What is the minimal dose for resistance exercise effectiveness in prostate cancer patients? Systematic review and meta-analysis on patient-reported outcomes

© 2020, The Author(s). Background: Active treatments for prostate cancer are well known to result in several adverse effects such as fatigue, depression and anxiety symptoms, impacting the overall quality of life (QoL) and wellbeing of a considerable proportion of patients. Resistance-based exercise interventions have shown positive effects to reduce or mitigate these treatment-related side effects. However, the minimal dosage required to derive these benefits is unknown. We systematically reviewed the resistance training effects in prostate cancer patients to determine the minimal dosage regarding the exercise components (mode, duration, volume and intensity) on fatigue, QoL, depression and anxiety. Methods: Using PRISMA guidelines, MEDLINE, CINAHL, EMBASE, SPORTDiscus and Web of Science databases were searched. Eligible randomised controlled trials examined prostate cancer patients undertaking resistance-based exercise programs during or following treatment. Meta-analysis was undertaken when more than three studies were included. Associations between resistance exercise components and its effects were tested by meta-regression analysis. Results: Eighteen trials involving 1112 men with prostate cancer were included. Resistance-based exercise programs resulted in significant effects on fatigue (effect size = −0.3, 95% CI: −0.4 to −0.2, P \u3c 0.001) and QoL (effect size = 0.2, 95% CI: 0.0 to 0.4, P = 0.018), with significant effects in specific questionnaires and domains of these outcomes. Resistance-based exercise effects on depression (effect size = −0.3, 95% CI: −0.7 to 0.0) and anxiety symptoms (effect size = −0.3, 95% CI: −0.5 to 0.0) were positive but not significant (P = 0.071 to 0.077). Meta-regression indicated no significant association between resistance exercise components with fatigue and QoL outcomes (P = 0.186–0.689). Conclusions: Low volume resistance exercise undertaken at a moderate-to-high intensity is sufficient to achieve significant fatigue and QoL benefits for men with prostate cancer and also mitigate depression and anxiety symptoms. A lower resistance exercise dosage than usually prescribed may help enhance adherence by reducing exercise barriers

Effects and moderators of exercise medicine on cardiometabolic outcomes in men with prostate cancer previously or currently undergoing androgen deprivation therapy: An individual patient data meta-analysis

Purpose: To examine the effects and moderators of exercise effects on cardiometabolic outcomes in men with prostate cancer previously or currently undergoing androgen deprivation therapy (ADT). Results: Seven trials including 560 patients were examined. Exercise resulted in significant effects on whole-body and regional fat mass (P ≤ 0.001). For whole-body fat mass, significant exercise effects were observed in patients who were unmarried (−1.4 kg, P \u3c 0.05) and who presented with higher fat mass levels (−1.0 kg, P \u3c 0.05). For diastolic blood pressure and low-density lipoprotein (LDL), younger (−4.7 mmHg, P \u3c 0.05) and older patients (−0.2 mmol.l-1, P \u3c 0.10) achieved greater effects, respectively. Regarding high-density lipoprotein (HDL), patients undertaking ADT + prostatectomy + radiotherapy derived significant exercise effects (0.3 mmol.l-1, P \u3c 0.05). Conclusions: Exercise effectively reduces fat mass across subgroups of men undergoing or following ADT with different characteristics. For diastolic blood pressure, HDL and LDL, groups based on age and treatment history could be specifically targeted with exercise medicine

Exploring moderators of the effect of high vs. low-to-moderate Intensity exercise on cardiorespiratory fitness during breast cancer treatment – Analyses of a subsample from the phys-can RCT

Introduction The results from the physical training and cancer randomized controlled trial (Phys-Can RCT) indicate that high intensity (HI) strength and endurance training during (neo-)adjuvant cancer treatment is more beneficial for cardiorespiratory fitness (CRF, measured as peak oxygen uptake [VO2peak]) than low-to-moderate intensity (LMI) exercise. Adherence to the exercise intervention and demographic or clinical characteristics of patients with breast cancer undergoing adjuvant treatment may moderate the exercise intervention effect on VO2peak. In this study, the objective was to investigate whether baseline values of VO2peak, body mass index (BMI), time spent in moderate- to vigorous-intensity physical activity (MVPA), physical fatigue, age, chemotherapy treatment, and the adherence to the endurance training moderated the effect of HI vs. LMI exercise on VO2peak. Materials and Methods We used data collected from a subsample from the Phys-Can RCT; women who were diagnosed with breast cancer and had a valid baseline and post-intervention VO2peak test were included (n = 255). The exercise interventions from the RCT included strength and endurance training at either LMI, which was continuous endurance training at 40 – 50 % of heart rate reserve (HRR), or at HI, which was interval training at 80–90% of HRR, with similar exercise volume in the two groups. Linear regression analyses were used to investigate moderating effects using a significance level of p \u3c 0.10. Statistically significant interactions were examined further using the Johnson–Neyman (J-N) technique and regions of significance (for continuous variables) or box plots with adjusted means of post-intervention VO2peak (for binary variables). Results Age, as a continuous variable, and adherence, dichotomized into \u3c or \u3e 58% based on median, moderated the effect of HI vs. LMI on CRF (B = −0.08, 95% CI [−0.16, 0.01], pinteraction = 0.06, and B = 1.63, 95% CI [−0.12, 3.38], pinteraction = 0.07, respectively). The J-N technique and regions of significance indicated that the intervention effect (HI vs. LMI) was positive and statistically significant in participants aged 61 years or older. Baseline measurement of CRF, MVPA, BMI, physical fatigue, and chemotherapy treatment did not significantly moderate the intervention effect on CRF. Conclusion Women with breast cancer who are older and who have higher adherence to the exercise regimen may have larger effects of HI exercise during (neo-)adjuvant cancer treatment on CRF

Moderators of resistance-based exercise programs\u27 effect on sarcopenia-related measures in men with prostate cancer previously or currently undergoing androgen deprivation therapy: An individual patient data meta-analysis

Introduction: Older men with prostate cancer are commonly affected by reductions in lean mass and physical function following androgen deprivation therapy (ADT). Resistance-based exercise programs are critical to counteract the musculoskeletal toxicities derived from prostate cancer treatment and aging. However, there is significant variability in the effects of exercise interventions. Examining demographic and clinical moderators of exercise effects in this patient group can assist in identifying which subgroups of patients benefit most. Therefore, we examined the effects and moderators of resistance-based exercise programs on sarcopenia-related outcomes that included lean mass, skeletal muscle index, physical function, and muscle strength in older men with prostate cancer. Materials and Methods: Data were retrieved from the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium. For the present study, we included data from trials that examined the effects of supervised resistance-based exercise interventions on lean mass outcomes, muscle strength, and physical function in patients with prostate cancer previously or currently treated with ADT. Linear mixed models were undertaken to analyse the effects of resistance-based exercise programs considering the clustering of patients within studies. Effects were evaluated by regressing the study group on the post-intervention value of the outcome adjusted for the baseline value, while potential moderators were examined by adding the moderator and its interaction term into the regression model. Results: A total of 560 patients with prostate cancer (age: 69.5 ± 7.8 yrs.; body mass index: 28.6 ± 4.0 kg.m−2) previously or currently treated with ADT were included. Resistance-based exercise programs resulted in significant effects on whole-body and appendicular lean mass and the skeletal muscle index (P \u3c 0.05), with improvements observed across different characteristics. Improvements were also observed in 400-m walk and 6-m backwards tandem walk (P \u3c 0.05), with patients presenting with lower baseline levels deriving greater exercise effects on 400-m walk (−19.4 s, 95% confidence interval [CI]: −36.6 to −2.3) and 6-m backwards tandem walk tests (−3.0 s, 95% CI: −5.7 to −0.3). For relative muscle strength, significant exercise effects were observed, with greater effects in younger patients (0.35 kg.kg−1, 95% CI: 0.22 to 0.48). Discussion: Resistance-based exercise programs effectively improve well-known markers of sarcopenia in men with prostate cancer, with specific subgroups of patients, such as those younger and presenting with lower baseline levels of physical function, deriving greater effects on muscle strength and physical function, respectively

Return to work experiences of patients treated with stem cell transplantation for a hematologic malignancy

Purpose This qualitative study aimed to identify hematopoietic stem cell transplantation (HSCT) survivors’ (1) work perceptions; (2) barriers to and facilitators of return to work (RTW); and (3) possible solutions to improve RTW. Method Fifteen patients treated with HSCT 1–5 years ago participated in face-to-face semi-structured interviews. Interviews were analyzed following the steps of thematic content analyses. Results RTW was often characterized as a complex and prolonged trajectory, and it was frequently incomplete in working hours, tasks, and/or responsibilities. Work perceptions varied between patients; most valued work as positive, but some also reported a decline in work capacity and/or in importance. Perceived barriers included the duration and side effects of cancer treatment, the presence of comorbidity and poor health before diagnosis, having difficulties commuting and doing household tasks. Perceived facilitators were financial incentives, keeping in touch with the workplace, support of other patients and family, and looking after one’s health. Proposed solutions to improve RTW included discussing RTW at the hospital, enhanced employer support, improved accessibility of rehabilitation programs, and more information about the consequences of being sick-listed. Conclusions Many HSCT survivors value work as important and they are motivated to RTW. Insight in work perceptions, RTW barriers, and solutions might help researchers, healthcare professionals, and employers to develop and/or tailor individualized multidisciplinary care to facilitate RTW

Return to work experiences of patients treated with stem cell transplantation for a hematologic malignancy

Purpose This qualitative study aimed to identify hematopoietic stem cell transplantation (HSCT) survivors’ (1) work perceptions; (2) barriers to and facilitators of return to work (RTW); and (3) possible solutions to improve RTW. Method Fifteen patients treated with HSCT 1–5 years ago participated in face-to-face semi-structured interviews. Interviews were analyzed following the steps of thematic content analyses. Results RTW was often characterized as a complex and prolonged trajectory, and it was frequently incomplete in working hours, tasks, and/or responsibilities. Work perceptions varied between patients; most valued work as positive, but some also reported a decline in work capacity and/or in importance. Perceived barriers included the duration and side effects of cancer treatment, the presence of comorbidity and poor health before diagnosis, having difficulties commuting and doing household tasks. Perceived facilitators were financial incentives, keeping in touch with the workplace, support of other patients and family, and looking after one’s health. Proposed solutions to improve RTW included discussing RTW at the hospital, enhanced employer support, improved accessibility of rehabilitation programs, and more information about the consequences of being sick-listed. Conclusions Many HSCT survivors value work as important and they are motivated to RTW. Insight in work perceptions, RTW barriers, and solutions might help researchers, healthcare professionals, and employers to develop and/or tailor individualized multidisciplinary care to facilitate RTW

Associations of fat and muscle mass with overall survival in men with prostate cancer: A systematic review with meta-analysis

Background To systematically review and analyse the associations between fat and muscle mass measures with overall survival in men with prostate cancer. Methods A systematic search was conducted in CINAHL, Cochrane Library, EMBASE, PubMed, and Web of Science databases from inception to December 2020, while abstracts from the American Society of Clinical Oncology (ASCO), Clinical Oncology Society of Australia (COSA), and the American College of Sports Medicine (ACSM) conferences were searched from 2014 to 2020. Eligible articles examined the association of body composition measures, such as fat mass (e.g., fat mass, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT) and muscle mass measures, with overall survival in prostate cancer patients at any treatment stage. The primary endpoint was overall survival. Random-effect meta-analysis was conducted for studies reporting multivariable or univariable analysis assessing the associations of fat mass measures (i.e., fat mass, VAT, SAT, VAT/SAT) and muscle mass measures with overall survival. Results Sixteen cohort studies that comprised 4807 men with prostate cancer were included. Total adiposity (hazard ratio (HR) 0.98, 95% CI: 0.75–1.28, p = 0.888) and VAT (HR 1.03, 95% CI: 0.74–1.43, p = 0.873) were not significantly associated with overall survival, while higher subcutaneous adipose tissue levels were associated with higher survival (HR 0.68, 95% CI: 0.54–0.84, p = 0.001). Greater mortality risk was found in patients with localised (HR 1.91, 95% CI: 1.40–2.62, p \u3c 0.001) and advanced disease (HR 1.43, 95% CI: 1.07–1.92, p = 0.020) presenting with low levels of muscle mass compared to those presenting with high levels. Discussion These results indicate that although overall adiposity should be cautiously interpreted in regards to survival, high muscle mass and SAT, and low VAT/SAT ratio values are associated with overall survival in men with prostate cancer

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 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

Higher Muscle Strength Is Associated with Prolonged Survival in Older Patients with Advanced Cancer

BACKGROUND: Identifying predictors of treatment toxicity and overall survival (OS) is important for selecting patients who will benefit from chemotherapy. In younger patients with cancer, muscle mass and radiodensity are associated with treatment toxicity and OS. In this study, we investigated whether muscle mass, radiodensity, and strength were associated with treatment toxicity and OS in patients with advanced cancer aged 60 years or older. MATERIALS AND METHODS: Before starting palliative chemotherapy, muscle mass and radiodensity were assessed using computed tomography scans and muscle strength was assessed using a hydraulic hand grip dynamometer. Treatment toxicity was defined as any toxicity resulting in dose reduction and/or discontinuation of treatment. Multiple logistic and Cox regression analyses were performed to study potential associations of muscle mass, radiodensity, and strength with treatment toxicity and OS, respectively. RESULTS: The participants were 103 patients, with a mean age of 70 years, with advanced colorectal, prostate, or breast cancer. Muscle parameters were not significantly associated with treatment toxicity. Higher muscle strength was associated with longer OS (hazard ratio 1.03; 95% confidence interval 1.00-1.05). Muscle mass and radiodensity were not significantly associated with OS. CONCLUSION: Higher muscle strength at the start of palliative chemotherapy is associated with significantly better OS in older patients with advanced cancer. None of the investigated muscle parameters were related to treatment toxicity. Future studies are needed to evaluate whether muscle strength can be used for treatment decisions in older patients with advanced cancer. IMPLICATIONS FOR PRACTICE: This study in older patients with advanced cancer showed that adequate muscle strength is associated with longer overall survival. The results of this study imply that muscle strength might be helpful in estimating survival and therefore in identifying older patients who will benefit from anticancer treatment

Association between energy balance-related factors and clinical outcomes in patients with ovarian cancer: A systematic review and meta-analysis

Background: This systematic review and meta-analysis synthesized evidence in patients with ovarian cancer at diagnosis and/or during first-line treatment on; (i) the association of body weight, body composition, diet, exercise, sedentary behavior, or physical fitness with clinical outcomes; and (ii) the effect of exercise and/or dietary interventions. Methods: Risk of bias assessments and best-evidence syntheses were completed. Meta-analyses were performed when ≥ 3 papers presented point estimates and variability measures of associations or effects. Results: Body mass index (BMI) at diagnosis was not significantly associated with survival. Although the following trends were not supported by the best-evidence syntheses, the meta-analyses revealed that a higher BMI was associated with a higher risk of post-surgical complications (n = 5, HR: 1.63, 95 % CI: 1.06 – 2.51, p = 0.030), a higher muscle mass was associated with a better progression-free survival (n = 3, HR: 1.41, 95 % CI: 1.04 – 1.91, p = 0.030) and a higher muscle density was associated with a better overall survival (n = 3, HR: 2.12, 95 % CI: 1.62 – 2.79, p \u3c 0.001). Muscle measures were not significantly associated with surgical or chemotherapy-related outcomes. Conclusions: The prognostic value of baseline BMI for clinical outcomes is limited, but muscle mass and density may have more prognostic potential. High-quality studies with comprehensive reporting of results are required to improve our understanding of the prognostic value of body composition measures for clinical outcomes. Systematic review registration number: PROSPERO identifier CRD42020163058