Dennis R Taaffe1,2,3, Laurien M Buffart1,4, Robert U Newton1,2,5,6, Nigel Spry1,7,8, James Denham9,10, David Joseph1,8,11, David Lamb12, Suzanne K Chambers1,13,14,15, Daniel A Galvão1,2. 1. Exercise Medicine Research Institute, Edith Cowan University, Joondalup, WA, Australia. 2. School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia. 3. School of Human Movement and Nutrition Sciences, University of Queensland, Brisbane, Qld, Australia. 4. Departments of Epidemiology and Biostatistics and Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands. 5. Institute of Human Performance, University of Hong Kong, Hong Kong, Hong Kong. 6. University of Queensland Centre for Clinical Research, University of Queensland, Brisbane, Qld, Australia. 7. Genesis CancerCare, Joondalup, WA, Australia. 8. Faculty of Medicine, University of Western Australia, Nedlands, WA, Australia. 9. School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia. 10. Newcastle Mater Hospital, Newcastle, NSW, Australia. 11. Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia. 12. University of Otago, Wellington, New Zealand. 13. Menzies Health Institute Queensland, Griffith University, Gold Coast, Qld, Australia. 14. Centre for Research in Cancer, Cancer Council Queensland, Brisbane, Qld, Australia. 15. Prostate Cancer Foundation of Australia, Sydney, NSW, Australia.
Abstract
OBJECTIVES: To explore if duration of previous exposure to androgen deprivation therapy (ADT) in men with prostate cancer (PCa) undertaking a year-long exercise programme moderates the exercise response with regard to body composition and muscle performance, and also to explore the moderator effects of baseline testosterone, time since ADT, and baseline value of the outcome. PATIENTS AND METHODS: In a multicentre randomized controlled trial, 100 men who had previously undergone either 6 months (short-term) or 18 months (long-term) of ADT in combination with radiotherapy, as part of the TROG 03.04 RADAR trial, were randomized to 6 months supervised exercise, followed by a 6-month home-based maintenance programme, or to printed physical activity educational materialfor 12 months across 13 university-affiliated exercise clinics in Australia and New Zealand. The participants were long-term survivors of PCa with a mean age of 71.7 ± 6.4 years, and were assessed for lower extremity performance (repeated chair rise), with a subset of men (n = 57) undergoing additional measures for upper and lower body muscle strength and body composition (lean mass, fat mass, appendicular skeletal muscle [ASM]) by dual X-ray absorptiometry. Data were analysed using generalized estimating equations. RESULTS: Time on ADT significantly moderated the exercise effects on chair rise (βinteraction = -1.3 s, 95% confidence interval [CI] -2.6 to 0.0), whole-body lean mass (βinteraction = 1194 g, 95% CI 234 to 2153) and ASM mass (βinteraction = 562 g, 95% CI 49 to 1075), and approached significance for fat mass (βinteraction = -1107 g, 95% CI -2346 to 132), with greater benefits for men previously on long-term ADT. At 6 months, the intervention effects on chair rise time -1.5 s (95% CI -2.5 to -0.5), whole-body lean mass 824 g (95% CI 8 to 1640), ASM mass 709 g (95% CI 260 to 1158), and fat mass -1377 g (95% CI -2156 to -598) were significant for men previously on long-term ADT, but not for men on short-term ADT. At 12 months, the intervention effects for men on long-term ADT remained significant for the chair rise, with improved performance (-2.0 s, 95% CI -3.0 to -1.0) and increased ASM (537 g, 95% CI 153 to 921). Time on ADT did not moderate the exercise effects on muscle strength, nor did time since ADT cessation moderate any intervention effects. Similarly, testosterone and baseline values of the outcome had negligible moderator effects. CONCLUSIONS:Men with PCa previously treated long-term withADT respond more favourably to exercise in terms of lower body muscle performance and body composition (lean and fat mass, and ASM) than those with short-term ADT exposure. As a result, men who were formerly on long-term androgen suppression regimens should be especially prescribed exercise medicine interventions to alleviate residual treatment-related adverse effects.
RCT Entities:
OBJECTIVES: To explore if duration of previous exposure to androgen deprivation therapy (ADT) in men with prostate cancer (PCa) undertaking a year-long exercise programme moderates the exercise response with regard to body composition and muscle performance, and also to explore the moderator effects of baseline testosterone, time since ADT, and baseline value of the outcome. PATIENTS AND METHODS: In a multicentre randomized controlled trial, 100 men who had previously undergone either 6 months (short-term) or 18 months (long-term) of ADT in combination with radiotherapy, as part of the TROG 03.04 RADAR trial, were randomized to 6 months supervised exercise, followed by a 6-month home-based maintenance programme, or to printed physical activity educational material for 12 months across 13 university-affiliated exercise clinics in Australia and New Zealand. The participants were long-term survivors of PCa with a mean age of 71.7 ± 6.4 years, and were assessed for lower extremity performance (repeated chair rise), with a subset of men (n = 57) undergoing additional measures for upper and lower body muscle strength and body composition (lean mass, fat mass, appendicular skeletal muscle [ASM]) by dual X-ray absorptiometry. Data were analysed using generalized estimating equations. RESULTS: Time on ADT significantly moderated the exercise effects on chair rise (βinteraction = -1.3 s, 95% confidence interval [CI] -2.6 to 0.0), whole-body lean mass (βinteraction = 1194 g, 95% CI 234 to 2153) and ASM mass (βinteraction = 562 g, 95% CI 49 to 1075), and approached significance for fat mass (βinteraction = -1107 g, 95% CI -2346 to 132), with greater benefits for men previously on long-term ADT. At 6 months, the intervention effects on chair rise time -1.5 s (95% CI -2.5 to -0.5), whole-body lean mass 824 g (95% CI 8 to 1640), ASM mass 709 g (95% CI 260 to 1158), and fat mass -1377 g (95% CI -2156 to -598) were significant for men previously on long-term ADT, but not for men on short-term ADT. At 12 months, the intervention effects for men on long-term ADT remained significant for the chair rise, with improved performance (-2.0 s, 95% CI -3.0 to -1.0) and increased ASM (537 g, 95% CI 153 to 921). Time on ADT did not moderate the exercise effects on muscle strength, nor did time since ADT cessation moderate any intervention effects. Similarly, testosterone and baseline values of the outcome had negligible moderator effects. CONCLUSIONS:Men with PCa previously treated long-term with ADT respond more favourably to exercise in terms of lower body muscle performance and body composition (lean and fat mass, and ASM) than those with short-term ADT exposure. As a result, men who were formerly on long-term androgen suppression regimens should be especially prescribed exercise medicine interventions to alleviate residual treatment-related adverse effects.
Authors: Pedro Lopez; Dennis R Taaffe; Robert U Newton; Laurien M Buffart; Daniel A Galvão Journal: Prostate Cancer Prostatic Dis Date: 2020-11-20 Impact factor: 5.554