Posted: Mar 30, 2017
Dr. Snuffy Myers talks further about CT scans and cancer risk.
Posted: Dec 10, 2018
Dr. 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Dr. Kenfield: Yes, I would. Our studies have focused on men with prostate cancer adjusting for the treatments that they’re on.
Dr. Kenfield: Yes.
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.
Dr. Snuffy Myers talks further about CT scans and cancer risk.
Posted: Dec 07, 2018
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.
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.
Dr. Freedland: An ounce of prevention is worth a pound of cure.
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.
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.
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.
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.
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.
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.”
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.
Dr. Freedland: To me, they go together. Do you know what the number one cause of death in men is?
Dr. Freedland: Cardiovascular disease. What’s the number one cause of death in men with prostate cancer?
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.
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.
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.
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.
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.
Dr. Freedland: I always keep in mind the age-old adage: genes load the gun, but lifestyle pulls the trigger.