HELP YOUR PATIENTS TO BE PHYSICALLY ACTIVE by Astellas Nordic

HELP YOUR PATIENTS TO BE PHYSICALLY ACTIVE

ONC_2019_0013_NC 09.2019

EXERCISE PROGRAMME FOR MEN WITH PROSTATE CANCER UNDERGOING ANDROGEN DEPRIVATION THERAPY

FOREWORD Androgen deprivation therapy is the standard treatment offered to men with metastatic prostate cancer. This treatment is associated with a number of side effects, both physical and mental, including reduced quality of life, increased fatigue, loss of muscle strength and loss of bone mineral density. The treatment has also been shown to be associated with an increased risk of typeÂ 2 diabetes, cardiovascular diseases and bone fractures. One option that may help in mitigating the side effects listed above is to provide guidance on physical activity and exercise. This is also recommended in the relevant European (EAU) guidelines. Doing so makes great demands of those health professionals who are responsible for the treatment of men with advanced prostate cancer.

NEXT and this booklet offer a brief summary of the side effects associated with androgen deprivation therapy, and of how physical activity and exercise can benefit patients and treat these side effects. NEXT focuses on strength training and can be used as a guide for a supervised exercise course, or as a guide for individual exercise if supervised exercise is not an option locally. As a starting point, we recommend that all men with prostate cancer who undergo androgen deprivation therapy begin a supervised exercise course in order to learn how to exercise correctly and avoid injury, particularly if the disease has spread to the bones. The aim of NEXT is to make it easy to incorporate exercise as an active treatment option. We wish you all the best with NEXT.

CONTENTS BACKGROUND

WHAT CHALLENGES MIGHT THERE BE?

PATIENT ASSESSMENT CHART

FOLLOW-UP CHART

REFERENCES

BACKGROUND Can physical activity prevent the development of prostate cancer? From a health perspective, there is a lot to gain from regular physical activity. In the field of cancer treatment, research is being conducted into the use of physical activity and exercise as a preventative therapy, as a means of countering therapy-related side effects, as rehabilitation therapy and as a tool for improving quality of life. In connection with prostate cancer, the hypothesis is that physical activity can reduce the incidence of prostate cancer and improve prognoses by influencing the immune system and by lowering oxidative stress.1 There is a large quantity of published material in the area, including several studies which indicate that physical activity has a beneficial effect in lowering the risk of developing prostate cancer and as a treatment to improve the prognosis in patients who have already been diagnosed with it. The results, however, are not robust enough to present definitive conclusions in the area.1 Nonetheless, there seem to be good grounds for recommending physical activity to all men with prostate cancer, when the aforementioned study results are combined with

what we know about the generally positive effects of physical activity and exercise, and about its ability to counter the side effects of androgen deprivation therapy.2 The side effects of androgen deprivation therapy are described in more detail in the next section.

deprivation therapy has a negative effect on patients’ quality of life and on sexual and cognitive function. It is therefore no surprise that register studies have demonstrated an increased risk of developing type 2 diabetes, cardiovascular diseases and bone fractures associated with androgen deprivation therapy.2

Physical activity as a ‘pill’ for the side effects of androgen deprivation therapy

Physical activity is one of the very few active treatments that have been shown in randomised studies to be able to counteract some of the side effects mentioned above. Thus, the evidence indicates that physical activity can improve quality of life and reduce cancer-related fatigue in men with prostate cancer undergoing androgen deprivation therapy. In addition, physical activity has a positive effect on the metabolic changes, where its ability to reduce fat accumulation and increase muscle mass and strength are especially important.

Androgen deprivation therapy forms the basis of treatment for metastatic prostate cancer. It is also used as adjuvant therapy in connection with curative radiotherapy directed at the prostate in cases of locally advanced disease. In both scenarios, androgen deprivation therapy has proved to prolong survival and time to symptomatic progression. Despite its good effects, androgen deprivation therapy has a number of side effects, including metabolic side effects that involve a lowering of insulin sensitivity and changes to body composition (reduction of muscle mass and strength, as well as increased fat accumulation). Androgen deprivation therapy also causes increased decalcification of the bones, which can develop into osteoporosis. Moreover, androgen

Is all physical activity equally good? When we talk about the beneficial effect of physical activity, it is necessary to define the concept. How often and for how long should people exercise every week to achieve the desired effect, and at what intensity? Should exercise be done alone or in a group, supervised or unsupervised, and is one form of exercise, e.g. strength training, better than another? Good results can probably be achieved through many different kinds of sport and physical activity.

SIDE EFFECTS OF ANDROGEN DEPRIVATION THERAPY, AND HOW EXERCISE CAN COUNTERACT THEM Androgen deprivation therapy Fatigue

Fatigue

Quality of life

Muscle mass and muscle strength

Visceral and subcutaneous fat volume

Bone density

isk of type 2 diabetes, cardiovascular R disease and fractures

Libido and sexual function

Physical activity

Possibly

libido and sexual function

What matters is that the physical activity targets the desired results. In men with prostate cancer who are undergoing androgen deprivation therapy, the hope is to counteract especially the vulnerability that accompanies the loss of muscle strength, decreased quality of life and increased fatigue. Here the combination of fitness training and strength training seems ideal. This combination of exercise is also the best researched, and forms the basis for the recommendation of physical activity for men with prostate cancer undergoing androgen deprivation therapy in, for example, the European guidelines (EAU guidelines 2018).3 These recommend that all men with prostate cancer undergoing androgen deprivation therapy be offered 12 weeks of supervised exercise that combines fitness and strength training. In the Scandinavian countries, the general recommendation is for all men > 65 to be active for a minimum of 30 minutes daily (moderate intensity), combined with fit-

ness and strength training a minimum of twice a week (high intensity). The European guidelines also prescribe that the exercise should be supervised initially. There are several reasons for this. Generally speaking, compared with unsupervised exercise, supervised exercise as part of the treatment of cancer patients has proved to deliver better results in terms of both quality of life and physical function.4 In addition, supervised group exercise is the form of exercise that has been researched primarily, and it has proved to have a positive effect in men with prostate cancer undergoing androgen deprivation therapy. It is also important for these men to learn to exercise correctly in order to avoid injury. The primary concern is for bone fractures that can occur when men with bone metastases and possible osteoporosis undertake strength training.

EXERCISE RECOMMENDATIONS FOR MEN WITH PROSTATE CANCER UNDERGOING ANDROGEN DEPRIVATION THERAPY: 1. Be physically active for 30 minutes daily (moderate intensity) 2. Do fitness and strength training a minimum of twice a week (high intensity) 3. It is recommended that all be offered at least 12 weeks of participation in a supervised exercise course that combines fitness and strength training (EAU guidelines 2018) 4. Strength training should be performed using machines without the use of free weights in order to avoid injury in this patient group 5. The aim is a lifestyle change, so it is important to support continued exercise

WHAT CHALLENGES MIGHT THERE BE?

It takes motivation to start a course of exercise

Patients who are inactive must also be motivated

Most men with prostate cancer and their relatives have thought often about what they can do to improve life after the cancer diagnosis. But it can take a long time to put those thoughts into action, and many people want to have concrete advice from health professionals. It is therefore important for the healthcare team at the department where the patient receives treatment to be prepared, to know what exercise options are available locally or at the hospital, and to ask the patient about their wishes and motivation. Some patients also need a little push from a health professional, in the form of recommendations and guidance concerning exercise, in order to get going.

Patients who are already active are the most easily motivated to start regular exercise and NEXT. They often already do some form of exercise, and can use NEXT to focus their exercise for optimal results. For men who are inactive, it may initially require more effort to get started, and then to implement lifestyle changes in the longer term. It is important to note that those men who experience the greatest fatigue due to their cancer and the androgen deprivation therapy are the ones who gain the most from becoming physically active.5

CHALLENGES: • Practical barriers: • Lack of established exercise options specifically for men with prostate cancer • Large geographical distances for taking part in a supervised course • Not having a training partner • Insufficient motivation: • Lack of familiarity with exercising at a gym • Fatigue and lack of energy • Uncertainty regarding own ability to take part in an exercise course • Making a distinct lifestyle change and maintaining an active lifestyle

How can patients be motivated to maintain their learned exercise skills? For many patients it is hard to get started with exercise. Once past this, the positive effects of exercise on day-to-day energy levels and the feeling of improved general wellbeing, in particular, will support continued motivation to exercise. Having a regular training partner, be it a wife, a friend or a fellow patient from the supervised exercise course, can also help to develop regular exercise habits. For some patients, it may help to monitor improvements using a variety of physical tests and exercise objectives (see the objectives chart on page 14). It is also a good idea to discuss any challenges or worries that might arise in connection with exercising on one’s own as part of the general monitoring process for prostate cancer.

• Disease that limits opportunities for exercise

Exercise has to be modified for this patient group Exercise is for everyone. However, for some patients the exercise has to be adjusted in order to avoid injury. For men with prostate cancer undergoing androgen deprivation therapy, this applies particularly to those with multiple bone metastases or osteoporosis, since weight-bearing exercise can result in bone fractures. It is therefore recommended that this patient group be offered strength training with a focus on lower weights and more repetitions (see the modified exercise programme in the patient material). Generally speaking, strength training is not recommended for men with pain caused by bone metastases that requires analgesics. Moreover, all weight-bearing exercise should be performed on machines without the use of free weights. There will also be some men with prostate cancer who have cardiovascular diseases in addition. In this group, the intensity of fitness training should be adjusted to avoid unnecessary strain on the heart.

PATIENT ASSESSMENT CHART Assess, together with the patient, whether he needs the NEXT exercise programme by answering the following questions. The patient (tick if yes): Has prostate cancer Is undergoing androgen deprivation therapy Has a day-to-day function level that permits independent exercise on machines If the answer to all points above is yes, then the patient may benefit from the NEXT programme (preferably a supervised course).

Exercise caution if the patient has (tick if yes): Pay particular attention to the following when fitness and strength training are recommended for men with prostate cancer undergoing androgen deprivation therapy:

Known cardiovascular disease

• Multiple/larger bone metastases

Multiple/larger bone metastases

• Osteoporosis • Known cardiovascular disease

Osteoporosis

If the answer to the above is yes, exercise must be undertaken with caution (see the modified programme), with reduced intensity in cases of known cardiovascular disease and lower weights in cases of osteoporosis and multiple bone metastases. Weight-bearing exercise is not recommended in the case of painful bone metastases.

Generally speaking, weight-bearing exercise is not recommended for men with prostate cancer and bone metastases that require analgesics.

FOLLOW-UP CHART

How would you assess your overall quality of life this past week? Circle the most appropriate number. At the start:

It is important to note whether the patient improves or maintains the beneficial effects of exercise. The chart below can help in monitoring the effects of exercise and can be used as a form of motivation.

BODY MEASUREMENTS

At the start

After 12 weeks

After 24 weeks

After 48 weeks

Excellent

After 12 weeks: Very bad

Very bad

Waist measurement (cm)*

After 48 weeks:

Hip measurement (cm)** At the start

After 12 weeks

After 24 weeks

After 48 weeks

30-second sit-to-stand test (number)***

Very bad

Were you fatigued? Circle the number that best matches how you have felt over the past seven days.

Average number of steps (past week)**** Own tests*****

*Measure round the stomach between the hipbone and the bottom rib. **Measure the widest part of the hips at the top of the thighbone. ***The number of times you can rise from a chair and sit down again in 30Â seconds without using your arms. ****Measure using a pedometer (possibly a mobile phone app). *****Here your own tests and measurements can be inserted.

After 24 weeks:

Weight (kg)

PHYSICAL FUNCTION

Very bad

Not at all

A little

Somewhat

A lot

At the start

After 12 weeks

After 24 weeks

After 48 weeks

REFERENCES 1. Brookman-May SD, Campi R, Henriquez JDS, Klatte T, Langenhuijsen JF, Brausi M, et al. Latest Evidence on the Impact of Smoking, Sports, and Sexual Activity as Modifiable Lifestyle Risk Factors for Prostate Cancer Incidence, Recurrence, and Progression: A Systematic Review of the Literature by the European Association of Urology Section of Eur Urol Focus 2018. [In press] 2. Østergren PB, Kistorp C, Bennedbæk FN, Faber J, Sønksen J, Fode M. The use of exercise interven tions to overcome adverse effects of androgen deprivation therapy. Nat Rev Urol 2016;13:353–64.

4. Buffart LM, Kalter J, Sweegers MG, Courneya KS, Newton RU, Aaronson NK, et al. Effects and moderators of exercise on quality of life and physical function in patients with cancer: An individual patient data meta-analysis of 34 RCTs. Cancer Treat Rev 2017;52:91–104. 5. Taaffe DR, Newton RU, Spry N, Joseph D, Chambers SK, Gardiner RA, et al. Effects of Different Exercise Modalities on Fatigue in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: A Year-long Randomised Controlled Trial. Eur Urol 2017;72:293–9.

3. Bourke L, Smith D, Steed L, Hooper R, Carter A, Catto J et al. Exercise for Men with Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol 2016;69:693–703.

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

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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