostate cancer there. Most of the data used were collected before prostate cancer diagnosis, and up to the point of either having an outcome of lethal prostate cancer or to the end of the follow-up study. Currently, we’re looking at what lifestyle pattern after diagnosis offers the most benefit.

How are all these different lifestyle factors weighted? For example, is it more important not to smoke than to have an appropriate BMI?

Dr. Kenfield: In a separate publication on smoking, we reported that current smokers had a 61 percent increased risk of progression, which is PSA progression, as well as a 61 percent increased risk of death from prostate cancer. There is also a strong benefit for vigorous activity compared to some of the other dietary factors that have a more modest benefit. When we looked at each factor separately that are part of the score, vigorous activity had the greatest impact on prevention –we estimate that 34% of lethal prostate cancer would be prevented if men exercised vigorously regularly. I think focusing on not smoking and exercise would be critical for both prostate-specific outcomes as well as overall health and the main chronic diseases that men and women tend to die of, like heart disease.

Can you talk to us about the thinking behind the clinical trial that you’re running?

Dr. Kenfield: Some smaller clinical trials in men with prostate cancer, mostly at earlier stages of disease, have suggested that there are significant benefits to exercise on quality of life and functional outcomes. We also see from the observational research that there is an association between exercise and lower risk of clinical outcomes (I mentioned those findings above.) But we don’t know if exercise is beneficial in men with advanced prostate cancer. That was one of the critical reasons why Movember decided to fund INTERVAL (INTense Exercise foR surVivAL), a large global trial focused on advanced prostate cancer with the primary endpoint of overall mortality. We’re also interested in many secondary endpoints that need to be explored further, including exercise’s impact on progression-free survival, skeletal-related events, and other quality of life outcomes.

We really want to understand the mechanisms behind the associations, so we’re studying exercise’s effect on inflammation, insulin, glucose metabolism, androgen biosynthesis metabolism, and other pathways. We are collecting blood and urine in the study to look at mechanisms of exercise.

What can men expect to happen, step-by-step?

Dr. Kenfield: The trial is specifically examining whether a supervised exercise program versus a self-directed exercise program improves overall survival in men with metastatic castrate-resistant prostate cancer. If men are eligible, they will complete exercise tests at baseline. They’ll have their blood drawn, provide a urine sample, complete surveys, and then they’ll be randomized to either a one-year supervised aerobic and resistance exercise program that basically tapers over that year to another year of fully self-managed exercise, meaning exercise that you do on your own.

The other group is randomized to self-directed exercise. They will receive guidelines on how to do exercises on their own. During the two-year study, patients will complete exercise testing at various time points. We’ll ask them to complete surveys related to their lifestyle habits and quality of life. Each month, both groups will receive psychosocial support in the form of newsletters focused on different topics relevant to men with prostate cancer.

When you were describing the self-directed program and guidelines, my very first thought was that I’ll bet half those people aren’t even going to complete the exercises. The risk of a self-directed program is that you won’t do it if you don’t have any accountability built into the program.

Dr. Kenfield: Currently, we don’t know if supervised exercise will affect the outcome or not, and there is no evidence of superiority of one exercise strategy over another. Both groups are really important to the success of the trial. The information each participant provides will help investigators determine what levels of activities may be beneficial for men with advanced prostate cancer.

What kind of patients are you looking for?

Dr. Kenfield: We’re looking for men with metastatic prostate cancer whose disease has worsened on standard hormonal therapy. This is termed metastatic castrate-resistant disease. Patients are eligible if they’re receiving treatments in this disease phase, like Taxotere (docetaxel), Zytiga (abiraterone), Xtandi (enzalutamide), or they can be treatment naïve, meaning they’re not on these drugs yet. If a man has metastatic prostate cancer, the study coordinators will check the other study clinical criteria.

Men must be able to travel to one of the study-designated exercise facilities at least twice a week for nine months. That’s a requirement for someone who is randomized to the intervention arm. This tapers over time, but that’s a critical component of the study because we are trying to have men do supervised exercise with one of the exercise physiologists associated with the study.

Where are the study locations?

Dr. Kenfield: We have study locations in the USA, Canada, Australia, Europe, and we’re opening in China. Right now, we’re open at 12 sites; 10 other sites are in startup phase and 10 others are in feasibility stage. The study is continuing to grow, and we plan to have it continue at least through 2024.

That is a massive study.

Dr. Kenfield: I’m directing the study coordination center, based at UCSF. We have collaborators at Edith Cowan University; Dr. Nicholas Hart directs the exercise coordination center and manages the exercise testing and training for participants from Perth, Australia. At the study coordination center, we’re in charge of new site activations, patient recruitment, clinical data collection, the study databases, and data monitoring for every site, as well as the behavioral support and psycho-social support programs that are part of the study.

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Do you have any thoughts for men with prostate cancer either about the INTERVAL study that you’re running or about diet, exercise, and lifestyle choices in general?

Dr. Kenfield: Please consider joining the INTERVAL study and contacting us if you are interested and think you may be eligible. We sincerely hope that men, regardless of arm assignment, will experience some benefit from participation. And finally, to summarize, a healthy diet, not smoking, and regular exercise are critical components to reduce your risk of developing lethal prostate cancer, and may possibly prevent or delay prostate cancer progression.

We’ve seen that adopting more of these behaviors could lead to greater benefits. As I mentioned before, many of these lifestyle factors are critical for reducing the risk of other chronic diseases like diabetes, obesity, hypertension, and heart disease. Death from cardiovascular disease is still the leading cause of death worldwide in men with prostate cancer, so it’s really important to consider making these changes, not just for your prostate cancer, but also for your overall health. It will impact a lot of other aspects of your life.

Does hormonal therapy exacerbate the cardiovascular disease that many men already have?

Dr. Kenfield: Yes, hormone therapy has been linked to increased risk of insulin resistance, an increase in body fat, and decreased muscle mass. Some of these metabolic changes could lead to increased risk in developing other health problems, like diabetes and heart disease. It’s really critical that men who are on ADT or hormone therapy are exercising to counteract some of these negative effects of the drugs.

Would you say that every man with prostate cancer should be exercising?

Dr. Kenfield: Yes, I would. Our studies have focused on men with prostate cancer adjusting for the treatments that they’re on.

Would you go as far as saying that every man—even if he does not have prostate cancer–and woman should be exercising?

Dr. Kenfield: Yes.

Cardiovascular disease is the leading cause of death in women, too, is it not?

Dr. Kenfield: Yes, it is. It’s helpful to have support. Have somebody in your life that encourages you to adopt these healthy behaviors, even if it’s just a colleague or a friend. I’d encourage everyone to find someone who can help motivate them to live healthier.

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Obesity, Exercise + Prostate Cancer

Dr. Stephen Freedland is a urologist at Cedars-Sinai in Los Angeles, California and the Director of the Center for Integrated Research in Cancer and Lifestyle, Co-director of the Cancer Genetics and Prevention Program and Associate Director for Faculty Development at the Samuel Oschin Comprehensive Cancer Institute.

Dr. Freedland believes in treating the whole patient, and not just a man’s prostate cancer.

Prostatepedia spoke with him about the link between BMI, exercise, and prostate cancer.

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Have you had any patients whose cases have changed how you view your role as a doctor or how you view the art of medicine?

Dr. Stephen Freedland: I think you go into medicine because you want to – at least for me – cure disease. That implies that there’s some state of perfect health. People come in to see me and they are not in a perfect state of health. You want to restore them to this perfect state of health. I now understand that there is no such thing as a perfect state of health. We perceive a perfect state of health to mean you have no diseases. However, you’re still at risk for certain diseases. Perfect implies you can’t do any better. I don’t think that’s the case. I think we can always do something better.

I changed from a physician whose goal was to cure disease to a life coach in many ways. I help move people from less healthy states to healthier states, but it’s not a black or white thing. I don’t cure disease and then go on to the next patient. I continue to work with them, hold their hand, be a counselor, a life coach, a shoulder to cry on, someone to slap a high five when they do have a success.

I had all those experiences yesterday in my clinic. A patient gave me a hug. He called me his angel, slapping high fives with another patient, and then one patient was practically in tears because he did not have such a good prognosis. To be able to ride the rollercoaster of life with patients is a phenomenal honor. It’s a lot of responsibility, but there is nowhere else in the world that I’d rather be.

That’s an interesting perspective. It’s more like seeing people when they’re healthy to help address diseases and issues as they come up rather than having people only come to you when they’re sick…

Dr. Freedland: An ounce of prevention is worth a pound of cure.

That’s a nice segue into my first question: what do we know now about the role of BMI, exercise, and prostate cancer risk?

Dr. Freedland: BMI has been much better studied. It is very clearly delineated that elevated BMI increases the risk of aggressive prostate cancer and increases the risk of dying of prostate cancer. That’s pretty incontrovertible at this point. You’ll see a study here and there that says the opposite, but the totality of the data is pretty convincing in that regard.

Exercise is a little harder to study because you can’t simply measure it the way you can measure someone’s height and weight and know what their BMI is. You need to ask them how much they exercise. Is it vigorous exercise? Is it nonvigorous? Are you doing an hour at a time? You can get 1,000 or 10,000 steps during the day, or you can go run on the treadmill and get 10,000 steps in a half hour. It’s very different.

Collectively, I would say the data seem to suggest exercise and particularly vigorous exercise may be beneficial to prostate cancer risk, but again, that is not nearly as codified nor as consistent and clear as the link we see between BMI and bad prostate cancer.

What impact does BMI or exercise have on risk of prostate cancer progression?

Dr. Freedland: Elevated BMI increases the risk of progression, recurrence, spread to metastatic disease, and death of prostate cancer whereas exercise, again, particularly vigorous exercise, seems to be preventive for progression. But, again, this is not as well studied and is based on a handful of exercise studies. The role of BMI is pretty well established.

A lot of men on androgen deprivation therapy (ADT) struggle with weight gain and muscle loss. What are the implications of this relationship between BMI and aggressive prostate cancer or exercise and aggressive prostate cancer for those men?

Dr. Freedland: As you said, ADT induces weight gain. You get muscle loss. There’s one study from our group that showed obesity at the time of ADT increases the risk of progression to castrate resistant disease. Surprisingly, it’s not been well studied. Let’s say you decide to go on a diet and not gain that ADT weight. We’ve actually shown a low-carbohydrate diet induces 25 pounds of weight loss despite being on ADT, so the weight gain is preventable. We do know that.

What we don’t know is impact of that weight gain on progression. Is gaining all that fat mass and losing muscle bad for your cancer? Intuitively, it should be. I mean, that just stands to reason from almost everything we know about prostate cancer and metabolism, but we haven’t proven it. We have not proven that if you can prevent those things, you can prevent or delay prostate cancer progression.

It certainly has an impact on cardiovascular disease, doesn’t it?

Dr. Freedland: Presumably but, again, it has not been studied in men on ADT. We do know exercise can preserve muscle function and quality of life. We know its impact on cardiovascular markers, but actually showing that exercise prevents cardiovascular disease in men on ADT has not been shown.

What we do know is that ADT will increase the risk of diabetes by about 40%. There’s data to suggest it may increase cardiovascular disease, but it’s controversial in that, if you look at really well done Phase III trials where men either got hormones or didn’t, you see no difference in cardiovascular deaths. Those are men on Phase III trials, selected to be healthy, and followed closely by their doctors. I think what we can say is, in highly selected patients, hormones are probably safe if you follow the patient closely, but in unselected patients, they probably do have cardiovascular effects.

That’s interesting what you just said: followed closely. Are you saying that people who are on clinical trials are just by nature of being in a clinical trial followed more closely than people who are not?

Dr. Freedland: Absolutely, I mean, there’s actually data to suggest that patients on clinical trials who are randomized to the control arm, i.e. standard of care, do better than patients not on the clinical trial who got the exact same treatment. Being on a trial, even if you don’t get that fancy experimental drug, still has benefits.

What does all this mean for patients? Should BMI be a priority for all men, including men who have prostate cancer?

Dr. Freedland: Correct. BMI is the strongest lifestyle link with prostate cancer. I see patients all the time ask me what should they eat. Should they take this supplement? Should they do that? Should they take this herb?

I say: just lose weight. That’s the one thing that we know. To me, it makes the most sense to focus on getting people to lose weight. How to lose weight is a challenge. Everybody has a difference of opinion. Part of it is picking a lifestyle and sticking with it. The word diet literally means way of life. The word is Greek in origin. We need to pick a way of life that’s sustainable, that’s going to work for you, and is going to help you to lose weight. The one common thread I see among all of the diets to a certain degree is reducing simple sugars—cookies, cakes, candies. There is not a diet that I’m aware of out there that says, “Nah, don’t worry about it. Eat all the cookies you want.”

You mean there is no chocolate cake diet?

Dr. Freedland: Correct. The low-fat, the whole-food plant-based folks will say eat all the vegetables you want. The low carb people will say eat all the meat you want. But all of them agree, even though they’re almost diametrically opposite, that cookies aren’t good.

What would you say about exercise? Would you tell men to prioritize BMI over exercise?

Dr. Freedland: To me, they go together. Do you know what the number one cause of death in men is?

Cardiovascular disease.

Dr. Freedland: Cardiovascular disease. What’s the number one cause of death in men with prostate cancer?

Cardiovascular disease.

Dr. Freedland: Cardiovascular disease. To me, if I can use a man’s cancer to scare him into eating right, losing weight, and exercising, I’ve probably done him a lot of good. Whether I’ve helped the cancer or not, in my mind, isn’t as important. Even if the exercise won’t help his prostate cancer, I’ve definitely done good from a cardiovascular point of view. To me, eating right and exercising go hand in hand. I don’t think you can focus on one over the other. Are you going to wear your pants today or are you going to wear a shirt? You need both, right? You’d look silly going around the workday without either one of those.

I guess it’s hard to lose weight without exercising.

Dr. Freedland: Amazingly, it’s not that hard to lose weight without exercising. Exercise is not a great way to lose weight. It’s a great way to get fit. It’s a great way to get healthy. Not a great way to lose weight. Not that it makes weight loss worse, but it actually doesn’t help weight loss much. Weight loss ultimately is about eating less.

Right, eating less than you spend, right?

Dr. Freedland: Correct, taking in less than you burn, and that’s where the whole-food plant-based diet comes in. You’re eating a lot of filling food that’s not calorie dense. It fills up your stomach and you feel full, even though you haven’t taken in a lot of calories.

You can also go to low-carb, which is very calorically dense. Fat and protein fill you up more than carbs, so you end up losing weight. There’s a lot of different ways to go about losing weight. There are general low fat diets. There’s Weight Watchers. There’s a lot of ways to lose weight. But exercise is something you do for your health, not to lose weight. The problem is that a lot of people start exercising to lose weight and then get frustrated and give up. You don’t exercise to lose weight. You exercise to get healthy. You eat less to lose weight.

Do you think discussions about BMI and exercise should be a part of every prostate cancer patient’s initial meeting with a doctor, whether he has low-risk or aggressive cancer?

Dr. Freedland: I think it should be a discussion with every patient at every visit regardless of the diagnosis. It should be part of a wellness visit, a hypertension visit, a high cholesterol or a BPH visit, or a prostate cancer visit. I think it needs to be integral. We need to not think of ourselves as prostate cancer doctors, or bladder cancer doctors, or whatever the case may be. We need to think of ourselves as doctors.

Most patients have more than one disease anyway. If you treat just the prostate cancer, then you’re ignoring the cardiovascular disease.

Dr. Freedland: Correct. It doesn’t mean we need to manage the cardiovascular disease and manage the blood pressure, but we need to be aware of it. We all went to medical school. But there’s more to a patient than his PSA and Gleason score.

Any final advice for men about obesity and prostate cancer?

Dr. Freedland: I always keep in mind the age-old adage: genes load the gun, but lifestyle pulls the trigger.

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Diet, Exercise + Prostate Cancer


This month, Prostatepedia talks about things you can do to help yourself—diet and exercise.

Dr. Snuffy Myers frames this month’s conversations for us:

There is a clear consensus that it is a good idea to get thin and exercise. First, it is good for your general health as it reduces the risk of hypertension and diabetes as well as the cardiovascular complications associated with both of these diseases. Exercise has also been shown to preserve cognitive function and is beneficial for common neurologic diseases like Alzheimer’s and Parkinson’s.

Second, exercise helps minimize the side effects of most of the treatments used for prostate cancer. Finally, as several interviewees discuss, exercise is associated with a lower risk of death from prostate cancer.

In my experience, it is not difficult to convince prostate cancer patients that they should exercise. However, it is very difficult for patients to initiate and maintain an exercise program that is comprehensive and vigorous on their own. It turns out that it is very important to join an exercise facility and get professional guidance. Ideally, you would have a personal trainer tailor your program to your abilities and needs. However, this can be expensive. A sound alternative is to attend group exercise sessions. Water aerobics classes are very gentle on knee and hip joints and practical for even very obese patients. Spin or indoor cycling sessions can offer a very intense cardiovascular workout with less risk of knee or hip trauma than running. Resistance exercise is important and, done properly, weight lifting has a relatively low risk of injury. However, most patients do not know how to squat or deadlift properly, so professional supervision is again important.

In his conversation, Dr. Stephen Freedland states that successful weight loss requires a diet that the patient can stick with long term. I would add that a diet is more likely to be successful if you believe in it yourself. In other words, there is a strong placebo effect.

This is not to say that anything goes. A diet based on cured meats, cookies, and cinnamon buns would not be healthy and would not promote weight loss. Some low carb diets do end up including cured meats like bacon.

In my clinic, we ended up recommending a Mediterranean diet as most patients found that easy to maintain over a period of years. The major pitfall was that some patients overate foods like pasta, leading to overly high carbohydrate intake. As a result, we emphasized moderate carbohydrate intake.

Charles E. Myers, Jr., MD


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Living A Normal Life After Prostate Cancer

Dr. Stephen Freedland is a urologist at Cedars-Sinai in Los Angeles, California and the Director of the Center for Integrated Research in Cancer and Lifestyle, Co-director of the Cancer Genetics and Prevention Program and Associate Director for Faculty Development at the Samuel Oschin Comprehensive Cancer Institute.

Dr. Freedland treats the whole patient and not just a man’s prostate cancer.

He frames this month’s conversations about stress, depression, and prostate cancer.

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Historically, the goal was to cure cancer. We don’t really cure other major medical problems like heart disease, diabetes, high blood pressure, or high cholesterol: we manage them. Cancer, in general, and prostate cancer, in particular, are becoming chronic diseases. Occasionally, we need to do something more aggressive, but we really just need a management strategy so that people can live normal, healthy lives even after being diagnosed with cancer.

With this shift from quantity of life to quality of life comes an opportunity for us to have conversations about how prostate cancer and its treatments affect daily life. People are now younger at diagnosis than ever before. They’re still active. They’re still working. They’re still productive members of their families and of society.

How do we help them maintain that while providing the best cancer care? The challenge is how to marry those two. It’s not enough to focus on Gleason score, PSA, and stage. The focus is on the patient. On the person. It’s not just about the numbers.

I applaud Prostatepedia for delving into this subject matter with some very engaging conversations with some of the world leaders on the topic. I work very closely with Dr. Arash Asher at Cedars-Sinai Medical Center. We focus now on nutrition, exercise, and psychosocial health. It’s really spectacular to see. Men are able to maintain much of their quality of life and sometimes feel better than ever.

At the same time, we’re realizing that what works for one patient will not necessarily work for another. There is no shortcut to sitting down with a patient, understanding his needs, goals, and desires, and then working together to come up with a care plan that manages his cancer and his side effects. We want to keep you psychologically strong and able to fight your cancer–but also to live your lives.

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Vitamin D, Omega-3 Fatty Acids, Curcumin + Prostate Cancer

Dr. David Levy is a Clinical Associate Professor in the Department of Urology at the Cleveland Clinic.

Dr. Levy spoke to Prostatepedia about his clinical trial looking at the impact of vitamin D, curcumin, and Omega-3 fatty acids on prostate cancer.

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Can you explain the thinking behind your clinical trial on vitamin D, Omega-3 fatty acids and curcumin in prostate cancer?

Dr. David Levy: Well first let me say there are a number of people involved in this program without whom it would not be where it is today.

I was extremely fortunate. When I finished my residency in Cleveland, I went to MD Anderson Cancer Center in Houston, Texas to do a cancer fellowship.

At that time, we didn’t really understand why cancer occurs and how to treat it. The attitude was: “Cut it out. Radiate it. Give chemo.”

We’re now twenty years down the road and while medical knowledge has advanced tremendously, what are we still doing? Cut it out. Give radiation. Give chemo. People with cancer keep coming and coming. It’s like a conveyor belt. They don’t stop.

About five years ago, I bought an abandoned farm here in Northeast Ohio. The goal was to make it an organic certified produce farm, which I did over three years. In learning about the process to make our farm certified organic, I had to review all the pesticides and chemicals that had been put into the soil and what we had to avoid for over three years to gain the certification. With all these pesticides and chemicals come known side effects.

There is a journal called the Journal of Organic Sciences, which ran a 25-page article on the use of a very common weed killer. Going back to the 1970s, there is a direct correlation of the increased use of this weed killer in commercial agriculture with an increase in liver cancer, colon cancer, kidney cancer, kidney failure, lymphoma, leukemia, thyroid, and prostate cancers. Every cancer went up. They all paralleled the increased use of this common weed killer.

When I read that article, I started to think that there has to be some correlation between environmental exposure and cancers. I started to ask: If you change the environment in which the cells live, do you change their behavior? That has been studied a few times and the results published. Studies have shown the influence of vitamin D on prostate cancer behavior, the impact of Omega-3 and Omega-6 fatty acid ratios on prostate cancer behavior, and the impact of turmeric curcumin on biochemical pathways in the cells. I was thinking about all of that as I came to design the trial.

If you look at populations across the world, prostate cancer rates vary quite dramatically. India, China, and Japan have some of the lowest rates of anywhere in the world. The rate in India is 25 times less than that in the United States, England, France, Germany, Norway, Sweden, or Finland. Why is it that? Men in India all have testicles and testosterone and prostates, but they don’t have prostate cancer. The same goes for Japan and China.

There are pretty interesting differences in terms of the eating habits of these populations and the disease processes that are common in the societies.

It turns out, as far as we can tell, that meat and dairy feed prostate cancer. What do we see in this country on NFL Sunday? What do they serve? They serve hot dogs, French fries, chicken fingers, chicken nuggets, chicken wings, and hamburgers. All of these foods are very high in Omega-6 fats. No one goes to the ballpark to get a bag of broccoli. That doesn’t happen. No one goes there to eat apples.

When we look at our society in terms of the food choices, the foods that are heavily advertised are fast foods, pizzas, and sodas. High sugar loads, high glycemic index foods, and animal fats are all very well correlated with prostate, breast, pancreatic, and colon cancers.

I looked a little further into vitamin D and asked, “Is there a correlation with vitamin D and prostate cell behavior?”

It seems there is. One published study looked at 71,900 men—which is a pretty substantial population—for six and a half years. They found that the lower the vitamin D levels in the blood, the higher the patients’ PSAs, the higher the likelihood of a positive prostate biopsy, and the more aggressive their cancers.

Another vitamin D study published by the SEER committee, which is a national organization that correlates hospital reported statistics throughout the country, looked at 20,000 men. Again, they found low vitamin D, higher PSA, and higher odds of a positive prostate biopsy with significant disease.

Other studies correlate vitamin D levels with prostate cell behavior. It turns out that vitamin D binds on the prostate cell to the androgen receptor. That is where testosterone binds, and testosterone is the main food for prostate cells. Vitamin D binds to this receptor as well. As best we can tell, with low vitamin D levels, the prostate cell machinery churns along like a steel furnace. When the vitamin D levels go up, something happens to the cells’ metabolic rates

Across the country, almost all of the residents of the states north of South Carolina border and from East to West

Coasts are low in vitamin D. I haven’t tested anybody here in Cleveland in almost three years with a normal vitamin D level.

What about turmeric curcumin?

Dr. Levy: Tumeric is used in curry and it contains curcumin. Curcumin is a really good anti-inflammatory. It’s a naturally occurring COX-2 inhibitor. (Celebrex was a COX-2 inhibitor.) It turns out that curcumin has a far greater impact on the biochemistry of cells than just an anti-inflammatory. Curcumin impacts what is called the Hypoxia-inducible factor 1-alpha. This is a factor made in the cells that is involved in their ability to recruit new blood vessels to get more oxygen and more nutrients. Curcumin disrupts that cycle.

Curcumin disrupts the mesenchymalepithelial cell transformation. The mesenchymal-epithelial cell transformation is a process that allows cells to gain the ability to climb outside the prostate and spread to the lymph nodes and bones. Curcumin also impacts the diclofenac acid pathway, which is part of the cell’s Omega-6 metabolic pathway.

There are new publications that show curcumin increases cellular sensitivity to radiation treatment. There are some studies that show it increases the cell’s susceptibility to chemotherapy.

There are over 300 publications in the National Library of Medicine on curcumin and prostate cancer right now. When I started this work about 3. years ago, there were 13 publications on curcumin and prostate cancer. There were so few publications I couldn’t even include them in my suggested regimen to patients. Now, there’s no way we can ignore it.

In my opinion, to not include curcumin would be a disservice to patients because it has such a tremendous impact on cellular behavior without being toxic in any way to the kidneys, the liver, the intestinal system, or the cardiovascular system.

There are very few reported side effects of dosing curcumin. Patients have taken as much a 6 grams per day in capsule form in a study protocol to impact their prostate cancer. We give 2,000 milligrams per day, and in 27 months have not seen any side effects that would curtail our continued use of the supplement.

Are you giving men vitamin D, omega-3 fatty acids, and curcumin all at the same time and then measuring the outcome, or are you separating them out into different groups?

Dr. Levy: No. We’re giving them all together.

After you give patients a combination of the three supplements what kinds of measurements are you doing?

Dr. Levy: We measure the fatty acid ratios in the body. We measure the three individual components of the fish oil:

EPA, DHA, and DPA. We measure the Omega-3/Omega-6 ratios in the blood. We measure linoleic acid levels in the blood. We measure vitamin D levels, and then titrate their doses to get vitamin D levels up to our target range.

There is nothing you can do to measure curcumin except give the dose of the appropriate manufacturer’s preparation.

We spent a lot of time figuring out what was going to get to the cells most efficiently.

And of course, we change the diet.

But the end point of our study is genetics. We do a tissue biopsy at the time of diagnosis. Then the men go on nutrition modification and supplements for a minimum of nine months. After nine months, we repeat the prostate biopsy and do a side-by-side genetic comparison of the prostate tissue from before the diet and supplements regimen with the tissue from after the diet and supplements regimen. Then we see what kinds of changes we have caused by changing the environment in which the cells live.

What kind of patients are you looking for?

Dr. Levy: For the purposes of this genetic study, we are specifically looking at people with low-risk prostate cancer who are on active surveillance or who are candidates for active surveillance.

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Diet + Lifestyle During Treatment

Ms. Greta Macaire is a registered dietician at the University of California, San Francisco.

She spoke with Prostatepedia about the types of recommendations she makes for men with prostate cancer during treatment.

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What do you recommend for men about to start radiation, have surgery, or begin chemotherapy?

Ms. Greta Macaire: I always tell men undergoing radiation, surgery, or chemotherapy that there will be side effects from those treatments. They may need to modify their diet.

For example, patients who get radiation to the prostate bed in the pelvic area (or if lymph nodes are involved) can experience side effects such as gas, bloating, loose stools, and diarrhea. To decrease these side effects, they may have to modify their diet. These are almost always temporary recommendations, though, so it can be really confusing for men.

As a good diet for men with prostate cancer, everyone would recommend a lot of broccoli and vegetables. But men who go into radiation might get gas, bloating, and diarrhea, so they may need to avoid gas-producing vegetables and acidic foods like tomatoes to decrease these side effects. We would also recommend less fiber and more cooked vegetables in that case. But I always let them know these are temporary changes.

Once they recover from radiation, they’ll be able to introduce all these foods back into their diet gradually. It can be a little unnerving for them to think about backing off those foods that they feel are so important. The digestive tract usually heals pretty quickly from something like radiation, so it’s just temporary. Typically, we incorporate those foods back in within a couple of weeks after treatment.

Surgery can also result in gas and bloating because of the pain medications. Constipation and gas can be really uncomfortable because of the surgery. Again, that’s usually temporary.

Any dietary changes before chemotherapy?

Ms. Macaire: The most common side effect I hear about is taste changes: some foods are not appealing or taste like cardboard or metal. Nausea and decreased appetite are other common side effects.

You may have to plan out what you’re going to eat. Eat smaller meals, and eat more often. That way, you’re not getting too much so you’re not going to feel bloated and uncomfortable, but then you’re not going all day without eating, which will make nausea worse. If you experience a metallic taste, we can look at ways to tweak the flavor profile of foods to make them tastier.

Sometimes animal protein brings out the metals in food. There’s more iron and things like that even in chicken or fish. Choose alternative protein sources that don’t have as much of the metallic flavor. Lemon juice can brighten up flavor if everything tastes bland. These small modifications can help with the side effects.

I think it’s comforting for people to hear that these changes are temporary. You’re going to like food again. When you’re done with chemo, things will taste good again. Hold tight.

One of the big side effects of androgen deprivation therapy (ADT) is that men tend to gain weight quickly. What do you recommend for men on hormonal therapy?

Ms. Macaire: We strongly recommend physical activity. The research is pretty consistent on physical activity. Cardiovascular exercise is important, but resistance training is also important. Resistance training maintains lean body mass, which keeps the metabolism higher. The more muscle they can maintain and not lose due to hormone therapy, the more they can keep their body composition on track.

Men on hormone therapy need to be careful about what they eat, especially with foods that can cause weight gain: white foods—which can cause abdominal weight gain—like refined grains and sugary beverages (soda, fruit juice), desserts, and pastries. It’s really important to eat more green leafy vegetables, fill your plate with filling, high-fiber foods. Make at least half your plate non-starchy vegetables, fill a quarter of the plate with lean or plant protein and limit grains or starchy vegetables like potatoes, corn, or peas to no more than the other quarter of the plate.

I wouldn’t recommend a low-carb diet by any means, but eating lots of vegetables and including a lean protein with each meal will help to keep blood sugar levels stable, to prevent spikes and drops.

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Statins, Cholesterol + Prostate Cancer

Dr. Lorelei Mucci specializes in prostate cancer epidemiology and her research focuses on cancer risk and mortality in populations across the globe.

Prostatepedia spoke with her about cholesterol, statins and prostate cancer.

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What is the role of cholesterol in prostate cancer? And statins?

Dr. Mucci: This is a very interesting and important area of research. There have been a number of well conducted epidemiological studies showing that high cholesterol levels are associated with a higher risk of more aggressive prostate cancer.

Cholesterol synthesis and biosynthesis pathways seem to be altered in men with more aggressive forms of prostate cancer. Cholesterol can be used to synthesize androgens; they’re the backbone for androgen synthesis.

The epidemiological evidence for the association between statins and the decreased risk of advanced prostate cancer is quite good. The question is: Is this a true association? Is the mechanism specifically through cholesterol-lowering? There seems to be some evidence that the lowered risk of aggressive prostate cancer may act through regulating cholesterol levels, but some of statins’ effects on aggressive prostate cancer may be independent of cholesterol.

I do think the data are fairly strong around statins. Again, whether that is totally through cholesterol-lowering or other specific pathways is not clear. (See pdf/10.1200/JCO.2017.74.7915 to read more of Dr. Mucci’s thoughts on statins and prostate cancer.)

Do statins impact the effectiveness of drugs like Zytiga (abiraterone)?

Dr. Mucci: I am a co-author on a study looking at the effect of statins on androgen deprivation therapy. One of the pathways that statins use to get into prostate cells is the same set of pathways that androgens use.

One thought is that statins may help these other antiandrogen medications by blocking the cellular pathways androgens use. There is both interesting human and experimental data suggesting that statins may benefit these antiandrogen therapies.

This is a very interesting area of research. It might be early on in terms of evidence, but I do think it will be really important to look at how things like statins—and potentially other things like aspirin—are associated with a lower risk of aggressive prostate cancer. It may be really important to think about the possible impact on treatment that other medications that men may be taking at the same time as medications for prostate cancer could have. We may be able to repurpose drugs we hadn’t really thought about before for prostate cancer either on their own or in combination with other therapies.

Should we prescribe statins for all men with prostate cancer? I don’t know that the evidence is good enough for us to recommend that, but we do feel that statins are probably very safe for men who have prostate cancer. If a man with prostate cancer has high cholesterol levels and a high heart disease risk, I think going on a statin is safe. I think it’s premature to suggest that we put all men on statins, though.

Do we have long-term data on statin use from the cardiovascular community?

Dr. Mucci: Looking at secondary outcomes like prostate cancer?


Dr. Mucci: That’s a great question. A lot of the cardiovascular studies have been small, but if there’s enough follow-up, and if you pool all the studies together, that may be enough. I would be surprised if someone hasn’t started looking at that.

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Exercise + Metastatic Prostate Cancer?

Professor Rob Newton is the Associate Dean of Medical and Exercise Sciences and the Co-Director of the Exercise Medicine Research Institute, School of Medical and Health Sciences at Edith Cowan University in Perth, Australia.

Prostatepedia spoke to Dr. Newton about his exercise for men with metastatic prostate cancer.

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What exercises do you recommend for men with metastatic prostate cancer?

Dr. Rob Newton: Traditionally, the recommendation for patients with metastatic disease was to rest. The patient should avoid physical activity, and weight/resistance training in particular, due to concerns that bones might fracture at a point of weakness.

We’ve run two studies that challenge this idea. One has been published; the other is ongoing. We’ve been exercising men with metastatic prostate cancer and women with metastatic breast cancer and we’ve seen no adverse events—no increase in pain medication. We’ve seen good physiological responses and improved fitness, strength, and muscle size. It appears that in a well-controlled environment, with appropriately qualified personnel, the risk of a fracture at the site of metastasis is very low.

We use accredited exercise physiologists, but in the United States, men should find a clinical exercise physiologist in a good, monitored facility. Patients respond very well.

It’s counterproductive to recommend to patients with metastatic disease that they rest because they’ll only decline faster and die quicker. Physical inactivity is not an option; they have to exercise. The challenge is to implement this safely and effectively.

Clearly, a home-based program is inadvisable. These patients most likely will have cardiovascular issues, so they’re at risk of having a heart attack or stroke. Their program needs to be monitored by the right personnel using the correct equipment with sound emergency procedures. Our recommendation—and what we have implemented—is a clinic-based program, supervised by exercise physiologists.

In those particular clinical trials, we designed a program so that the exercises avoided the side of the metastasis. For example, if they had a lesion in their left femur, then we wouldn’t exercise that limb to avoid overloading it and causing a fracture.

Some preclinical work in an animal model showed that controlled exercising on the metastatic site compressed tumor progression. When you load bone, bone cells send chemical and electrical signals to other cells that they should respond, generally by laying down more bone to make the bone stronger. Those same electrical and chemical signals also suppress tumor cells.

We have two trials running currently —one in breast cancer and one in prostate cancer—looking at exercise for patients with metastatic spinal lesions. We’re doing controlled isometric contractions to produce compressive load on the side of the lesion. Then we’re using sophisticated MRI techniques to monitor the volume of the metastatic tumors.

Those two studies are ongoing but, again, we’ve had no adverse effects. We have no exacerbation of bone pain. We’re just waiting now for the complete studies to see if, relative to usual care, we’ve observed a slower rate of growth of the bony metastases.

What would you suggest to a man with metastatic disease reading this? Contact his doctor to develop an exercise program?

Dr. Newton: If he has metastatic disease within the skeleton, then he has to avoid any risk of falling. Obviously, contact sports are out, as well as waterskiing, skiing, and snowboarding. It’s critical he exercises. It’s critical he does both aerobic and resistance exercise.

Currently, we recommend he avoid loading the specific site of the metastases, but in the near future, we may see a prescribed exercise program that targets and controls loading. An oncologist or physician would not be able to prescribe an exercise program because they have no background or training in exercise physiology. You have to have the right medical professional give the right exercise prescription.

In Australia, we’re strongly encouraging people to seek the consultation of an accredited exercise physiologist. In the United States, you would look for a clinical exercise physiologist. The American College of Sports Medicine ( now has specific certifications for exercise oncology, but as this is a relatively new field, there are not many of these health professionals out there at the moment. But the field is growing and specialists can be found.

What if a prostate cancer patient can’t find the right exercise doctor?

Dr. Newton: Visit Movember, which has some support programs in the United States. In Australia, which is as big a country geographically as the United States, we now manage around 2,000 men with prostate cancer entirely via telephone and online.

You mentioned the American Cancer Society’s recommendations for exercise as 75 to 150 minutes a week. Do you think that’s adequate?

Dr. Newton: Absolutely. Seventy-five to 150 minutes per week of moderate to vigorous aerobic exercise and two or more resistance training sessions per week is sufficient to maintain normal health. That means that if you do vigorous exercise, 75 minutes is sufficient. That is for healthy people. If you’ve got cancer, you’re going to have to be more specific about the exercise you do. You’re going to have to do exercise medicine that will give you the best cancer survival.

It’s highly problematic to recommend to patients that they be more physically active. For example, if a patient likes walking and decides to do more walking, that might benefit some aspects of their health. But walking will not benefit a man on ADT who has rapidly developing osteoporosis and sarcopenia (muscle loss). Walking will benefit his cardiorespiratory system, but that probably won’t be what kills him.

Most likely, he’ll become dysfunctional due to low muscle mass and he’ll have an osteoporotic fracture. If it’s in the hip, he probably won’t survive it.

These generic recommendations are helpful generically, but if you have cancer you really need to be assessed by a specialist. That specialist can determine your life-limiting factor and then prescribe medicine tailored to reduce that factor.

Precision exercise medicine?

Dr. Newton: Exactly. We’re working a lot with men with advanced disease, and the American Cancer Society guidelines are difficult for them, particularly if they’ve got cachexia, or muscle wastage. Most likely, 150 minutes per week of moderate intensity exercise is counterproductive. That makes for a greater energy imbalance; they will lose more muscle.

You’ve got to be a little bit careful, particularly with patients who are having a difficult time due to treatment or the stage of their disease. Exercise must be targeted.

That said, any exercise is better than none. The overwhelming clinical evidence and research show that men with prostate cancer—or anyone with any cancer—regardless of the stage of disease, even while undergoing difficult treatments, must be physically active on most, if not, every day of the week. If they adopt a rest strategy, then they will only deteriorate faster. We totally reject the rest strategy; it doesn’t work.

Any amount of physical activity is beneficial and will likely increase survival, but a targeted exercise prescription will be far more effective and safer. We must move to the next stage where highly tailored exercise medicine is standard.

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