Time on androgen deprivation therapy and adaptations to exercise: secondary analysis from a 12-month randomized controlled trial in men with prostate cancer

Objectives To explore if duration of prior exposure to androgen deprivation therapy (ADT) in men with prostate cancer (PCa) undertaking a yearlong exercise program moderates the exercise response on body composition and muscle performance. In addition, we explored the moderator effect of baseline testosterone, time since ADT, and baseline value of the outcome. Patients and Methods In a multicenter randomized controlled trial, 100 patients previously treated for either 6 months (short-term) or 18 months (long-term) 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 program, or to printed physical activity educational material for 12 months across 13 university-affiliated exercise clinics in Australia and New Zealand. Patients were long-term PCa survivors with a mean age of 71.7 ± 6.4 years, and were assessed for lower extremity performance (repeated chair rise) with a subset (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 (GEE). Results Time on ADT significantly moderated the exercise effects on chair rise (βinteraction= -1.3s, 95% CI= -2.6; 0.0), whole body lean (βinteraction= 1194g, 95% CI= 234; 2153) and ASM (βinteraction= 562g, 95% CI= 49; 1075) mass, and approached significance for fat mass (βinteraction= -1107g, 95% CI= -2346; 132), with larger 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 824 g (95% CI 8 to 1640), ASM 709 g (95% CI 260 to 1158), and fat -1377 g (95% CI -2156 to -598) mass were significant for men previously on long-term ADT, but not for men on short-term ADT. At 12 months, 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 PCa patients 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. This article is protected by copyright. All rights reserved.