Dr Ric Milner

Studies are increasingly showing that appropriate exercise is a valuable aid in helping reduce the risk of acquiring cancer, and improving outcomes during and after treatment, writes Dr Ric Milner*. Following diagnosis with metastatic prostate cancer, Dr Milner began “to explore the benefits of exercise and the appropriate application of exercise with cancer”.

Ric Milner’s personal story can be read here.

Although it is relatively early days in assessing the value of exercise as a therapy for cancer and treatment related conditions, there are significant signs that the body can, and generally does, react positively to appropriate physical activity.

Moreover, planned exercise and increased leisure time activity have also been shown to reduce the incidence of cancer.

Among the many benefits identified by researchers are an increased tolerance to chemotherapy and radiotherapy.

From a meta-analysis of new evidence in relation to exercise, diet and cancer (1), 2·5 hrs per week of moderate-to-vigorous activity showed 13% reduction in cancer mortality in the general population ‘before diagnosis’. In the same population, 15 metabolic equivalents of task (MET) hrs per week of physical activity showed 27% lower risk of mortality from cancer. (By definition, one MET is the energy required to sit still. Moderate activity is classified three to six METs. Vigorous activity is over six METs).

The same review (1) showed that post-diagnosis physical activity has stronger associations with mortality risk reduction (about 14% greater reduction in risk) than pre-diagnosis activity. In cancer survivors undertaking 15 MET hrs per week after diagnosis, the mortality risk from cancer decreased by 35%.

A systematic review (2) demonstrated that new data supported previous findings. For people who were more physically active, results showed a lower relative risk of cancer recurrence, cancer mortality, and all-cause mortality in breast and colorectal cancer.

Monga et al (8) showed an 8-week cardiovascular exercise program in patients with localized prostate cancer undergoing radiotherapy improved cardiovascular fitness, flexibility, muscle strength, and overall quality of life and prevented fatigue.

In another study, beneficial effects were noted when comparing a higher with a lower intensity exercise program, with significant treatment effects on reducing symptoms only among women in the higher intensity aerobic exercise program, or with the higher intensity program that combined aerobic and resistance exercise.

Exercise and adverse treatement effects

Apart from mortality benefits there are specific benefits from exercise to patients with conditions arising from their treatment. These include:

Bone health

In the systematic review (2), 7 trials were evaluated and showed mixed findings with some showing no benefit from weight training exercise in terms of bone health. One randomised controlled trial (RCT) (8) showed thrice weekly resistance training during 6 months of radiotherapy for spinal metastases showed significantly improved spine bone density compared with passive physical therapy.

Sexual Health

Sexual health outcomes were reviewed (2) in 6 studies: 3 in breast cancer and 3 in prostate cancer. Again, the review showed mixed results.

For breast cancer, one RCT for post treatment breast cancer patients showed improved scores for sexual activity and sexual pleasure with combined cognitive behavioural therapy and a 12-week home-based exercise program. In another study, no significant difference was seen by an intervention either during or after radiotherapy.

For patients with prostate cancer receiving androgen deprivation therapy, a 3-month program including aerobic and resistance exercise improved sexual function scores. However, another study with supervised walking sessions per week had no effect on sexual health among patients with prostate cancer post-surgery.

Fatigue and Muscle weakness

For symptoms associated with cancer and its treatment, fatigue has the best evidence of a significant beneficial effect from exercise. All three major studies of patients fatigued by chemotherapy showed a significant benefit from exercise.

Patients with cachexia have great trouble maintaining muscle mass as well as fat deposits. Exercise is the only strategy that has been shown to have any effect on reducing muscle mass decline with cachexia.

A study of biomechanical function of men (3) with prostate cancer who are treated with androgen depletion therapies (ADT) showed muscle loss patterns that are not consistent across all muscle groups. The study demonstrated a reduction in peak torque of hip flexors (14%) and knee extensors (16%). Specifically, iliopsoas, quadriceps and soleus function were affected.  Over time this results in a wider based gait and increase rates of falling.

Exercise programs probably need to target these muscles specifically although there are no studies yet to show this strategy works.

Cognitive health

Two of 5 studies reviewed (2) showed significant improvements in cognitive function, including an 8-week aquatic exercise program conducted post treatment for breast cancer, and a 4-week once weekly cycle “ergo” program for patients with breast or prostate cancer.

Psychological distress

Ten meta-analyses (2)  showed significant improvements in one or more of psychosocial outcomes among cancer survivors randomized to exercise compared with those randomized to a comparison group. Two studies did not show benefit.

Bowel and bladder function

Exercise resulted in significant improvements in bowel and bladder outcomes in 2 of 5 trials. One was a  6-week yoga intervention that improved constipation in breast cancer survivors post treatment. The other was a twice weekly resistance, flexibility, and kegel exercise intervention in elderly patients after radical prostatectomy for prostate cancer.
Body image/sleep etc.

Cormie et al (2) reported on their meta-analysis findings regarding body image, sleep, physical function, physical health, and shoulder dysfunction. They concluded  “With few exceptions, the conclusions of several meta-analyses are that exercise does have a significant positive effect on these outcomes”.

Quality of life

3 of the 4 meta-analyses findings (2) in breast cancer, and 2 which focused on haematological malignancies, reported significant improvements in quality of life for cancer survivors who exercised compared with those randomized to a comparison group. Evidence did not support a positive effect of exercise on quality of life in prostate, lung, colorectal, or gynaecological cancer survivor.

Immune Therapy and Exercise

Interestingly in the era of immune therapies it seems that the benefit of exercise is probably via immune changes. Using mouse models, Idorn et al (4) demonstrated that “voluntary exercise leads to an influx of immune cells in tumours, and a more than 60% reduction in tumour incidence and growth”.

It appears there is evidence that data is accumulating (4) “to suggest that patients whose tumors are characterized by a brisk infiltration of immune cells are more likely to respond to treatment”. As a result of this information, there is interest in “methods by which tumours with limited or absent immune cell infiltrates, i.e., “cold tumors” can be turned into “hot” tumors with an infiltration of anti-tumor immune cells, T cells, NK cells, dendritic cells, etc”.

In addition, “exercise prior to PD-1 therapy could represent a tool that condition patients to immunotherapy by increasing the immune infiltrate in the tumor, and in turn increase the chance for clinical response”.

Evidence (4) points at the immune system as being crucial also for the efficacy of chemotherapy. If substantiated by human studies, exercise could play a role by improving the immune response to conventional chemotherapy treatments.

Safety first

Many of the recommended exercise programs involve weight training as well as aerobic processes. The problem of weight training in a patient with metastatic disease in bones, is the risk of fracture. There have been several tools developed to try to assess this risk but they have been shown to be inaccurate.

Patients therefore need to start their weight training with low weights and gradually increase the load to gain the benefits. If a patient develops pain whilst doing the loaded exercise, he or she should reduce the load and seek advice from their medical team.

This is particularly important if a previously pain-free exercise becomes painful. The site of the pain then needs investigation.

There is also the risk that patients may feel that they have failed when the disease progresses despite their best efforts at exercise. The aim of treatment needs to be clear before embarking on an exercise program. The patients need to understand that exercise is not a cure, but an important adjunct to improving their chances of survival, and more importantly improving their quality of life.

When a patient’s cancer progresses despite surgery, chemotherapy, radiotherapy, immunotherapy or exercise, the therapy failed the patient, not the other way around.

*Dr Ric Milner is a Victorian GP of the Year, and has worked in a wide range of clinical roles. He is based at the You Yangs Medical Clinic, Lara, Victoria.

References

  1. Jacqueline Kerr, Cheryl Anderson, Scott M Lippman. Physical activity, sedentary behaviour, diet, and cancer: an update and emerging new evidence. Lancet Oncol 2017; 18: e457–71 https://www.ncbi.nlm.nih.gov/pubmed/28759385
  2. Prue Cormie*, Eva M. Zopf, Xiaochen Zhang, and Kathryn H. Schmitz. The Impact of Exercise on Cancer Mortality, Recurrence, and Treatment-Related Adverse Effects. Epidemiologic Reviews 00, 2017 https://www.ncbi.nlm.nih.gov/pubmed/28453622
  3. Ada S. Cheung, Hans Gray, Anthony G. Schache, Rudolf Hoermann, Daryl Lim Joon, Jeffrey D. Zajac, Marcus G.Pandy & Mathis Grossmann. Androgen deprivation causes selective deficits in the biomechanical leg muscle function of men during walking: a prospective case–control study. Journal of Cachexia, Sarcopenia and Muscle 2017; 8: 102–112 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5326829/
  4. Manja Idorn, Per thor Straten Exercise and cancer: from “healthy” to “therapeutic”? Cancer Immunol Immunother (2017) 66:667–https://link.springer.com/article/10.1007/s00262-017-1985-z
  5. Gao Yunfeng, He Weiyang, He Xueyang, Huang Yilong, Gou Xin. Exercise overcome adverse effects among prostate cancer patients receiving androgen deprivation therapy. Medicine (2017) 96:27 https://www.ncbi.nlm.nih.gov/pubmed/28682886
  6. Amy M Dennet, Casey L Peiris, Nora Shields, Delwyn Morgan and Nicholas F Taylor. Exercise therapy in oncology rehabilitation in Australia: A mixed-methods study. Asia-Pacific Journal of Clinical Oncology 2016 http://onlinelibrary.wiley.com/doi/10.1111/ajco.12642/full
  7. Tingting Li,Shaozhong Wei,Yun Shi,Shuo Pang,Qin Qin,Jieyun Yin,Yunte Deng,Qiongrong Chen,Sheng Wei,Shaofa Nie, Li Liu. The dose–response effect of physical activity on cancer mortality: findings from 71 prospective cohort studies. Br J Sports Med 2015;0:1– https://www.ncbi.nlm.nih.gov/pubmed/26385207
  8. Monga U, Garber SL, Thornby J, Vallbona C, Kerrigan AJ, Monga TN, Zimmermann KP. Exercise prevents fatigue and improves quality of life in prostate cancer patients undergoing radiotherapy. Arch Phys Med Rehabil. 2007 Nov;88(11):1416-22 https://www.ncbi.nlm.nih.gov/pubmed/17964881

Prostate Cancer - a personal account

In October last year I had a conversation with a friend of mine who lives in Ballina. He had recently been found to have a positive lymph node in the retroperitoneal space from his long-standing prostate cancer. He, like me, is a keen cyclist and I convinced him that as his disease was not curable that it was about time that he went riding with me in Italy. I had been bike riding at “Bike hotels” in Italy several times before, and had been trying to convince him that he should come to Italy with me for several years. 

He has had prostate cancer for more than 10 years but the finding of a positive node after radiotherapy convinced him that life is short and he should enjoy it so he agreed to ride with me in Italy. During this time several of my other bike riding friends became enthused and there are now 12 of us going at the end of August.

In February this year I developed chest pain and reluctantly attended accident and emergency for assessment. During the work up I was pleased to find that I did not have any evidence of cardiac disease but unfortunately there were sclerotic and lytic lesions seen in my thoracic spine on CT scanning.

Bone scanning revealed multiple lesions throughout my skeleton including my skull, maxilla and extensive disease in the pelvis and spine. There are also lesions in the long bones of both upper and lower limbs. I am pain free apart from the long-standing mechanical back pain that I have had since I was 17.

I had a PSA of 512 and have since had chemotherapy and androgen depletion therapy.

I gained weight and developed considerable oedema with chemotherapy and dexamethasone.

The dexamethasone was required to decrease the oedema associated with taxane chemotherapy but made me very hungry and grumpy and affected my sleep.

During the chemotherapy I maintained as much exercise as I could and I found that I had less symptoms of fatigue and slept better when I forced myself to get off the couch and do something. This was not an easy thing to do because the chemotherapy made me feel pretty terrible but my symptoms, even during the worst five days after each dose were diminished if I went for a short walk.

As the worst part of the chemotherapy wore off, I was able to continue riding and swimming, certainly not at the same level as before, but I felt both physically and psychologically considerably better.

Importantly I felt I had some control of this process that had been thrust upon me.

I began to explore the benefits of exercise and the appropriate application of exercise with cancer.

 I have read extensively and discussed concepts with an orthopaedic surgeon friend who has a special interest in cancer orthopaedics.

 An oncologist friend of mine has helped me find appropriate literature and this has been a fascinating and useful process for me.

Last week I rode 328 km mainly on a road bike, but some on a mountain bike.

 I swam 1 km twice and went to the gym for two sessions. The research and reading that I have done has helped me tailor my exercise regimen to be as safe and as effective as possible.

I feel much better without the chemotherapy and I am beginning to get a positive training effect from the exercise. During the chemotherapy my exercise ability gradually declined but I was still able to ride 70 km at a time but not at a fast pace.

The kindness shown to me by my bike riding friends deserves special mention. They waited for me and helped me by protecting me from the wind and tolerated my inability with “boy style” humour and good grace and love.

“ You’re riddled with cancer and as fat as a pig and your testicles are as big as peas but you still beat me up that hill you prick”

I really miss having testosterone for multiple reasons, not just the insult to my concept of myself as a sexual person, and my “manliness” and considered going back onto testosterone prior to my trip to Italy.

Training didn’t seem to be working much but I ceased chemotherapy about six weeks ago and I am at last gaining fitness again, albeit more slowly than when I did have normal levels of testosterone.

Having almost zero testosterone also results in moderate anaemia but this may take several more months before it becomes significant.

If I had not exercised throughout this process, I am certain that my quality of life would be hugely impacted by the treatment that I have a experienced.

I know that there is the potential to extend my life a bit with exercise but my main motivation is not the extension of my time on the planet but the maximising of my enjoyment of that time.

About Dr Ric Milner

Dr Ric Milner graduated from Monash University Medical School in 1977. His internship and following residency was at Geelong Hospital, southwest of Melbourne. The establishment of the Family Medicine Program by the RACGP occurred in 1973 and he undertook his medical training in General Practice under its auspices.

Dr Milner has been a supervisor for general practice registrars for more than 20 years, and he lectures in sexual health at Deakin University in Geelong.

Dr Milner chose a career in general practice, working at both Corio and Lara Community Health Centres, and later became a founding general practitioner at You Yangs Medical Centre in Lara, a suburb of the City of Greater Geelong.

He was involved in a collaborative project in the Geelong region to develop a process for initiating and completing advanced care directives from general practice. This has been the most successful advanced care plan process in Australia.

In his professional life he has been dedicated to the complex job of general practice as well as the areas of HIV medicine, venereology, ad drug and alcohol medicine. He has also been a doctor in the Victorian Prison system.

He is a board member of the Western Victoria PHN.

Dr Milner is a cycling enthusiast and rides at least 200 km per week. He follows a highly controlled medium load gym workout twice per week and averages one swim per week of around 1 km. He has been researching the benefits of exercise as an independent factor in the management of patients with cancer.

His award of Victorian GP of the Year for 2017 is a well-deserved honour.