Resistance exercise in men receiving androgen deprivation therapy for prostate cancer

This thesis encompasses two literature reviews (chapter 2 & 3) and two experimental chapters (4 and 5) examining the available literature on exercise and cancer, resistance training and its anabolic responses in older men and women, the side effects of Androgen Deprivation Therapy (ADT) for prostate cancer and finally, the role of resistance exercise as a clinical intervention to counteract such changes as an adjuvant therapy

Exercise medicine for prostate cancer

Since initial reports in the mid-1980s, there has been increasing interest in the application of exercise as medicine for the prevention and management of cancer. A large number of high-quality, randomised, controlled trials with cancer survivors have confirmed both aerobic and resistance exercise to be highly beneficial for improving body composition, quality of life, mental health functional capacity and reducing risk of cancer recurrence and development of other chronic diseases. Such benefits have ultimately been realised in reduced cancer mortality between 30 and 60 % in large cohort retrospective studies. Treatments for prostate cancer are increasingly effective with quite high 5- and 10-year survival rates; however, side effects of endocrine treatments in particular impact on quality of life and increased co-morbidities for the survivor. Testosterone deprivation while highly effective for controlling prostate cancer growth results in loss of muscle and bone, increased fat mass, increased incidence of metabolic syndrome, cardiovascular disease and sudden death. Exercise has been demonstrated to be a very effective medicine for counteracting all of these treatment toxicities as well as improving mental health and quality of life. Exercise has been demonstrated to be safe and well tolerated by cancer patients. Current recommendation is to complete at least 150 min of aerobic exercise and two or more sessions of resistance training per week. More specific exercise prescription is required to address particular treatment toxicities such as bone loss or obesity. This paper is a review of key research from our group into exercise medicine for prostate cancer

Exercise medicine for advanced prostate cancer

Purpose of review: Exercise is a provocative medicine, known for its preventive, complimentary and rehabilitative role in the management of cancer. Impressively, exercise is also emerging as a synergistic and targeted medicine to enhance symptom control, modulate tumour biology and delay disease progression, with the potential to increase overall survival. Given the complex clinical presentation of advanced prostate cancer patients and their omnipresent comorbidities, this review describes the current and potential role of exercise medicine in advanced prostate cancer. Recent findings: Exercise has been shown to be safe, feasible and effective for advanced prostate cancer patients, inclusive of patients with bone metastases; a previously excluded population due to patient and clinician fear of adverse events. Preclinical data provide insight into the ability of exercise to modulate cancer-specific outcomes, may synergistically increase the potency of chemotherapy and radiotherapy and may endogenously and/or mechanically suppress tumour formation, growth and invasion in visceral and skeletal tissue. Epidemiological studies have also shown an association between physical activity and increased survival. Summary: Exercise oncology is rapidly evolving, with impressive possibilities that may directly improve patient outcomes in advanced prostate cancer. Research must focus on translating preclinical trials into human clinical trials and investigate the direct effect of exercise on overall survival

Exercise effects on muscle quality in older adults: A systematic review and meta-analysis

To systematically review and analyse the effects of exercise on morphological and neuromuscular muscle quality (MQ) outcomes in older adults and assess a range of possible moderators that may affect the impact of exercise on MQ outcomes. Using PRISMA guidelines, randomised controlled trials were searched in CINAHL, EMBASE, LILACS, PubMed, SciELO, Web of Science, MedNar, OpenGrey and OpenThesis databases. Eligible trials examined the effects of exercise interventions on morphological and neuromuscular MQ in older adults ( ≥ 60 years). Twenty-one trials (n = 973 participants) were included. Exercise significantly improved morphological MQ (effect size (ES) = 0.32, 95% CI 0.13–0.51, P \u3c 0.001) with significant results maintained for studies assessing muscle density and intermuscular adipose tissue (ES = 0.45–0.52, P \u3c 0.05). For neuromuscular MQ, exercise provided significant positive effects (ES = 0.49, 95% CI 0.29–0.69, P \u3c 0.001) but only maintained for physically healthy participants (ES = 0.43, P \u3c 0.001), resistance exercise interventions (ES = 0.64, P \u3c 0.001), or studies assessing 1-RM or knee extensor isokinetic muscle strength relative to leg lean mass (ES = 0.48–0.62, P = 0.001). Associations between exercise duration and changes in MQ measures were not observed (P \u3e 0.05). Supervised exercise interventions significantly improved different measures of MQ regardless of exercise duration, although these effects were small-to-moderate and not supported across all population-, exercise-, and methods-related features

Resistance exercise dosage in men with prostate cancer: Systematic review, meta-analysis and meta-regression

Purpose Resistance training (RT) improves an array of treatment-related adverse effects in men with prostate cancer, however, the minimal dosage required is unknown. We systematically reviewed the RT effects in prostate cancer patients to determine the minimal dosage regarding the exercise components (type, duration, volume, and intensity) on body composition, physical function, muscle strength, cardiorespiratory fitness, body mass index (BMI), and prostate-specific antigen (PSA). Methods Using PRISMA guidelines, MEDLINE, CINAHL, EMBASE, SPORTDiscus, and Web of Science databases were searched. Eligible randomised controlled trials examined prostate cancer patients undertaking resistance-based exercise programs during or following treatment. Meta-analysis was undertaken when more than 3 studies were included. Associations between mean differences and the exercise components were tested by univariate and multivariate meta-regression analysis. Results Twenty-four papers describing 22 trials and involving 1,888 prostate cancer patients were included. Exercise improved fat mass (-1% in body fat and -0.5 kg in fat mass), lean mass (+0.5 kg in lean and appendicular lean mass), functional capacity (i.e., chair rise, 400-m test, 6-m fast walk and stair climb tests) and fitness outcomes (i.e., VO2 peak and muscle strength) (P=0.040 - \u3c 0.001) with no change in BMI or PSA (P= .440 - .735). Meta-regression indicated no association between exercise type, RT duration, weekly volume and intensity and primary outcomes (P= .075 - .965). There was a significant association between RT intensity and chest press muscle strength (favouring moderate-intensity, P= .012), but not in other secondary outcomes. Conclusion In untrained older men with prostate cancer initiating an exercise program, lower volume at moderate-to-high intensity is as effective as higher volume RT for enhancing body composition, functional capacity and muscle strength in the short-term

The Exercise and Sports Science Australia position statement: Exercise medicine in cancer management

Objectives: Since Exercise and Sports Science Australia (ESSA) first published its position statement on exercise guidelines for people with cancer, there has been exponential growth in research evaluating the role of exercise pre-, during and post-cancer treatment. Design and Methods: The purpose of this report is to use the current scientific evidence, alongside clinical experience and exercise science principles to update ESSA’s position statement on cancer-specific exercise prescription. Results: Reported in this position statement is a summary of the benefits accrued through exercise following a cancer diagnosis and the strengths and limitations of this evidence-base. An exercise prescription framework is then proposed to enable the application of cancer-specific considerations for individualisation, specificity, safety, feasibility and progression of exercise for all patients. Additional specific exercise prescription considerations are provided for the presence of haematological, musculoskeletal, systemic, cardiovascular, lymphatic, gastrointestinal, genitourinary and neurological disease- and treatment-related concerns, as well as presence of co-morbid chronic disease. Further, we also identify and discuss cancer-specific pragmatic issues and barriers requiring consideration for exercise prescription. Conclusions: While for the majority, multimodal, moderate to high intensity exercise will be appropriate, there is no set prescription and total weekly dosage that would be considered evidence-based for all cancer patients. Targeted exercise prescription, which includes the provision of behaviour change advice and support, is needed to ensure greatest benefit (as defined by the patient) in the short and longer term, with low risk of harm

The potential role of exercise in neuro-oncology

Patients with brain and other central nervous system cancers experience debilitating physical, cognitive, and emotional effects, which significantly compromise quality of life. Few efficacious pharmacological strategies or supportive care interventions exist to ameliorate these sequelae and patients report high levels of unmet needs in these areas. There is strong theoretical rationale to suggest exercise may be an effective intervention to aid in the management of neuro-oncological disorders. Clinical research has established the efficacy of appropriate exercise in counteracting physical impairments such as fatigue and functional decline, cognitive impairment, as well as psychological effects including depression and anxiety. While there is promise for exercise to enhance physical and psychosocial wellbeing of patients diagnosed with neurologic malignancies, these patients have unique needs and research is urgently required to explore optimal exercise prescription specific to these patients to maximize safety and efficacy. This perspective article is a discussion of potential rehabilitative effects of targeted exercise programs for patients with brain and other central nervous system cancers and highlights future research directions

Pre-Altitude Serum Ferritin Levels and Daily Oral Iron Supplement Dose Mediate Iron Parameter and Hemoglobin Mass Responses to Altitude Exposure

Purpose : To investigate the influence of daily oral iron supplementation on changes in hemoglobin mass (Hbmass) and iron parameters after 2–4 weeks of moderate altitude exposure.Methods :Hematological data collected from 178 athletes (98 males, 80 females) exposed to moderate altitude (1,350–3,000 m) were analysed using linear regression to determine how altitude exposure combined with oral iron supplementation influenced Hbmass, total iron incorporation (TII) and blood iron parameters [ferritin and transferrin saturation (TSAT)]. Results :Altitude exposure (mean ± s: 21 ± 3 days) increased Hbmass by 1.1% [-0.4, 2.6], 3.3% [1.7, 4.8], and 4.0% [2.0, 6.1] from pre-altitude levels in athletes who ingested nil, 105 mg and 210 mg respectively, of oral iron supplement daily. Serum ferritin levels decreased by -33.2% [-46.9, -15.9] and 13.8% [-32.2, 9.7] from pre-altitude levels in athletes who supplemented with nil and 105 mg of oral iron supplement daily, but increased by 36.8% [1.3, 84.8] in athletes supplemented with 210 mg of oral iron daily. Finally, athletes who ingested either 105 mg or 210 mg of oral iron supplement daily had a greater TII compared with non-supplemented athletes (0 versus 105 mg: effect size (d) = -1.88 [-2.56, -1.17]; 0 versus 210 mg: effect size (d) = -2.87 [-3.88, -1.66]). Conclusion :Oral iron supplementation during 2–4 weeks of moderate altitude exposure may enhance Hbmass production and assist the maintenance of iron balance in some athletes with low pre-altitude iron stores

Recreational soccer as sport medicine for middle-aged and older adults: A systematic review

Background Strategies to prevent or attenuate the age-related decline in physical and physiological function and reduce chronic disease risk factors are of clinical importance. Objective To examine the health benefits of recreational soccer in middle-aged and older adults. Design Systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data sources All available records up until 9 June 2017 in PubMed, Web of Science, SPORTDiscus, MEDLINE, Embase, CINAHL Plus, PsycINFO and Cochrane Library databases. Eligibility criteria for selecting studies All randomised trials with or without a control group (randomised controlled trials or randomised uncontrolled trials) and non-randomised controlled trials that used recreational soccer, which includes small-sided soccer games, as the sole or principal intervention, and reported relevant effects in untrained/sedentary, healthy or unhealthy adults aged 40 years and above were included. Results Five trials described in 13 articles were included, which scored 6–9 out of 12 points on the modified Delphi quality rating scale. The duration was from 12 to 52 weeks, with various frequencies, volumes and game formats performed both outdoors and indoors with men and women. The trials indicate that recreational soccer may result in improvement in cardiovascular function, body composition and functional ability, although no significant changes were observed in postural balance. Conclusion Recreational soccer should be considered an alternative exercise modality for untrained, healthy or unhealthy middle-aged and older adults of both sexes to maintain an active lifestyle and mitigate a wide array of physical and physiological age-related changes

Mechanical suppression of osteolytic bone metastases in advanced breast cancer patients: A randomised controlled study protocol evaluating safety, feasibility and preliminary efficacy of exercise as a targeted medicine

Background: Skeletal metastases present a major challenge for clinicians, representing an advanced and typically incurable stage of cancer. Bone is also the most common location for metastatic breast carcinoma, with skeletal lesions identified in over 80% of patients with advanced breast cancer. Preclinical models have demonstrated the ability of mechanical stimulation to suppress tumour formation and promote skeletal preservation at bone sites with osteolytic lesions, generating modulatory interference of tumour-driven bone remodelling. Preclinical studies have also demonstrated anti-cancer effects through exercise by minimising tumour hypoxia, normalising tumour vasculature and increasing tumoural blood perfusion. This study proposes to explore the promising role of targeted exercise to suppress tumour growth while concomitantly delivering broader health benefits in patients with advanced breast cancer with osteolytic bone metastases. Methods: This single-blinded, two-armed, randomised and controlled pilot study aims to establish the safety, feasibility and efficacy of an individually tailored, modular multi-modal exercise programme incorporating spinal isometric training (targeted muscle contraction) in 40 women with advanced breast cancer and stable osteolytic spinal metastases. Participants will be randomly assigned to exercise or usual medical care. The intervention arm will receive a 3-month clinically supervised exercise programme, which if proven to be safe and efficacious will be offered to the control-arm patients following study completion. Primary endpoints (programme feasibility, safety, tolerance and adherence) and secondary endpoints (tumour morphology, serum tumour biomarkers, bone metabolism, inflammation, anthropometry, body composition, bone pain, physical function and patient-reported outcomes) will be measured at baseline and following the intervention. Discussion: Exercise medicine may positively alter tumour biology through numerous mechanical and nonmechanical mechanisms. This randomised controlled pilot trial will explore the preliminary effects of targeted exercise on tumour morphology and circulating metastatic tumour biomarkers using an osteolytic skeletal metastases model in patients with breast cancer. The study is principally aimed at establishing feasibility and safety. If proven to be safe and feasible, results from this study could have important implications for the delivery of this exercise programme to patients with advanced cancer and sclerotic skeletal metastases or with skeletal lesions present in haematological cancers (such as osteolytic lesions in multiple myeloma), for which future research is recommended. Trial registration: anzctr.org.au, ACTRN-12616001368426. Registered on 4 October 2016