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Resistance training reduces disability in prostate cancer survivors on androgen deprivation therapy: evidence from a randomized controlled trial.

ABSTRACT: To investigate whether functionally based resistance exercise could improve strength, physical function, and disability among prostate cancer survivors (PCS) on androgen deprivation therapy (ADT); and to explore potential mediators of changes in outcomes from exercise.Randomized controlled trial.Academic medical center.PCS (N=51; mean age, 70.2y) on ADT.PCS were randomized to moderate to vigorous intensity resistance training or stretching (placebo control) for 1 year.Maximal leg press and bench press strength, objective and self-reported physical function, and self-reported disability. Hierarchical linear modeling was used to test for significant group × time differences adjusting for covariates.Retention in the study was 84%, and median attendance to supervised classes was 84% in the resistance group. No study-related injuries occurred. Maximal leg strength (P=.032) and bench press strength (P=.027) were improved after 1 year of resistance training, whereas little change occurred from stretching. Self-reported physical function improved with resistance training, whereas decreases occurred from stretching (P=.016). Disability lessened more with resistance training than stretching (P=.018). One-year change in leg press strength mediated the relation between groups (resistance or stretching) and 1-year change in self-reported disability (P<.05).One year of resistance training improved muscle strength in androgen-deprived PCS. Strengthening muscles using functional movement patterns may be an important feature of exercise programs designed to improve perceptions of physical function and disability. Findings from this study contribute to the mounting evidence that exercise should become a routine part of clinical care in older men with advanced prostate cancer.

SUBMITTER: Winters-Stone KM

PROVIDER: S-EPMC4433162 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Resistance training reduces disability in prostate cancer survivors on androgen deprivation therapy: evidence from a randomized controlled trial.

Winters-Stone Kerri M KM Dobek Jessica C JC Bennett Jill A JA Dieckmann Nathan F NF Maddalozzo Gianni F GF Ryan Christopher W CW Beer Tomasz M TM

Archives of physical medicine and rehabilitation 20140903 1

<h4>Objectives</h4>To investigate whether functionally based resistance exercise could improve strength, physical function, and disability among prostate cancer survivors (PCS) on androgen deprivation therapy (ADT); and to explore potential mediators of changes in outcomes from exercise.<h4>Design</h4>Randomized controlled trial.<h4>Setting</h4>Academic medical center.<h4>Participants</h4>PCS (N=51; mean age, 70.2y) on ADT.<h4>Intervention</h4>PCS were randomized to moderate to vigorous intensit ...[more]

PMID: 25194450

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Project description:INTRODUCTION:Prostate cancer survivors (PCS) receiving androgen deprivation therapy (ADT) experience deleterious side effects such as unfavourable changes in cardiometabolic factors that lead to sarcopenic obesity and metabolic syndrome (MetS). While loss of lean body mass (LBM) compromises muscular strength and quality of life, MetS increases the risk of cardiovascular disease and may influence cancer recurrence. Exercise can improve LBM and strength, and may serve as an alternative to the pharmacological management of MetS in PCS on ADT. Prior exercise interventions in PCS on ADT have been effective at enhancing strength, but only marginally effective at enhancing body composition and ameliorating cardiometabolic risk factors. This pilot trial aims to improve on existing interventions by employing periodised resistance training (RT) to counter sarcopenic obesity in PCS on ADT. Secondary aims compare intervention effects on cardiometabolic, physical function, quality of life and molecular skeletal muscle changes. An exploratory aim examines if protein supplementation (PS) in combination with RT elicits greater changes in these outcomes. METHODS AND ANALYSIS:A 2×2?experimental design is used in 32 PCS on ADT across a 12-week intervention period. Participants are randomised to resistance training and protein supplementation (RTPS), RT, PS or control. RT and RTPS groups perform supervised RT three times per week for 12 weeks, while PS and RTPS groups receive 50 g whey protein per day. This pilot intervention applies a multilayered approach to ameliorate detrimental cardiometabolic effects of ADT while investigating molecular mechanisms underlying skeletal muscle changes in PCS. ETHICS AND DISSEMINATION:This trial was approved by the University of Southern California Institutional Review Board (HS-13-00315). Results from this trial will be communicated in peer-reviewed publications and scientific presentations. TRIAL REGISTRATION NUMBER:NCT01909440; Pre-results.

Project description:IntroductionAndrogen deprivation therapy (ADT) has detrimental effects on body composition, metabolic health, physical functioning, bone mineral density (BMD) and health-related quality of life (HRQOL) in men with prostate cancer. We investigated whether a 12-month home-based progressive resistance training (PRT) programme, instituted at the start of ADT, could prevent these adverse effects.MethodsTwenty-five patients scheduled to receive at least 12 months of ADT were randomly assigned to either usual care (UC) (n = 12) or PRT (n = 13) starting immediately after their first ADT injection. Body composition, body cell mass (BCM; a functional component of lean body mass), BMD, physical function, insulin sensitivity and HRQOL were measured at 6 weeks and 6 and 12 months. Data were analysed by a linear mixed model.ResultsADT had a negative impact on body composition, BMD, physical function, glucose metabolism and HRQOL. At 12 months, the PRT group had greater reductions in BCM by - 1.9 ± 0.8 % (p = 0.02) and higher gains in fat mass by 3.1 ± 1.0 % (p = 0.002), compared to the UC group. HRQOL domains were maintained or improved in the PRT versus UC group at 6 weeks (general health, p = 0.04), 6 months (vitality, p = 0.02; social functioning, p = 0.03) and 12 months (mental health, p = 0.01; vitality, p = 0.02). A significant increase in the Matsuda Index in the PRT versus UC group was noted at 6 weeks (p = 0.009) but this difference was not maintained at subsequent timepoints. Between-group differences favouring the PRT group were also noted for physical activity levels (step count) (p = 0.02). No differences in measures of BMD or physical function were detected at any time point.ConclusionA home-based PRT programme instituted at the start of ADT may counteract detrimental changes in body composition, improve physical activity and mental health over 12 months.Trial registrationAustralian and New Zealand Clinical Trials Registry, ACTRN12616001311448.

Project description:BACKGROUND:Prostate cancer patients on androgen deprivation therapy (ADT) experience adverse effects such as lean mass loss, known as sarcopenia, fat gain, and changes in cardiometabolic factors that increase risk of metabolic syndrome (MetS). Resistance training can increase lean mass, reduce body fat, and improve physical function and quality of life, but no exercise interventions in prostate cancer patients on ADT have concomitantly improved body composition and MetS. This pilot trial investigated 12 weeks of resistance training on body composition and MetS changes in prostate cancer patients on ADT. An exploratory aim examined if a combined approach of training and protein supplementation would elicit greater changes in body composition. METHODS:Prostate cancer patients on ADT were randomized to resistance training and protein supplementation (TRAINPRO), resistance training (TRAIN), protein supplementation (PRO), or control stretching (STRETCH). Exercise groups (EXE?=?TRAINPRO, TRAIN) performed supervised exercise 3 days per week for 12 weeks, while non-exercise groups (NoEXE?=?PRO, STRETCH) performed a home-based stretching program. TRAINPRO and PRO received 50 g?day-?1 of whey protein. The primary outcome was change in lean mass assessed through dual energy x-ray absorptiometry. Secondary outcomes examined changes in sarcopenia, assessed through appendicular skeletal mass (ASM) index (kg/m2), body fat %, strength, physical function, quality of life, MetS score and the MetS components of waist circumference, blood pressure, glucose, high-density lipoprotein-cholesterol, and triglyceride levels. RESULTS:A total of 37 participants were randomized; 32 participated in the intervention (EXE n?=?13; NoEXE n?=?19). At baseline, 43.8% of participants were sarcopenic and 40.6% met the criteria for MetS. Post-intervention, EXE significantly improved lean mass (d?=?0.9), sarcopenia prevalence (d?=?0.8), body fat % (d?=?1.1), strength (d?=?0.8-3.0), and prostate cancer-specific quality of life (d?=?0.9) compared to NoEXE (p?<?0.05). No significant differences were observed between groups for physical function or MetS-related variables except waist circumference (d?=?0.8). CONCLUSIONS:A 12-week resistance training intervention effectively improved sarcopenia, body fat %, strength and quality of life in hypogonadal prostate cancer patients, but did not change MetS or physical function. PRO did not offer additional benefit in improving body composition. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01909440 . Registered 24 July 2013.

Project description:BACKGROUND:Prostate cancer (PCa), the second most common cancer affecting men worldwide, shows a broad spectrum of biological and clinical behaviour representing the epiphenomenon of an extreme heterogeneity. Androgen deprivation therapy is the mainstay of treatment for advanced forms but after few years the majority of patients progress to castration-resistant prostate cancer (CRPC), a lethal form that poses considerable therapeutic challenges. METHODS:Western blotting, immunocytochemistry, invasion and reporter assays, and in vivo studies were performed to characterize androgen resistant sublines phenotype in comparison to the parental cell line LNCaP. RNA microarray, mass spectrometry, integrative transcriptomic and proteomic differential analysis coupled with GeneOntology and multivariate analyses were applied to identify deregulated genes and proteins involved in CRPC evolution. RESULTS:Treating the androgen-responsive LNCaP cell line for over a year with 10 ?M bicalutamide both in the presence and absence of 0.1 nM 5-?-dihydrotestosterone (DHT) we obtained two cell sublines, designated PDB and MDB respectively, presenting several analogies with CRPC. Molecular and functional analyses of PDB and MDB, compared to the parental cell line, showed that both resistant cell lines were PSA low/negative with comparable levels of nuclear androgen receptor devoid of activity due to altered phosphorylation; cell growth and survival were dependent on AKT and p38MAPK activation and PARP-1 overexpression; their malignant phenotype increased both in vitro and in vivo. Performing bioinformatic analyses we highlighted biological processes related to environmental and stress adaptation supporting cell survival and growth. We identified 15 proteins that could direct androgen-resistance acquisition. Eleven out of these 15 proteins were closely related to biological processes involved in PCa progression. CONCLUSIONS:Our models suggest that environmental factors and epigenetic modulation can activate processes of phenotypic adaptation driving drug-resistance. The identified key proteins of these adaptive phenotypes could be eligible targets for innovative therapies as well as molecules of prognostic and predictive value.

Project description:Metastatic and castration-resistant disease is a fatal manifestation of prostate cancer (PCa). The mechanism through which resistance to androgen deprivation in PCa is developed remains largely unknown. Our understanding of the tumor microenvironment (TME) and key signaling pathways between tumors and their TME is currently changing in light of the generation of new knowledge with regard to cancer progression. A disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) is a membranous bridge forming cell-cell and cell-matrix connections that regulate tumor aggressiveness and metastasis. However, it is not known whether ADAM9 expressed in the TME contributes to the CRPC phenotype. In this study, we aimed to investigate the expression patterns of ADAM9 in prostate cancer-associated fibroblasts (CAFs). We also intended to elucidate the effects of both stromal cell- and cancer cell-derived ADAM9 on the progression of CRPC and the implicated molecular pathways. By using both clinical specimens and cell lines, we herein showed that unlike the membrane anchored ADAM9 overexpressed by both PCa cells and prostate CAFs, the secreted isoform of ADAM9 (sADAM9) was strongly detected in CAFs, but rarely in tumor cells, and that could be a serum marker for PCa patients. We demonstrated that functionally sADAM9 are characterized as chemoattractant for the directed movement of androgen-independent PCa cells through integrin downstream FAK/AKT pathway, supporting that elevated sADAM9 by prostate CAFs could be responsible for the promotion of CRPC metastasis. Moreover, by stimulating PCa cells with sADAM9, we found that ubinuclein-2 (UBN2) expression was increased. A positive correlation of ADAM9 and UBN2 expression was observed in androgen receptor-expressing PCa cell lines and further confirmed in clinical PCa specimens. Using a genetic modification approach, we identified UBN2 as a downstream target gene of ADAM9 that is critical for the survival of androgen-dependent PCa cells in response to androgen deprivation, through the induction and effect of the aldo-keto reductase family 1 member C3 (AKR1C3). Collectively, our results reveal a novel action of ADAM9 on the transition of androgen-dependent PCa cells into an androgen-independent manner through the UBN2/AKR1C3 axis; the aforementioned action could contribute to the clinically-observed acquired androgen-deprivation therapy resistance.

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Resistance training reduces disability in prostate cancer survivors on androgen deprivation therapy: evidence from a randomized controlled trial.

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Resistance training reduces disability in prostate cancer survivors on androgen deprivation therapy: evidence from a randomized controlled trial.

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