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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 (https://sites.sph.harvard.edu/hpfs/). In the same paper, we looked in the Physicians’ Health Study (http://phs. bwh.harvard.edu/phs1.htm). 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.

Join us to read the rest of this month’s conversations about diet, lifestyle, and prostate cancer.


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Patients Speak: Anxiety, Depression + Prostate Cancer

Roger G. is an Australian man with prostate cancer.

He spoke with Prostatepedia about how he dealt with anxiety and depression during his prostate cancer journey.

How did you find out that you had prostate cancer?

Roger: My general practitioner had been checking my PSA since 1999. I’d had some issues with urination. He wasn’t too concerned because my PSA hadn’t changed much. In 2003 it had risen to 3.8. In 2004, he said I should get another PSA test but said to leave it until early December, which I did. By that time it was up to 5.6. He referred me to a urologist who said, “We’ll do a biopsy. No hurry. Come back after Christmas.”

I went back to see him in January. The cancer looked pretty well contained. My Gleason score was 3+4=7. He said we’d have to operate, but there was no rush. At that stage, I was a little bit anxious about it all. I thought: Here we go. Just my luck to have cancer, but let’s get on with it. The urologist said, “If it has spread, which I don’t think it has, you can go on hormone treatments. Lots of people get 12 more years with that. Don’t worry.”

I had the bone scan to check if it had spread. Nothing was found in my bones. I had them book me for surgery as soon as they could. The surgery went well. Three months later, I went back to see him. My PSA was 4. He said, “Surgery failed.”

A week later I had another PSA test. It was 5. I started to feel a little bit anxious, but he told me not to worry. He sent me off for a PET scan, which took a little bit of organizing. This was back in 2005 when the PET scan machines were new. They didn’t even know which PET scan to give me. I now know that the PET scans I had were part of a study to determine which was best for prostate cancer. I had one scan and then another. It lit me up like a Christmas tree. There were three big red dots well apart and away from where my prostate was. I was pretty anxious about it all.

How did you deal with that feeling of anxiety?

Roger: I asked, “How long have I got?” They estimated two to five years. I asked about surgery? “No,” they said, “That’s like weeding a garden.” What about radiation? They said they’d have to burn my guts out. I asked what to do. They just told me to “Keep fit and come back in three months.” I was 59. My experience with cancer in my family was pretty grim. My dad was diagnosed with cancer and died three weeks later. It wasn’t prostate cancer, though. My aunt died from lung cancer.

One of my sisters said it was breast cancer, but I didn’t know that at the time. She died pretty soon after her diagnosis. My dad’s brother was 72 when he told us he had lung cancer on Boxing Day in 1995. He was dead by Easter. I was a mess. I would see healthy people and say to myself, “How come you are okay and I have only a few years?” The black dog was giving me a hard time.

But that’s when I organized myself to see the psychologist at the hospital. I had a breakdown. I saw her every week and just talked about how things were going.

She suggested I obtain the Guided Mindfulness Meditation CDs by Jon Kabat-Zinn and start with body scan meditations. I bought the discs. These helped a quite a lot, and I felt as though I was doing something to cure the cancer.

Then, by chance, I went to a support group meeting in one of the Melbourne suburbs—pure chance. I couldn’t find anybody at the meeting who was in the same boat as me. Everybody I met had either had surgery and was all clear, or they were just waiting and watching. But also at that meeting was a motivational speaker. He was fantastic. He talked about how it was mind over matter and about self-talk. He mentioned Lance Armstrong’s book: It’s Not About The Bike.

It’s about turning things around with this self-talk stuff. It all gets to you. I’ve only got a few years to live. I want to really enjoy the rest of my life. Now, I say to myself, “You’re going to be okay.”

Anxiety had me looking at the dark side. Everything on the TV was death. It wouldn’t matter what it was. It was all death to me. It was all why me? A good friend invited me around to his place for a drink and we enjoyed a bottle of red wine. For the first time in two months my nerves settled, and I knew that I could put the black dog in his kennel. Things took a dramatic turn. My boss, who was very understanding, told me of his brush with cancer and how he was given the all clear.

A work colleague told me about his 80-year-old father who had been told he only had a year to live when he was 40. When I took my first PSA test in 3 months, my general practitioner said it might be down. And it was: 3.4!

Cancer is tough. I’m sure most people wonder why me at some point.

Roger: I went through a period when I had a tough time. I was on a hormone-suppressing drug when my PSA went back up to about 20. I got a little bit depressed once

I started on that. I went back to the meditation tapes. There were other issues, too, with loss of libido and putting on a bit of weight. I use the meditation CDs and selftalk. I keep myself fit. I do a good bit of resistance training and stretching.

In June 2016 I had another serious mental breakdown. My general practitioner put me on a mood enhancing drug. Now I’m feeling terrific and energized.

And you lead a support group, don’t you?

Roger: I’m the secretary there. That keeps me busy. I play golf three days a week. I walk around the golf course, dragging my clubs around behind me. Even though I was depressed, I still played golf and worked out at the gym.

Do you have any advice for other men facing similar circumstances?

Roger: Prostate cancer is a chronic disease. If you get a black mood, use self-talk. Talk to yourself inside your ear: “You won’t have any symptoms. They don’t happen. If you do get a bit of pain, well, you can just let them do a bit of radiation.”

You’ve got to keep in touch with your oncologist, just to see if you are eligible for one of the new effective treatments. Work out because your bones degrade when you’re on hormone treatments. Exercise is medicine. Get your heart beating and get your muscles working. This will give you a sense of control over your destiny.

If you are anxious or depressed, see your general practitioner. The medication my general practitioner prescribed sorted that out (and decreased the intensity of the hot flushes).

I enjoy my grandkids. Two of my daughters are married. I’ve got four grandkids. It makes me see the joy. I am really looking forward to all the joys of old age. I had a friend who is about 12 years older than me and he has dementia. I think prostate cancer is a better route.

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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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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 (http://www.acsm.org/) 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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