Resistance Exercise and Skeletal Muscle-Related Outcomes in Patients with Cancer: A Systematic Review.

BACKGROUND: Skeletal muscle loss is prevalent throughout the cancer continuum and correlated with morbidity and mortality. Resistance exercise has been trialed to mitigate skeletal muscle loss. This systematic review summarizes and qualitatively synthesizes the effects of resistance exercise on muscle-related outcomes in adult cancer populations, including skeletal muscle mass, performance and muscle-related biomarkers. METHODS: The systematic review protocol was developed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). We searched electronic databases including AMED, CENTRAL, CINAHL, CIRRIE, EMBASE, MEDLINE, PEDro, REHABDATA, Scopus, and SPORTDiscus from inception to December 2021. We included randomized controlled trials that investigated the effects of resistance exercise on muscle-related outcomes in adult cancer populations. Interventions that involved any resistance exercise were included. Muscle-related outcomes were categorized as skeletal muscle mass (e.g., lean mass, appendicular muscle mass), muscle performance (e.g., muscle strength, physical function), and muscle-related biomarkers (e.g., muscle cells, metabolic/inflammatory markers). Risk of bias (RoB) was assessed using the Cochrane ROB tool. RESULTS: A total of 102 studies from 101 randomized controlled trials were included. The majority of studies focused on breast cancer (46%) and those who completed treatment (43%). Resistance exercise interventions were largely 3-4 months long (48%), combined with aerobic exercise (56%), at a vigorous intensity (25%), and in-person/supervised settings (57%). Among the studies assessing muscle mass, performance, and biomarkers ( n = 42, 83, and 22, respectively), resistance exercise interventions improved upper/lower body or appendicular muscle mass (67%-100%), muscle strength (61%-68%), and physical function (74%-100%). Most biomarkers did not show significant changes (75%-100%) or showed inconsistent results. CONCLUSIONS: Generally, resistance exercise had positive effects on skeletal muscle mass and performance with no negative effects compared to controls. Our findings demonstrated that resistance exercise may be an effective strategy to attenuate deterioration or exert improvements in muscle mass and performance outcomes.

Efficacy of resistive exercise on skeletal muscle-related outcomes in cancer survivors: a systematic review protocol.

BACKGROUND: Symptom burden and adverse treatment effects can negatively impact physical function, health-related outcomes, and quality of life in cancer survivors. Resistive exercise that improves skeletal muscle function can ameliorate these complications, but the central role of the skeletal muscle in mediating improvements in patient-related outcomes has not been explored. This protocol describes the rationale and methods for a systematic review that aims to determine the effects of resistive exercise on the skeletal muscle hypertrophy, muscle performance, and muscle-related biomarkers in cancer survivors. METHODS: A systematic review will be conducted on peer-reviewed randomized controlled trials (RCTs) that employ resistive exercise interventions for cancer survivors. The following electronic databases will be searched: AMED, CENTRAL, CINAHL, CIRRIE, EMBASE, MEDLINE, PEDro, REHABDATA, Scopus, and SPORTDiscus. Studies will be considered for inclusion if they present quantitative data in adult cancer survivors on skeletal muscle characteristics (e.g., muscle mass), muscle performance (e.g., strength), or skeletal muscle-related biomarkers (e.g., myocellular satellite cells). Secondary outcomes will be physical function (e.g., stair climb) and patient-reported outcomes (e.g., fatigue). Data will be reported through a narrative that describes study design, participants, interventions, and outcome characteristics. DISCUSSION: This systematic review will help clarify the influence of resistive exercise on factors relating to the skeletal muscle in adult cancer survivors. Findings may provide insight into optimal exercise selection for evidence-based practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: #277791 [under review].

Effect of Periodized Resistance Training on Skeletal Muscle During Androgen Deprivation Therapy for Prostate Cancer: A Pilot Randomized Trial.

PURPOSE: Prostate cancer survivors (PCS) receive androgen deprivation therapy (ADT) as treatment for recurrent cancer, yet ADT is associated with loss of skeletal muscle and physical function. Resistance training can counter both muscle and physical function loss; however, an understanding of the molecular responses of skeletal muscle to resistance training during ADT is still undefined. This sub-analysis of the original randomized, controlled pilot trial investigated effects of 12 weeks of periodized resistance training on mRNA expression of the anabolic genes IGF-1, myogenin, PGC-1α4 and the catabolic genes myostatin and MuRF-1 in skeletal muscle of PCS on ADT. Secondary aims investigated if changes in lean mass and physical function correlated with changes in mRNA expression. METHODS: PCS on ADT (n = 17) were randomized to 12 weeks of supervised resistance training (EXE, n = 9) or home-based stretching (STRETCH, n = 8) 3 days per week. Outcomes were assessed at baseline and post-intervention. Muscle biopsies were analyzed by RT-PCR for mRNA expression. Body composition was assessed through dual-energy X-ray absorptiometry, and physical function through muscular strength, timed up and go, stair climb, and 400 m walk. RESULTS: MuRF-1 mRNA expression was significantly greater in EXE compared to STRETCH post-intervention (P = .005). Change in MuRF-1 mRNA expression significantly correlated with improvements in strength and physical function (P < .05), while change in IGF-1 expression correlated with change in lean mass (P = .015). CONCLUSION: Twelve weeks of resistance training increased mRNA expression of MuRF-1 in skeletal muscle of PCS on ADT. Elevations in resting mRNA expression of IGF-1, myogenin and PGC-1α4, and reduction in mRNA expression of myostatin that are typically expected following resistance training were not observed.

Impact of resistance training on body composition and metabolic syndrome variables during androgen deprivation therapy for prostate cancer: a pilot randomized controlled trial.

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.