THE IMPORTANCE OF PHYSICAL ACTIVITY FOR MEN WITH PROSTATE CANCER

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THE IMPORTANCE OF PHYSICAL ACTIVITY FOR MEN WITH PROSTATE CANCER

ONC_2019_0012_NC 09.2019

EXERCISE PROGRAMME FOR MEN WITH PROSTATE CANCER UNDERGOING ANDROGEN DEPRIVATION THERAPY


CONTENTS WE WERE MADE TO MOVE

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PHYSICAL ACTIVITY – HOW MUCH IS ENOUGH?

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POSITIVE EFFECTS OF PHYSICAL ACTIVITY

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HOW DO WE GET MORE PEOPLE TO TAKE EXERCISE?

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PROSTATE CANCER, TREATMENT AND PHYSICAL ACTIVITY 10 PATIENTS WITH PROSTATE CANCER HAVE A LOT TO GAIN FROM EXERCISE

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WHAT SHOULD YOU REMEMBER?

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PRACTICAL ADVICE

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REFERENCES

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WE WERE MADE TO MOVE We were born to run, or at least to move. Our genes have barely changed from when we lived in caves and had to hunt for our dinner – until now, when we can order a meal online to be delivered to our door. The fact that we move less than in previous eras affects us in a number of ways, not least when it comes to diseases and ill health. Our lifestyle, particularly in the West, has changed radically over the past 60–70 years. We move less and we spend more time sitting down.1 This has led to an increase in so-called lifestyle diseases, e.g. diabetes, cardiovascular disease and obesity. Those countries that have actively worked to reduce smoking and blood lipids, and to improve dietary and exercise habits, have considerably fewer problems with these diseases.

It is difficult to know precisely how much less exercise we are getting than in previous eras, as there are no reliable studies. However, studies have been conducted involving the Amish population in the USA, for example, whose lifestyle today is similar to what it was hundreds of years ago. One study, in which members of the Amish population were equipped with pedometers, showed that they took 15–18,000 steps per day. That is approximately 10,000 steps more than the average person takes in a day.2 Physical inactivity is often described as an epidemic, because it is spreading to an increasing number of countries as they become industrialised. Today WHO ranks physical inactivity as the fourth biggest cause of ill health in the world.3 Much needs to be done to halt this trend, as current research predicts that the problem will become even worse in the future.

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PHYSICAL ACTIVITY – HOW MUCH IS ENOUGH?

In the Nordic countries there are recommendations for how much people ought to exercise to achieve good health.4

A survey has been carried out in the Swedish population, in which two-thirds of respondents said that they meet the recommendations for physical activity.5

150 minutes of physical activity spread over 5 days, i.e. 30 minutes at a time, is the current recommendation. The exercise should be of medium intensity. In addition, people should perform low-intensity physical activity, so-called everyday activity.

Less positive results are seen in other studies when more advanced measuring methods have been used, e.g. accelerometry. These studies reveal that just one-­ third of middle-aged people get enough exercise.6 Among young people it is probably even fewer.

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Fitness is partly hereditary, but it can be improved enormously through exercise. Fitness is also the most important factor for predicting future health. Ordinary everyday activity is also highly significant.

There has been great focus on the increase in sedentary behaviour in recent years. People who are already unfit or physically inactive are those who are most negatively affected by a sedentary lifestyle. So far there are no recommendations for how much people should avoid being sedentary other than: as little as possible. Perhaps research will be able to provide a more exact answer in the future. The recommendations will probably be based on an individual’s physical functionality and how much they exercise.7 In addition to physical inactivity, overnutrition naturally contributes to obesity and poor health. Unfor-

tunately, the increase in lifestyle-related ill health seems to affect weaker socioeconomic groups most. Here a number of unhealthy lifestyle habits are evident, such as physical inactivity, sedentary behaviour8, more unhealthy eating habits, obesity, more smoking and higher alcohol consumption. This contributes to an inequality in the disease panorama. To summarise, people today are more overweight, have more diseases as a result (diabetes, high blood pressure, high blood lipids), are less fit, are weaker and are probably less able to cope with stress than their forefathers. It is, however, possible to change this trend!

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POSITIVE EFFECTS OF PHYSICAL ACTIVITY IF EVERYONE FOLLOWED THE RECOMMENDATIONS FOR PHYSICAL ACTIVITY, THE FOLLOWING WOULD HAPPEN: • The ongoing increases in obesity and diabetes would be counteracted. • More people would be fitter and have greater muscle strength. • The number of cases of cardiovascular disease would go down, as would the number of heart attacks and strokes. • In theory the number of falls would go down, as well as incidences of osteo­ porosis and fractures in elderly people. • Elderly people and younger people alike would see an improvement in both learning and cognition, and their risk of dementia would be lowered. • The mental health effects would be numerous. Fewer and milder cases of depression and less stress-related ill health with anxiety and burnout.

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HOW DO WE GET MORE PEOPLE TO EXERCISE? Getting more people to be physically active is a major challenge, particularly for healthcare services. Although many of society’s various institutions – e.g. schools, workplaces, Parliament – are responsible for changing lifestyle habits, it is healthcare services that are responsible for encouraging patients with risk factors or with established diseases to perform physical activity (secondary prevention).9 There is no doub that patients receiving healthcare would benefit from increased physical activity. But the question is how to go about changing lifestyle habits, increasing physical activity and at the same time making this an obvious part of healthcare services. There are several tried-and-tested methods, but there is a clear lack of methods that are truly effective in getting patients to increase their physical activity. The traditional method has been to offer information and advice during conversations with patients, but this has had a limited effect. So-called exercise referral

schemes have been trialled, in which patients have been referred to gyms or similar to start exercising. This method has been used in Denmark and the United Kingdom, but it has proven to have an ambiguous effect in the studies that have been performed. A relatively new method – which has also been promoted by the Swedish National Board of Health and Welfare – is to offer individually adapted advice in combination with tools such as a pedometer, a diary or a prescription. There is also a structured follow-­ up. This method bears a strong resemblance to the Swedish FaR model (Fysisk aktivitet på recept – Physical Activity on Prescription).10 A systematic over­view study appeared in 2018, showing that there is strong scientific evidence that the FaR model increases physical activity levels. It is thought to be successful because it is adapted to the individual, which offers greater scope for changing bad lifestyle habits. There are discussions within the EU as to whether the FaR model should be the leading preventative method.

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PROSTATE CANCER, TREATMENT AND PHYSICAL ACTIVITY It is desirable to increase physical activity in patients with a destructive lifestyle, where their level of physical activity is so low that there is a risk it will worsen their disease.5 This could be patients who are obese, or who have diabetes, cardiovascular disease, a long-­ term pain condition or a psychiatric diagnosis. Patients with metastatic prostate cancer also have a lot to gain from changing their lifestyle and increasing their level of physical activity – improved quality of life and a longer life being just two examples.11 These patients have a great need for symptom-alleviating treatment, and around 20–30 % of those with prostate cancer are being treated with androgen deprivation therapy using GnRH analogues. The treatment lowers the levels of testosterone and increases survival to the same extent as surgical castration. However, androgen deprivation therapy has a negative effect on the body in a number of ways. The composition of the body changes (increased weight, reduced muscle mass and increased fat mass), and there is a deterioration in physical function, bone

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health and quality of life. There is also an increased risk of cardio­vascular disease.12

sexual function. Naturally, many experience a considerable deterioration in quality of life.

It is worth noting that the metabolic effects of androgen deprivation therapy differ from the changes normally seen in the metabolic syndrome. High-density lipoprotein (HDL) increases in patients undergoing androgen deprivation therapy, as does fat mass. It is primarily under the skin that fat mass increases, and not as much round the organs. Neither does blood pressure noticeably increase. The other metabolic effects of androgen deprivation therapy resemble those of the metabolic syndrome: increased total cholesterol and increased triglycerides, as well as increased insulin resistance and risk of diabetes. In addition, muscle strength and bone density decrease. All these changes appear early in the treatment, within 6 months, and lead to greatly decreased functional ability. The risk of fractures increases, as does that of cardiovascular complications. The fact is that it is more common for patients with metastatic prostate cancer to die of cardiovascular disease than of the actual cancer. Patients also have difficulties with

This problem has also been noted in the European EAU-ESTRO-SIOG guidelines.13 These recommendations state that the side effects of the disease and its associated treatment give patients a reduced quality of life, both physically and mentally. Patients undergoing androgen deprivation therapy should benefit greatly from increased physical activity, since it would counteract many of the metabolic changes occasioned by the treatment. But this is not all. Increased mobility could improve patients’ quality of life and their physical abilities, and reduce low mood and depression. Physical activity should also be recommended to patients undergoing chemotherapy. Increased mobility could reduce their side effects and allow the patient to tolerate a higher treatment dose. It would at least improve the way they feel generally and their quality of life.

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PATIENTS WITH PROSTATE CANCER HAVE A LOT TO GAIN FROM EXERCISE More physical activity in patients with prostate cancer undergoing androgen deprivation therapy could counteract most of the complications of the treatment. Common complications are impaired body composition, cardiometabolic risk factors, decrease in physical function, bone density and quality of life.

THE SCIENTIFIC EVIDENCE IS STRONG. PATIENTS WITH PROSTATE CANCER UNDERGOING ANDROGEN DEPRIVATION THERAPY HAVE THE FOLLOWING TO GAIN FROM PHYSICAL ACTIVITY: • Body composition is affected through a reduction in fat mass and loss of weight. If the person then increases their regular physical activity, it increases the chances of them maintaining a healthy weight. • Medium-intensity aerobic physical activity leads to: lower levels of bad cholesterol (LDL), lowered triglyceride levels, reduced insulin resistance and thus reduced risk of diabetes. Strength training also has an effect on insulin resistance and blood sugar. • When it comes to blood lipids, more intensive aerobic physical activity has the greatest effect. • Improved bone density may reduce the risk of fractures. This can be achieved with regular physical activity such as skipping and jumping.

The European guidelines recommend a change in lifestyle prior to androgen deprivation therapy.13 Patients should increase their physical activity, stop smoking, drink less alcohol and achieve a normal-­ level BMI. There are several studies currently investigating what effect physical activity has with regard to diabetes and cardiovascular disease on patients with prostate cancer undergoing androgen deprivation therapy. The effects of physical activity on certain metabolic parameters has been investigated previously. But, here too, more research is needed. None­theless, it may be concluded that physical activity has many positive effects in these patients. The challenge is compliance, i.e. motivating patients to get more exercise and then to persevere with it. If this can be achieved, we can say with certainty that positive effects will materialise.

• Regular physical activity also has many positive effects on the brain, improves mood, and reduces the risk of anxiety and self-perceived stress. It makes it easier to perform better as well, both at work and in everyday life.

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WHAT SHOULD YOU REMEMBER? As there are certain risks associated with exercise, it should be tailored to the individual. The initial basis is the ideal activity, or “the ideal prescription”, where a specific risk factor or disease is counteracted. The prescription is then adjusted according to the patient’s other diseases, medication, motivation and interest, as well as their current level of performance.

Patients with prostate cancer who are undergoing GnRH analogue therapy often develop osteoporosis. Bone mineral density deteriorates, increasing the risk of fractures. This obviously affects the degree to which the patient can be physically active. One way to be a little more certain is to perform a DEXA scan, which measures body composition.

According to the national recommendations, medium-­ intensity aerobic physical activity in combination with strength training is a good goal. The time it takes patients to achieve this goal varies, and much depends on how ill they are, their basic constitution, their motivation and their medication.

Medium-intensity aerobic physical activity provides considerable health benefits, at the lowest risk. If strength training is also performed using small weights and numerous repetitions, it is possible to limit the risk of injury. REMEMBER THE FOLLOWING RISKS: • If a person has fragile bones, mechanical overload can lead to fractures. • The risk of triggering a cardiovascular event in someone with a high risk profile or underlying, possibly subclinical, cardiovascular disease.

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Since many patients have cardiovascular disease or a high risk of being affected by it, an assessment must be made as to whether the physical activity should be limited. If the risk is high, a heart scan can be performed, as well as a work test, before the patient starts any intensive training. Medium-intensity activity, on the other hand, has few risks while offering RECOMMENDATIONS FOR PATIENTS excellent health benefits. WITH PROSTATE CANCER UNDERGOING ANDROGEN DEPRIVATION THERAPY: So what is medium-intensity (aerobic) physical activity? • Regular aerobic physical activity (cardio­ Simply put, it is exercise vascular training) at a medium-intensity that makes a person out of level, at least 30 minutes per exercise breath but still able to session, five times a week speak. For some, a walk is enough to achieve this, • Strength training avoiding large weights, while for others it may be focused on lots of repetitions, twice a week dancing, cycling, jogging or gardening. Gardening actually has some similarities to strength training, when one considers all the lifting required. Monotonous and excessively heavy lifting should be avoided. Regular, individually adapted physical activity can, in essence, be considered obligatory for a patient with prostate cancer undergoing androgen deprivation therapy.

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PRACTICAL ADVICE There is so far no universal method for getting everyone with prostate cancer and undergoing androgen deprivation therapy to increase their physical activity. There are, however, promising studies in Denmark involving structured training as part of the rehabilitation process. Lessons learned from the Swedish FaR model also support this.14 In very basic terms, FaR is based on individual dosage and a structured conversation in which obstacles are identified, combined with ways to make physical activity easier. There is then a follow-up.

A. Assessment prior to exercise The most important factor for success is for patients to be motivated to change their lifestyle. Therefore, the first assessment includes an evaluation of the patient’s motivation. It is very important for the

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patient to have a good understanding of the benefits of exercise. Patient education and written information could be used to disseminate knowledge about physical activity for these patients. In addition, the patient should be asked whether any other illness or medication could be an obstacle to physical activity. As mentioned previously, a DEXA scan can be performed to assess the body’s mineral density. The risk of cardiovascular complications should also be evaluated. So why is physical activity not prescribed to a greater extent? Doctors cite lack of time, lack of support from the organisation, lack of knowledge and inferior reimbursement mechanisms as the primary reasons.15 Education is therefore important, as is a focus on guidelines to increase the possibility of changed lifestyle habits/physical activity being included in the treatment.

Patients with prostate cancer undergoing andro­ gen deprivation therapy have long been a forgotten risk group for whom increased physical activity has enormous potential. Just as it has for patients within psychiatry.

B. How to exercise? Early intervention with individual assessment, then training in consultation with a physiotherapist. This particular model has been successful in Denmark.16 A long-term strategy then needs to be worked out, perhaps based on the FaR model. It is worth mentioning that median survival is > 40 months and 25 % of these patients live for longer than 7.5 years.

C. How to follow up? Help can be found in quality registers, which allow the effects of treatment to be followed. For the registers to be reliable, important outcome variables, fitness, strength, quality of life and mental health are needed, although not mineral density or metabolic parameters. The quality registers can play an important part in increasing motivation within the healthcare sector to encourage patients to physical activity. Using them also contributes to evening out differences in the care services provided. Today there are several health apps that help to motivate people to do exercise. These may be useful. Many of these apps also collect clinical data in order to improve patient care.

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REFERENCES 1. Ng SW, Popkin BM. Time use and physical activity: a shift away from movement across the globe. Obes Rev 2012;13(8):659-80.

7. Katzmarzyk PT, Lee IM. Sedentary behaviour and life expectancy in the USA: a cause-deleted life table analysis. BMJ Open 2012;2(4).

10. Kallings L. Physical activity on prescription. Studies on physical activity level, adherence and cardiovascular risk factors. Karolinska Institute 2008.

2. Bassett DR, Schneider PL, Huntington GE. Physical activity in an old order Amish community. Med Sci Sports Exerc 2004;36:79-85.

8. Lindgren M, Börjesson M, Ekblom Ö, Bergström G, Lappas G, Rosengren A. Physical activity pattern, cardiorespiratory fitness and socioeconomic status in the SCAPIS pilot trial. Prev Med 2016;4:44-9.

11. Socialstyrelsen. Nationella riktlinjer för prostatacancer. 2015.

3. WHO. Global strategy on diet, physical activity and health. In. Geneva: WHO; 2004. 4. www.fyss.se 5. Socialstyrelsen. Nationella riktlinjer för sjukdomsförebyggande metoder. 2011. 6. Ekblom-Bak E, Olsson G, Ekblom O, Ekblom B, Bergstrom G, Borjesson M. The Daily Movement Pattern and Fulfilment of Physical Activity Recommendations in Swedish Middle-Aged Adults: The SCAPIS Pilot Study. PLoS One 2015;10(5):e0126336.

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9. Piepoli M, Hoes A, Agewall S, Albus C, Brotons C, Catapano A, Cooney M, Corra U, Cosyns B, Deaton C, Graham I, Hall M, Hobbs F, Lochen M, Löllgen H, Marques-Vidal P, Perk J, Prescott E, Redon J, Richter D, Sattar N, Smulders Y, Tiberi M, vander­ Worp H, vanDis I, Verschuren W, Binno S. 2016 Euro­pean guidelines on cardiovascular disese pre­ vention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology amnd Other Socities on Cardiovascular Disease Prevention in Clinical Practice. Eur Heart J 2016; 37:2315-81.

12. Busch-Ostergren P, Kistorp C, Bennedbaek FN, Faber J, Sönksen J, Fode M. The use of exercise interventions to overcome adverse effects of andr­ogen therapy. Nature Rev 2016;13:353-64. 13. Mottet N, Bellmunt J, Briers E, Bolla M, Cornford P, deSantis M, Henry A, Joniau S, Lam T, Mason MD, Matveev V, vanderPoel H, vanderKwast TH, Rouviere O, Wiegel T. EAU-ESTRO-SIOG Guide­ lines on Prostate Cancer. Prostate Cancer Update 2016:1-146.

14. Börjesson M, Arvidsson D, Blomqvist Å, Daxberg E-L, Jonsdottir IH, Lundqvist S, et al. Efficacy of the Swedish model for physical activity on prescription [Effektivitet av den svenska modellen för fysisk aktivitet på recept (FaR)]. Göteborg: Västra Götalandsregionen, Sahlgrenska Universi­ tets­sjuk­huset, HTA-centrum; 2018. Contract No.: Regional activity based HTA 2018:100. 15. Borjesson M. Promoting Physical activity in the ho­spital setting. Germ J Sports Med 2013;64: 163-6. 16. Schmidt MLK, Østergren PB, Cormie P, Ragle AM, Sønksen J, Midtgaard J. "Kicked out into the real world": prostate cancer patients' experiences with transitioning from hospital-based supervised exercise to unsupervised exercise in the community. Support Care Cancer. 2018. [Epub ahead of print]

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IN PARTNERSHIP WITH Peter Busch Østergren MD, PhD Department of Urology Herlev and Gentofte Hospital Denmark Anne-Mette Ragle Physiotherapist Department of Occupational- and Physiotherapy Herlev and Gentofte Hospital Denmark Mats Börjesson Professor, Chief Physician Sahlgrenska University Hospital/Östra & Institute for neuroscience and physiology & CHP, Gothenburg University Sweden Olof Akre Professor, Chief physician Urology Patient area Pelvic Cancer Theme Cancer Karolinska University Hospital, Solna Sweden

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Anders Kjellman MD, PhD, Senior Consultant Patient Area Pelvic Cancer Theme Cancer Karolinska University hospital, Huddinge Sweden Markus Aly Assistant Chief Physician Urology, FEBU, PhD Patient area Pelvic Cancer Theme Cancer Karolinska University Hospital, Solna Sweden Andrea Porserud Specialist physiotherapist oncology Patient area Pelvic Cancer Theme Cancer Karolinska University Hospital, Solna Sweden

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