So You’re Gonna recommend exercise for men with prostate cancer (PCa) on ADT or chemotherapy

JOSEPH: Hi there and welcome. I’m Joseph Ischia. This podcast is from the team at Talking Urology where we are helping doctors and allied health practitioners develop a deeper understanding of the literature to ensure we apply the right evidence to the right patient. Continuing on this theme of getting right to the heart of the big urological issues, we thought we would exercise our cerebral muscles and get started on So You’re Gonna recommend exercise for men with prostate cancer (PCa) undergoing androgen deprivation therapy (ADT) and chemotherapy. Therefore, let me bring the literature to life with my very special co-host, who just happens to also suffer by being my wife, Dale Ischia.

DALE: Hello Joseph. It is a pleasure to be here. Right now, I could tell you more about improper fractions, colour shading and aboriginal history thanks to home schooling our kids, but I will refocus my thinking towards Exercise Oncology.

JOSEPH: Thanks for all your hard work there.

DALE: I am an accredited exercise physiologist from Melbourne, and we are going to tackle the topic, So You’re Gonna recommend exercise for men with prostate cancer undergoing androgen deprivation therapy and chemotherapy.

JOSEPH: I’ve already said that. It’s like you never listen to me.

DALE: Also, joining our co-host team will be accredited exercise physiologist and PhD candidate Ashley Bigaran from Australian Catholic University and the Baker Institute.

ASHLEY: Thanks Dale and Joseph. I feel like Joseph is about to be outnumbered by Exercise Physiologists…

DALE: He certainly will be. We will also be joined by Dr Eva Zopf. Eva is an exercise physiologist and completed her PhD in Exercise Oncology at the German Sport University in Cologne in Germany, did a postdoctoral research fellowship at Edith Cowan University in Perth and is now a key member of the Exercise Oncology team at the Australian Catholic University.

DALE: So, stay tuned while we give you all the latest news on using exercise to treat and manage the side effects of ADT and chemotherapy in men with PCa. As this podcast is all about exercise…
perhaps a few squats and push ups could be completed while enjoying the show!

JOSEPH: And indeed, we have a great podcast for you. So, Dale, let’s begin by talking about the first time you met Martin Gleeve.

DALE: When sitting next to Martin Gleeve at a dinner in Vancouver, he said to me; I know exercise is important for my patients, I always tell them to exercise and go to the gym; why would I send them to an Exercise Physiologist? I’m sure I came up with heaps of good points at the time, after I picked my ego up off the floor.
More recently, a client reported to me that his oncologist told him to go to the gym and push as hard as he can.
Yes, these doctors know what the research is saying, and the patient listens to their every word, but this general exercise advice could lead to injury or worse. We want these fellas exercising for the long haul, as ADT is typically a long-term treatment. Joseph, I assume you don’t have time to cover the intricacies of exercise prescription with your patients during your consults.

JOSEPH: No I certainly do not

DALE: Well, did you know there is a profession in the business of exercise that could make you look good by minimising the side effects of ADT and chemotherapy?

JOSEPH: Anything to make me look good Dale, tell me more.

DALE: I’m talking about my profession! Exercise Physiologist’s are the masterminds behind every effective exercise program. We individualise the exercise prescription by dose and mode of exercise e.g. aerobic exercise, weight or resistance training or balance training according to assessment findings. We comprehensively assess the patient’s medical history including comorbid and musculoskeletal conditions, medications, exercise history and side effects of treatment including chemotherapy induced fatigue and peripheral neuropathy leading to balance issues. We then test their cardiorespiratory fitness, recovery, current strength levels, balance and range of movement. We apply a holistic approach by taking note of the patients’ limitations and goals, then prescribe an exercise program using appropriate dose and mode of exercise. The dosage of exercise means we manipulate things like; intensity/load, frequency and duration of exercise. Recovery is also an important factor we can manipulate to optimise outcomes, this is particularly important when managing cancer related fatigue.

ASHLEY: A perfect introduction to our expertise. It’s important to note that exercise physiologists are governed by guidelines, similar to cancer treatment guidelines. Our new and improved exercise and cancer guidelines suggest all patients with cancer should be referred to an allied health professional including an accredited exercise physiologist.

DALE: These guidelines also recommend patients with cancer should complete a minimum of 30- 60 minutes of moderate aerobic exercise three times per week and at least two resistance training sessions per week.

ASHLEY: But what does this mean for men with prostate cancer? Let’s start off with a broader question for our resident expert. We asked Eva, if she were to prescribe an exercise program for men undergoing ADT and chemotherapy, what would it be?

EVA: So I think generally when we think about prescribing an exercise program for cancer patients we would always consider sort of what symptoms and treatment-related side effects these patients may be experiencing. However when we look at the research to date, it shows moderate to high intensity aerobic and resistance exercise as likely to provide sort of the greatest benefit to patients on ADT and chemotherapy and the reason being that sort of both those exercise modalities can target multiple body systems.

DALE: They are some excellent insights from Eva. Speaking of exercise…time to bring the exercise oncology literature to centre stage and discuss some of the standout randomised trials in this space.

ASHLEY: I’m really interested in the urologist perspective. Joseph, what side effects are you most concerned about when men are initiating ADT or chemotherapy?

JOSEPH: Good question. When I start a man on ADT or send them off for chemotherapy, there are so many side effects, but today I think we should focus on bone health, skeletal muscle, metabolic health and quality of life. So, my question for you is, how can we minimise these side effects? Do we just tell our patients to go for a run or lift weights?

ASHLEY: Haven’t you been listening to your wife? I think we should start the strongest evidence to date on body composition. Dale, it seems most exercise intervention trials have observed improvements in muscle strength but minimal changes in lean muscle mass. What may be causing this?

DALE: Absolutely. Factors that affect lean muscle mass outcomes include patient characteristics such as fitness, physical activity, diet as well as the duration of ADT. Trials have observed ~0.7kg increases in lean muscle mass following a combined aerobic and resistance training program or resistance training alone. Most exercise interventions vary across the trials but best muscle mass outcomes were achieved with the following formula: a combination of aerobic and resistance exercise training consisting of 12-6 repetition maximum at 2-4 sets completed 3 times per week for a minimum of 12 weeks. Although, there is still plenty of research required in this space!

JOSEPH: Geez, Dale. That sounds like some ideal fantasy world of exercise, right? We know that the perfect conditions in trials are often difficult to replicate in real life. How do you try to apply this to my everyday patient?

ASHLEY: Certainly it is a fantasy world, Joseph. We then asked Eva what type of exercise training should be prioritised to counteract the negative effects on body composition?

EVA: Patients receiving ADT often experience an increase in fat mass and a decrease in muscle mass, and I think the negative consequences of adiposity are well known but we’re also learning more and more about the importance of skeletal muscle, if we look at the current literature we see that loss of muscle mass can be significantly attenuated if we prescribe a structured and progressive resistance exercise component. To positively influence the increase in fat mass, the literature suggests that it’s likely that we have to prescribe a moderate to high intensity aerobic and resistance exercise program and including the aerobic exercises likely beneficial because it enhances fat metabolism and increases energy expenditure. We also have to keep in mind though that there are men with advanced prostate cancer that might experience cancer cachexia and here we would actually focus more on resistance exercise and minimize the continuous aerobic exercise to reduce energy expenditure. Lastly important to know is that if we can alter the body composition that also may favorably affect other treatment-related side effects such as cancer related fatigue.

JOSEPH: Yes, excellent insight from Eva. What about the cardiometabolic side effects of ADT? Ash, this is your PhD monster! Will these guys need to run marathons to reduce their cardiometabolic risk during ADT?

ASHLEY: Don’t give me any ideas…my program is hard enough. Key trials have evaluated markers of cardiometabolic health, but few have observed improvements beyond body composition. Our team believes the current exercise dose is suboptimal compared to other cancers and also non-cancer trials investigating cardiometabolic health outcomes.

DALE: Is the difference exercise intensity or frequency?

ASHLEY: Definitely. Exercise intensity is relatively low compared to non-cancer populations. There is a consistent lack of scientific evidence investigating longer exercise durations and higher exercise intensities on cardiometabolic health outcomes. We currently have a research trial underway that is directly addressing the impact of exercise on cardiometabolic health in men on ADT. A small plug – The EX-HEART trial is taking a break and will return after COVID-19 has left our shores.

JOSEPH: Thanks Ash. We look forward to the results of your study. Let’s move onto bone health. I am concerned about my elderly patients receiving ADT and/or chemotherapy, as this age group is particularly susceptible to osteopenia and osteoporosis. We have another great podcast coming out on bone health and ADT so stay tuned, but how can exercise affect bone health?

DALE: It’s remarkable how quickly ADT induces changes in the structural integrity of bone. In a large-scale randomised control trial investigating bone mineral density outcomes during ADT; around 37% of patients who were osteopenic at baseline were diagnosed with osteoporosis within one year. This almost doubled at the two-year follow-up.

JOSEPH: Those bones sound more brittle than my ego when you tell me I’m the 3rd best podcaster you know… in our house. But moving on. Has there been any major exercise trials published in this area recently, Dale?

DALE: Interestingly, only a few studies have observed favourable outcomes on bone density.

ASHLEY: Really? Why may this be the case? Are the exercise interventions too short or are studies not powered to detect changes in bone mineral density?

DALE: Exactly, Ash. For the first time, Newton and colleagues conducted a 12-month comparative effectiveness trial including different exercise modes on regional and whole-body bone mineral density. The authors concluded impact training (skipping, hopping, leaping and bounding ) and resistance training attenuated the decline in spine and hip bone density. The take home message was impact training and resistance training should be included in the exercise and cancer guidelines.

ASHLEY: Is it time to buy a skipping rope and some small hurdles for your patients, Joseph? They could definitely hop, skip and jump into your clinical consults.

JOSEPH: Finding a park outside my consulting rooms seems to be a small hurdle. In fact, I would love them to hop, skip or jump if it would help me stick to time.

DALE: It’s important to note that the majority of men starting out with an exercise program need to gradually build up to the point where they can withstand impact training. If I ask a 70 year old man to hop or jump during our first session I would be met with some choice words and cries of pain. Many have to overcome joint pain from osteoarthritis, or pelvic floor issues from a prostatectomy or radiation treatment, and I would need to make sure they aren’t at risk of a spontaneous fracture from bone metastases.

JOSEPH: Now, on this topic, I’m really curious about musculoskeletal impact loading and bone metastases in men on long term ADT and chemotherapy. I would have thought that these men have a relatively high risk of fractures due to the metastases. Is resistance training safe in men with bone metastases?

DALE: It’s interesting as most trials have excluded men with established bone metastases as they were deemed ‘unstable’ and the risk of fracture was extreme. Cormie and colleagues undertook a pilot study to determine the safety and feasibility of resistance training in men with established metastatic disease.

ASHLEY: For the exercise physiologists listening, it provided a systematic approach of prescribing exercise based on the location and extent of bone metastases and avoided sites with established metastatic disease.

DALE: Although this study had a small sample size and was a difficult group to recruit, this study really paved the way for exercise prescription in patients with bone mets.

ASHLEY: It sure did and it’s actually one of my ‘go to’ and favourite publications to date! We asked Eva about what advice she could you give exercise physiologists treating patients with established metastatic disease in clinical practice?

EVA: You really want to find out some information about the severity of the bone metastatic disease, the previous and current treatments that are used to manage the disease, any presence of osteoporosis, any history of sort of fractures or falls and then of course what disease and treatment-related side effects the patients may be experiencing such as bone pain, neurological symptoms or even muscle weakness. So with every sort of choice you make in every exercise prescription you would put together you always have to sort of think okay does the potential risk of an adverse event really outweigh the anticipated benefit towards the patient goals. So that’s really important to keep in mind. From everything we sort of know about this population and the multifaceted adverse events they experience, it’s likely that a multimodel exercise program involving aerobic, resistance but also balance exercises is likely to be beneficial. The program does need to be adapted if patients are at risk of experiencing a skeletal-related event so we want to focus on the controlled movements with correct form, we want to minimize the risk of falls, We want to avoid impact exercises if there’s a risk of fracture. We want to avoid or use caution with exercises that load the affected sites. Same with sort of rapid or loaded trunk rotations or flexions or extensions of the trunk, we would avoid those or limit at least how quickly we do them.

DALE: We then asked Eva, what should urologists or oncologists provide an exercise physiologist to assist with appropriate and safe program design?

EVA: It would be certainly helpful for an exercise physiologist to for example see a bone scan report because while patients may know their cancer stage and their grade requesting a bone scan report from the urologist can help provide insight into location, size and type of the bone lesion as well as the rate of progression and knowing whether a bone lesion is stable or unstable with regard to fracture risk as I mentioned before is key when developing a sort of safe exercise program.

JOSEPH: Excellent and thanks Eva for your insights. For urologists and oncologists listening, it sounds like we need to provide Exercise Physiologists with the bone scan results to assist with exercise safety. Another issue I’m concerned about is the impact their treatments have on their quality of life. What role can exercise play in improving the quality of life for men with PCa?

DALE: Not only does it improve their physical capacity to improve quality of life activities, such as gardening or picking up the grandkids, but patients readily report exercise is one thing they can do for themselves, it gives them a sense of control in an otherwise out of control situation. The psychosocial benefits of being in a group environment may include a stronger sense of belonging, control and ownership of tackling the side effects of their treatment. We asked Eva about the novel evidence being conducted in improving the quality of life and limiting psychological distress associated with their PCa experience as a result of exercise training.

EVA: There are actually a couple of trials that have been conducted that evaluated changes in mental health in men with prostate cancer and also undergoing ADT. Most of these trials have looked at sort of mental health outcomes as a secondary endpoint. We are currently running a trial that might be the first RCT that is specifically designed to examine the impact of exercise on the psychological side effects of prostate cancer and these are only including men that are actually experiencing psychological distress and the design of this trial is based on a finding we made suggesting that masculine self-esteem is a significant factor contributing to psychological health in men with prostate cancer. We believe that a group-based sort of exercise program may be a supportive service that men would find appealing and maybe a pathway to improve mental health in this patient population

JOSEPH: In summary, we understand the side effects of chemotherapy and ADT may compromise the quantity and quality of life in men with PCa. But Eva, what does the future hold for exercise oncology research in PCa?

EVA: There are so many open questions like can we counteract cardiotoxicity in patients undergoing ADT? What about cognitive function? What about sexual health? Can we prolong survival in these men? What exercise modality and intensity are the most appropriate for all these different outcomes and if we top that all with sort of the cancer treatments that are constantly changing, we always get to face new challenges and really exploring how exercise may for example improve treatment tolerance. I also think it’s important to mention implementation research. We are putting a lot of effort into conducting randomized control trials to prove the efficacy of exercise intervention and that’s really important work but we also have to facilitate sort of the translation of research into practice.

JOSEPH: What can a urologist tell their patients about exercise during ADT and chemotherapy?

DALE: Exercise is safe and feasible during ADT and chemotherapy. Referring to an exercise physiologist can help individualise exercise training to the patient’s treatment cycles, symptoms and side effects.

ASHLEY: What can an exercise physiologist tell their patients about exercising during ADT and chemotherapy?

DALE: Every program is targeted and specifically tailored to your baseline fitness, strength and current cancer treatment stage and treatment.

JOSEPH: OK, you’ve convinced me. SO now how can I refer my patients to an Accredited Exercise Physiologist?

ASHLEY: The website is https://www.essa.org.au/find-aep. You’ll be able to search by speciality e.g. cancer as well as post code. Patients can also access Medicare rebates for an Exercise Physiology appointment if they have been referred by their GP.

JOSEPH: And that’s everything on exercise for men with PCa on ADT and chemotherapy. Hopefully, you’ve learned a thing or two about the importance of exercise during and following treatment and perhaps reinstating that gym membership. So, let’s run through the fast five facts:
1. Exercise can increase lean muscle mass by ~2% and reduce fat mass by ~2-3% after a longer exercise intervention
2. Exercise can minimise ADT-induced bone mineral density loss but only when impact training was completed in conjunction with resistance training
3. Exercise can be systematically prescribed to patients with widespread bone mets and improve muscle strength (~11%), ambulation (~12%) and lean mass (~3%), respectively
4. Exercise can help reduce psychological distress and improve mood, especially when undertaken in a group-based environment

JOSEPH: Again, many thanks for listening. Thank you to Dale, Ashley Bigaran, and Eva Zopf for sharing her invaluable expertise and insights with us today. You can now get all our podcasts on iTunes or on twitter @talking_urology. Remember to send all feedback to feedback@talkingurology.com.au

You’ve been listening to Joseph Ischia, Dale Ischia, Ashley Bigaran and Eva Zopf. Written by Ashley Bigaran, Dale and Joseph Ischia. Produced by Joseph Ischia and Cara Webb.

So you’re gonna, the practical urology podcast for those who love urology.

Disclaimer: This podcast was sponsored by AbbVie Pty Ltd, which has no control over audio content. The content is entirely independent and based on published studies and experts’ s opinion. The views within the podcast do not necessarily reflect those of AbbVie Pty Ltd.