Effects of exercise on Sexual function and CArdiovascular health in men with prostate cancer (ESCA) Study

INTERVENTION: This study involves two components. The first, an interventional study which will compare the effects of a 12‐week exercise intervention to usual care in men who have, or who have previously had, prostate cancer. The second, a situational appraisal of this exercise intervention. 1. Exercise Intervention The intervention will be a structured and individualised 12‐week exercise program with the following components: 1) Participants will aim to complete 36 one‐hour exercise sessions during this 12‐week period (equating to three exercise sessions per week) in either a supervised gymnasium or in the participant’s community/home (if deemed the participant is able to safely and effectively complete their exercises unsupervised). If participants are unable to reach the target 36 sessions during these 12 weeks (i.e. they miss sessions due to excess treatment‐related side effects), then they will be provided with the option of performing make‐up sessions during this 12‐week period (i.e. a participant may complete two sessions one week, then four sessions the following week). Alternatively, participants will be provided with the option of completing as many of the remaining sessions as possible during one additional week, making the intervention 13 weeks in duration (at most) for these participants. 2) Supervised exercise sessions will either be individual or group‐based and be supervised by an accredited exercise physiologist (AEP). Unsupervised home‐based exercise sessions will be individual. 3) The exercise intervention will taper from fully supervised (weeks 1‐4) to partially supervised with self‐managed sessions (weeks 5‐12). 4) Each session will include a tailored exercise program, including a combination of high intensity aerobic and resistance exercises. These tailored exercise programs will be reviewed after each exercise session and will take into account each participant’s disease‐status, exercise performance and exercise preferences. High‐int CONDITION: Cancer ‐ Prostate Cardiovascular ‐ Other cardiovascular diseases Prostate Cancer;Sexual Function;Cardiovascular Disease Risk; ; Prostate Cancer ; Sexual Function ; Cardiovascular Disease Risk Reproductive Health and Childbirth ‐ Other reproductive health and childbirth disorders PRIMARY OUTCOME: Changes in erectile function and intercourse satisfaction (composite outcome), as assessed via the Abridged version of the International Index of Erectile Function (IIEF‐5) questionnaire [Baseline and 12 weeks (primary timepoint) after randomisation] SECONDARY OUTCOME: Adverse Events (AE) occurrence during the intervention period, as assessed via weekly face‐to‐face contact (at exercise sessions) from baseline to week 12. AE which might be directly related to the intervention (to be determined by an accredited exercise physiologist) will be assessed using the US Department of Health and Human Services Common Terminology Criteria for Adverse Events (CTCAE). Possible AE include: ; ‐ Cardiac events (e.g. Myocardial Infarction, Stroke, Cardiac Arrhythmia) ; ‐ Musculoskeletal events (e.g. Development of Lower Back Pain, Knee Pain) ; ‐ Treatment‐related events (e.g. Fatigue development, Immunocompromised i.e. flu) ; ‐ Weight ; ‐ Height ; ‐ Body mass index (BMI) ; ‐ Waist and hip circumferences ; ‐ Interleukin 1 beta (IL‐1beta) ; ‐ Interleukin 6 (IL‐6) ; ‐ Interleukin 2 (IL‐2) ; ‐ Tumor Necrosis Factor alpha (TNFalpha) ; ‐ Cardiac Troponin‐I ; ‐ pro‐Brain Natriuretic Peptide (pro‐BNP) ; ‐ High‐sensitivity C‐reactive Protein (hs‐CRP) ; ‐ Low‐density lipoprotein (LDL) ; ‐ High‐density lipoprotein (HDL) ; ‐ Total cholesterol (TC) ; ‐ Triglycerides (TG) ; ‐ Fasting glucose ; ‐ Haemoglobin A1c (HbA1c) ; ‐ Concurrent prostate cancer treatment‐related events (e.g. Pain, Skin irritation)[Every supervised exercise session from baseline to week 12, throughout the 12‐week exercise intervention period ] Changes in a hormonal blood marker, as assessed via levels of testosterone. ; All bloods for Secondary Outcomes numbered 10‐15 collected via 10mL and 6mL serum tubes, a 10mL Ethylenediaminetetraacetic acid (EDTA) tube, a 4mL Lith/Hep tube, and a 2mL glucose tube (32mL in total)[Baseline and 12 weeks after randomisation] Changes in autonomic nervous system function, as assessed via heart rate and blood pressure responses to both deep breathing and a Valsalva Manoeuvre using a Finapres NOVA System[Baseline and 12 weeks after randomisation] Changes in autonomic nervous system function, as assessed via Heart Rate Variability (HRV) using a resting 3‐lead electrocardiogram[Baseline and 12 weeks after randomisation] Changes in body composition, as assessed via muscle cross sectional area and bone density of the tibia and femur using peripheral Quantitative Computed Tomography (pQCT)[Baseline and 12 weeks after randomisation] Changes in body composition, as assessed via whole‐body bone, muscle and fat mass using Dual Energy X‐ray Absorptiometry (DEXA)[Baseline and 12 weeks after randomisation] Changes in body composition, as assessed via: ; ‐ Waist‐to‐hip ratio (WHR)[Baseline and 12 weeks after randomisation] Changes in Brain Blood Flow and Carotid Dilation, as assessed via carotid‐artery flow‐mediated dilation and neurovascular coupling using a doppler ultrasound and a Finapres NOVA System ; [Baseline and 12 weeks after randomisation] Changes in cardiorespiratory fitness (VO2Peak), as assessed via a Cardiopulmonary Exercise Test (CPET) using a cycle ergometer and metabolic system[Baseline and 12 weeks after randomisation] Changes in central blood pressures and pulse wave characteristics, as assessed via Pulse Wave Analysis (PWA) using a SphygmoCor XCEL PWA and PWV system[Baseline and 12 weeks after randomisation] Changes in central pulse transfer times, as assessed via Pulse Wave Velocity (PWV) using a SphygmoCor XCEL PWA and PWV system[Baseline and 12 weeks after randomisation] Changes in cytokine blood markers as assessed via; ; All bloods for Secondary Outcomes numbered 10‐15 collected via 10mL and 6mL serum tubes, a 10mL Ethylenediaminetetraacetic acid (EDTA) tube, a 4mL Lith/Hep tube, and a 2mL glucose tube (32mL in total)[Baseline and 12 weeks after randomisation] Changes in macro vascular function, as assessed via Brachial‐Artery Flow‐mediated Dilation (BA‐FMD) using doppler ultrasound ; [Baseline and 12 weeks after randomisation] Changes in macro vascular function, as assessed via Carotid Distensibility (CD) using a doppler ultrasound, a hand‐held PowerLab tonometer connected to LabChart, and a Finapres NOVA System[Baseline and 12 weeks after randomisation] Changes in macro vascular structure, as assessed via Carotid Intima‐media Thickness (CIMT) using doppler ultrasound[Baseline and 12 weeks after randomisation] Changes in metabolic and hormonal blood markers as assessed via; ; ‐ Insulin ; ‐ Insulin‐like growth factor 1 (IGF‐1) ; All bloods for Secondary Outcomes numbered 10‐15 collected via 10mL and 6mL serum tubes, a 10mL Ethylenediaminetetraacetic acid (EDTA) tube, a 4mL Lith/Hep tube, and a 2mL glucose tube (32mL in total)[Baseline and 12 weeks after randomisation] Changes in oxidative stress as assessed via plasma nitrate and nitrite levels. INCLUSION CRITERIA: ‐ Men with a histologically‐confirmed diagnosis of prostate cancer ‐ Undergoing watchful waiting, active surveillance, or previous or concurrent treatment with any anti‐cancer treatment/s ‐ Aged >18 years ‐ >4 weeks since major surgery ‐ No co‐morbid condition or falls risk that could prevent safe completion of the intervention ; All bloods for Secondary Outcomes numbered 10‐15 collected via 10mL and 6mL serum tubes, a 10mL Ethylenediaminetetraacetic acid (EDTA) tube, a 4mL Lith/Hep tube, and a 2mL glucose tube (32mL in total)[Baseline and 12 weeks after randomisation] Changes in erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall sexual satisfaction (composite outcome), as assessed via the International Index of Erectile Function (IIEF) questionnaire [Baseline and 12 weeks after randomisation] Changes in fatigue, as assessed via the Functional Assessment of Chronic Illness Therapy‐Fatigue (FACIT‐Fatigue) Subscale questionnaire [Baseline and 12 weeks after randomisation] Changes in habitual dietary intake, as assessed via a three‐day diet diary[Baseline and 12 weeks after randomisation] Changes in habitual physical activity and sedentary behaviours, as assessed via accelerometery using a ActiGraph GT3X+ accelerometer[Baseline and 12 weeks after randomisation] Changes in inflammatory blood markers, as assessed via levels of: ; All bloods for Secondary Outcomes numbered 10‐15 collected via 10mL and 6mL serum tubes, a 10mL Ethylenediaminetetraacetic acid (EDTA) tube, a 4mL Lith/Hep tube, and a 2mL glucose tube (32mL in total) ; [Baseline and 12 weeks after randomisation] Changes in participant's perceived performance status, as assessed via the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale[Baseline and 12 weeks after randomisation] Changes in prostate cancer cell growth, as assessed via cell culture analyses (using cell number assays and cell death assays). ; All bloods for Secondary Outcomes numbered 10‐15 collected via 10mL and 6mL serum tubes, a 10mL Ethylenediaminetetraacetic acid (EDTA) tube, a 4mL Lith/Hep tube, and a 2mL glucose tube (32mL in total)[Baseline and 12 weeks after randomisation] Changes in state and trait anxiety, as assessed via the Hospital Anxiety and Depression Scale (HADS) questionnaire[Baseline and 12 weeks after randomisation] Evaluation of factors relating to participant adherence to the exercise intervention, as assessed via a Cancer Exercise Adherence Survey specially designed for this study[Baseline (Intervention group ONLY)] Resource utilisation in both groups during the intervention period, as assessed via discussion in the situational appraisal component of the study. Discussion of labour (e.g. to deliver the intervention) and non‐labour (e.g. gymnasium use, pain medication) costs. Resource use will be costed at market rates (e.g. industrial award rates for labour costs), for use in cost‐effectiveness analyses.[Following exercise intervention completion] ‐ Sexual dysfunction score of moderate (score = 8‐11/25), mild‐to‐moderate (score = 12‐16/25), or mild (score = 17‐21/25), as assessed by the abridged version of the International Index of Erectile Function (IIEF‐5) ‐ Cognitively capable of consent