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Article of the week: Immediate versus delayed exercise in men initiating ADT

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community, and a video produced by the authors. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

Immediate versus delayed exercise in men initiating androgen deprivation: effects on bone density and soft tissue composition

Dennis R. Taaffe*†‡, Daniel A. Galvão*, Nigel Spry*§¶, David Joseph***Suzanne K. Chambers*††‡‡§§, Robert A. Gardiner*¶¶***, Dickon Hayne†††‡‡‡Prue Cormie§§§, David H.K. Shum††¶¶¶and Robert U. Newton*†‡****

 

*Exercise Medicine Research Institute, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, School of Human Movement and Nutrition Sciences, University of Queensland, Brisbane, Queensland, §Genesis CancerCare, Joondalup, Faculty of Medicine, University of Western Australia, **Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, ††Menzies Health Institute Queensland, Griffith University, Gold Coast, ‡‡Centre for Research in Cancer, Cancer Council, Queensland, Brisbane, Queensland, §§Prostate Cancer Foundation of Australia, Sydney, New South Wales, ¶¶Department of Urology, Royal Brisbane and Womens Hospital, ***University of Queensland Centre for Clinical Research, University of Queensland, Brisbane, Queensland, †††UWA Medical School, University of Western Australia, Crawley, ‡‡‡Fiona Stanley Hospital, Murdoch, Western Australia, §§§Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria, Australia, ¶¶¶Neuropsychology and Applied Cognitive Neuroscience Laboratory, Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China, and ****Institute of Human Performance, The University of Hong Kong, Hong Kong, China

 

Abstract

Objectives

To examine whether it is more efficacious to commence exercise medicine in men with prostate cancer at the onset of androgen‐deprivation therapy (ADT) rather than later on during treatment to preserve bone and soft‐tissue composition, as ADT results in adverse effects including: reduced bone mineral density (BMD), loss of muscle mass, and increased fat mass (FM).

Patients and methods

In all, 104 patients with prostate cancer, aged 48–84 years initiating ADT, were randomised to immediate exercise (IMEX, n = 54) or delayed exercise (DEL, n = 50) conditions. The former consisted of 6 months of supervised resistance/aerobic/impact exercise and the latter comprised 6 months of usual care followed by 6 months of the identical exercise programme. Regional and whole body BMD, lean mass (LM), whole body FM and trunk FM, and appendicular skeletal muscle (ASM) were assessed by dual X‐ray absorptiometry, and muscle density by peripheral quantitative computed tomography at baseline, and at 6 and 12 months.

Results

There was a significant time effect (P < 0.001) for whole body, spine and hip BMD with a progressive loss in the IMEX and DEL groups, although lumbar spine BMD was largely preserved in the IMEX group at 6 months compared with the DEL group (−0.4% vs −1.6%). LM, ASM, and muscle density were preserved in the IMEX group at 6 months, declined in the DEL group at 6 months (−1.4% to −2.5%) and then recovered at 12 months after training. FM and trunk FM increased (P < 0.001) over the 12‐month period in the IMEX (7.8% and 4.5%, respectively) and DEL groups (6.5% and 4.3%, respectively).

Conclusions

Commencing exercise at the onset of ADT preserves lumbar spine BMD, muscle mass, and muscle density. To avoid treatment‐related adverse musculoskeletal effects, exercise medicine should be prescribed and commenced at the onset of ADT.

 

Editorial: Daily exercise is daily medicine

Memes such as #10000steps, #Fit4LIFE and Apple’s new #CloseYourRings demonstrate the mantra ‘exercise is medicine’, a cornerstone of modern medical advice. Taaffe et al. [1] in this issue of the BJUI discuss the value of exercise medicine – Immediate vs delayed exercise in men initiating androgen deprivation: effects on bone density and soft tissue composition.

Moving from anecdotal observation about exercise to actionable evidence has seen considerable progress recently. In the last 20 years, the biological rationale for the benefits of exercise through mechanisms of physiological adaptation has become better understood [2]. Benefits, comparable to some biopharma breakthroughs, have been demonstrated in cardiovascular, neurobiological and psychological health and disease. This is now equally true in oncology [3]. Researchers at the University of Glasgow in Scotland wanted to seek out out if glycerol could hydrate also as creatine and what would happen if they combined both ingredients. What they found was pretty astonishing! 24 participants were ran through a series of experiments over 7 days where they ingested either creatine or glycerol and where they ingested both glycerol plus creatine at an equivalent time. The researchers discovered the participants who took glycerol and creatine had almost 40% more fluid weight than the participants who only took creatine and nearly 50% more fluid than those that only took glycerol. Some people wonder if this fluid increase will have a “soft” look and therefore the answer is absolute not because the water increase from glycerol is usually within the blood. To be more precise it increases the quantity of plasma in your body. So if you would like to urge that hardcore, skin-tearing pump, combine them both in your pre-workout, shop stairmaster machines.

Since the stoma serves as a channel for the feces to be eliminated in the body, it is vital to maintain skin integrity surrounding it. Stoma skin barrier is being placed to the stoma to keep the ostomy bag kept in place. An ostomy bag is being connected to the barrier to collect body waste. Generally, ostomy procedure is being performed for greater efficiency during waste elimination. Most of these supplies are given as one package when you purchase it in pharmacies or medical stores.

In cancer surgery, it is intuitive that physical activity/exercise increases cardio‐respiratory fitness and the body’s adaption to physiological stress, hence reducing mortality and morbidity in the perioperative period. Buy Athletic Sports Tape Today for the best result in exercise and comfortable exercise.  Less obvious is how this phenomenon offers benefit to quality of life, morbidity, and survival. Recent understanding in biology helps link exercise and systemic fitness to cellular metabolism, immunological response, and mutagenesis. Discoveries in previously overlooked epigenetic, immunological, metabolic, and cell growth pathways; and more research, are leading to the inception of the new fields of metabolic oncology and exercise oncology [4]. There is a growing resource of therapeutic candidates in trials targeting novel metabolic pathways, induced also in exercise, improving cellular metabolic fitness to reduce the Warburg effect and immunosuppressive lactate in the tumour microenvironment [5]. Whether you’re a beginner or a seasoned lifter, there’s a workout plan for your goals. 

Several notable studies have looked at genetics, quantified cardio‐pulmonary measures of fitness, exercise pre‐habilitation/enhanced recovery, and survivorship programmes across many cancers including oesophageal, colorectal, and prostate cancer. The data suggest that exercise improves outcomes after surgery, quality of life, hospital admissions, progression‐free survival, and overall survival [6].

Prostate cancer is a special case often treated with androgen‐deprivation therapy (ADT), yet androgens are an essential factor in maintaining bone mineral density; muscle mass, as well as motivation to exercise/exercise capacity; and sexual health. Hormone chemotherapy compromises the key role of androgens in maintaining musculoskeletal health and fitness at a systemic and cellular level. This poses hazards. Aside from the longer term hope of targeted therapies to maintain exercise capacity with all of its biological adaptations, perhaps we can reduce some of the deleterious effects of ADT with exercise interventions. Together with behavioural, nutritional and pharmacological treatment pathways, we aim to augment the positive effect exercise brings to patients with prostate cancer, and patients with cancer more generally.

As our scientific understanding increases, it is clear that personalised, prescribed exercise pre‐habilitation is likely to become a ‘gold standard’ in oncology care. Many treatments may increase survival, but at a cost of quality of life; physical activity may not only extend life but may also enhance its quality. Pre‐habilitation warrants serious further study if it is to become widely adopted in practice. It is not simply about telling patients to keep active. As per the Silver and Baima [7] definition, it is ‘a process on the cancer continuum of care that occurs between the time of cancer diagnosis and the beginning of acute treatment, includes physical and psychological assessments that establish a baseline function level, identifies impairments, and provides targeted interventions that improve a patient’s health to reduce the incidence and the severity of current and future impairments’.

References

  1. Taaffe D, Galvão D, Spry N et al. Immediate versus delayed exercise in men initiating androgen deprivation: effects on bone density and soft tissue composition. BJU Int 2019123: 261–9
  2. Hojman P, Gehl J, Christensen JF, Pedersen BK. Molecular mechanisms linking exercise to cancer prevention and treatment. Cell Metab 201727: 10–21
  3. Cormie P, Zopf EM, Zhang X, Schmitz KH. The impact of exercise and cancer: systematic review of the impact of exercise on cancer mortality, recurrence and treatment related side effects. Epidemiol Rev 201739: 71–92
  4. Kinnaird A, Michelakis ED. Metabolic modulation of cancer: a new frontier with great translational potential. J Mol Med 201593: 127–42
  5. Vander Heiden MG. Targeting cancer metabolism: a therapeutic window opens. Nat Rev Drug Discov 201110: 671–84
  6. Thomas RJ, Holm M, Al‐Adhami A. Physical activity after cancer: an evidence review of the international literature. Br J Med Pract 20147: 16–22
  7. Silver JK, Baima J. Cancer prehabilitation: an opportunity to decrease treatment‐related morbidity, increase cancer treatment options, and improve physical and psychological health outcomes. Am J Phys Med Rehabil 201392: 715–27

Video: Immediate versus delayed exercise in men initiating androgen deprivation

Immediate versus delayed exercise in men initiating androgen deprivation: effects on bone density and soft tissue composition

Abstract

Objectives

To examine whether it is more efficacious to commence exercise medicine in men with prostate cancer at the onset of androgen‐deprivation therapy (ADT) rather than later on during treatment to preserve bone and soft‐tissue composition, as ADT results in adverse effects including: reduced bone mineral density (BMD), loss of muscle mass, and increased fat mass (FM).

Patients and methods

In all, 104 patients with prostate cancer, aged 48–84 years initiating ADT, were randomised to immediate exercise (IMEX, n = 54) or delayed exercise (DEL, n = 50) conditions. The former consisted of 6 months of supervised resistance/aerobic/impact exercise and the latter comprised 6 months of usual care followed by 6 months of the identical exercise programme. Regional and whole body BMD, lean mass (LM), whole body FM and trunk FM, and appendicular skeletal muscle (ASM) were assessed by dual X‐ray absorptiometry, and muscle density by peripheral quantitative computed tomography at baseline, and at 6 and 12 months.

Results

There was a significant time effect (P < 0.001) for whole body, spine and hip BMD with a progressive loss in the IMEX and DEL groups, although lumbar spine BMD was largely preserved in the IMEX group at 6 months compared with the DEL group (−0.4% vs −1.6%). LM, ASM, and muscle density were preserved in the IMEX group at 6 months, declined in the DEL group at 6 months (−1.4% to −2.5%) and then recovered at 12 months after training. FM and trunk FM increased (P < 0.001) over the 12‐month period in the IMEX (7.8% and 4.5%, respectively) and DEL groups (6.5% and 4.3%, respectively).

Conclusions

Commencing exercise at the onset of ADT preserves lumbar spine BMD, muscle mass, and muscle density. To avoid treatment‐related adverse musculoskeletal effects, exercise medicine should be prescribed and commenced at the onset of ADT.

View more videos

 

Article of the Week: The implications of baseline bone‐health assessment at initiation of androgen‐deprivation therapy for prostate cancer

Every Week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this month, it should be this one.

The implications of baseline bone‐health assessment at initiation of androgen‐deprivation therapy for prostate cancer

 

Peter S. Kirk* , Tudor Borza*, Vah akn B. Shahinian, Megan E.V. Caram§Danil V. Makarov**, Jeremy B. Shelton††, John T. Leppert‡‡§§, Ryan M. Blake*, Jennifer A. Davis§, Brent K. Hollenbeck*, Anne Sales§¶¶ and Ted A. Skolarus *§

 

*Dow Division of Health Services Research, Department of Urology, Division of Nephrology, Department of Internal Medicine, Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan Health System, §Veterans Affairs (VA) Health Services Research and Development, Center for Clinical Management Research, VA Ann Arbor Healthcare System, University of Michigan Medical School, Ann Arbor, MI, USA, Departments of Urology and Population Health, NYU Langone Medical Center, New York City, NY, USA, **VA New York Healthcare System, New York City, NY, USA, ††VA Greater Los Angeles Healthcare System, Los Angeles City, LA, USA, ‡‡Department of Urology, Stanford University School of Medicine, Stanford, CA, USA, §§VA Palo Alto Healthcare System, Palo Alto, CA, USA, and ¶¶Department of Learning Health Sciences, University of Michigan Medical School, Ann Arbor, MI, USA

 

Read the full article

Abstract

Objectives

To assess bone‐density testing (BDT) use amongst prostate cancer survivors receiving androgen‐deprivation therapy (ADT), and downstream implications for osteoporosis and fracture diagnoses, as well as pharmacological osteoporosis treatment in a national integrated delivery system.

Patients and methods

We identified 17 017 men with prostate cancer who received any ADT between 2005 and 2014 using the Veterans Health Administration cancer registry and administrative data. We identified claims for BDT within a 3‐year period of ADT initiation. We then used multivariable regression to examine the association between BDT use and incident osteoporosis, fracture, and use of pharmacological treatment.

Results

We found that a minority of patients received BDT (n = 2 502, 15%); however, the rate of testing increased to >20% by the end of the study period. Men receiving BDT were older at diagnosis and had higher‐risk prostate cancer (both P < 0.001). Osteoporosis and fracture diagnoses, use of vitamin D ± calcium, and bisphosphonates were all more common in men who received BDT. After adjustment, BDT, and to a lesser degree ≥2 years of ADT, were both independently associated with incident osteoporosis, fracture, and osteoporosis treatment.

Conclusions

BDT is rare amongst patients with prostate cancer treated with ADT in this integrated delivery system. However, BDT was associated with substantially increased treatment of osteoporosis indicating an underappreciated burden of osteoporosis amongst prostate cancer survivors initiating ADT. Optimising BDT use and osteoporosis management in this at‐risk population appears warranted.

Read more articles of the week

 

Editorial: Low rates of bone density testing in prostate cancer survivors on androgen‐deprivation therapy: where do we go from here?

In this month’s issue of the BJU International, Kirk et al. 1 describe their findings regarding an important issue in the care of prostate cancer survivors on androgen‐deprivation therapy (ADT): the underuse of bone density testing (BDT) to screen for osteoporosis. ADT is the commonest systemic therapy in patients with prostate cancer, used in both metastatic and localised settings. Whilst it has clear survival benefits, ADT is also associated with harms including cardiovascular, cognitive, and metabolic side‐effects, as well as an increased risk of osteoporosis and fractures. These bone‐related complications are costly from a quality‐of‐life and financial perspective, especially given the critical importance of mobility in maintaining performance status and cardiovascular health during cancer treatment 23. Consequently, most clinical practice guidelines include osteoporosis screening as a recommendation for men undergoing ADT.

In their study, ‘The implications of baseline bone health assessment at initiation of androgen‐deprivation therapy for prostate cancer’, the authors describe patterns of use of BDT and diagnosis of osteoporosis amongst men treated for prostate cancer in the USA Veterans Affairs (VA) system within a 3‐year period following ADT initiation. There was a statistically significant increase in the BDT rate throughout the study period; however, overall BDT remains uncommon amongst patients with prostate cancer on ADT, used in only 15% of men in their cohort. Unsurprisingly, patients who received BDT were more likely to be diagnosed with osteoporosis, be diagnosed with a fracture, and receive treatment with vitamin D, calcium and bisphosphonates. The authors acknowledge an important limitation about the applicability of their VA study to the civilian health population. However, given that the VA and military health systems perform as well, if not better, on several important metrics in prostate cancer care 45, these results should not be ignored simply because they were obtained in the military health system.

The increase in BDT screening throughout the study may be attributable to increased awareness of guidelines published during the study period. However, the overall BDT rate remains low. This may be explained by insufficient access, lack of information technology, as well as more nebulous aspects of care such as physician culture, beliefs, and habits 6.

Studies such as this are vital to identify opportunities for improving care delivery. What are needed next are innovations to optimise the delivery of care for patients treated with ADT. Whilst improving BDT adherence may lack the cachet of next‐generation targeted therapies, this is an example of the kind of simple, measurable area where improvement in care delivery systems may yield large benefits.

There are many possible avenues for success: quality improvement collaboratives are one well‐known innovation, which may be applicable to this area: examples, such as the Michigan Urological Surgery Improvement Collaborative (MUSIC) and the AUA Quality Registry (AQUA) are success stories, but to our knowledge there are no published studies specifically attempting to improve adherence to BDT guidelines within these cohorts. Other practice‐based innovations include navigators and multidisciplinary cancer teams, either of which may yield improvements in guideline adherence. Online patient support groups can raise awareness. And although we all know how electronic reminders have frustrated countless physicians, electronic reminders about recommended tests and interventions may be an important tool. At our institution, a Prostate Cancer Foundation grant is funding the development of a mobile health app, which is targeted exclusively at men receiving ADT for prostate cancer. This app will encourage physical activity and healthy eating, which can both support bone health.

In our view, the issue of bone screening is a clear example of where innovative strategies to improve care delivery and guideline adherence may make a big difference for men living with prostate cancer. We look forward to seeing more in the years to come.

 

Sabrina S. Harmouch, Alexandra J. Berger, and Alexander P. Cole

 

Center for Surgery and Public Health, Division of Urological Surgery, Brigham and Wo mens Hospital, Harvard Medical School, Boston, MA, USA

 

References
  • Kirk PS, Borza T, Shahinian VB et al. The implications of baseline bone‐health assessment at initiation of androgen‐deprivation therapy for prostate cancerBJU Int2018121: 558–64

 

 

 

  • Cole AP, Jiang W, Lipsitz SR et al. The use of prostate specific antigen screening in purchased versus direct care settings: data from the TRICARE® military databaseJ Urol 2017198: 1295–300

 

  • Cullen J, Brassell SA, Chen Y et al. Racial/Ethnic patterns in prostate cancer outcomes in an active surveillance cohortProstate Cancer 20112011: 234519

 

 

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