Physical exercise is increasingly recognized as a valuable treatment strategy in managing prostate cancer, not only enhancing supportive care but potentially influencing disease outcomes. However, there are limited studies investigating mechanisms of the tumor-suppressive effect of exercise. Recently, extracellular vesicles (EVs) have been recognized as a therapeutic target for cancer as tumor-derived EVs have the potential to promote metastatic capacity by transferring oncogenic proteins, integrins, and microRNAs to other cells and EVs are also involved in developing drug resistance. Skeletal muscle has been identified as an endocrine organ, releasing EVs into the circulation, and levels of EV-containing factors have been shown to increase in response to exercise. Moreover, preclinical studies have demonstrated the tumor-suppressive effect of protein and microRNA contents in skeletal muscle-derived EVs in various cancers, including prostate cancer. Here we review current knowledge of the tumor-derived EVs in prostate cancer progression and metastasis, the role of exercise in skeletal muscle-derived EVs circulating levels and the alteration of their contents, and the potential tumor-suppressive effect of skeletal muscle-derived EV contents in prostate cancer. In addition, we review the proposed mechanism of exercise in the uptake of skeletal muscle-derived EVs in prostate cancer.

[This corrects the article DOI: 10.3389/fphys.2019.00843.].

Introduction: Androgen deprivation therapy (ADT) is considered the basic treatment for advanced prostate cancer, but it is highly associated with detrimental changes in muscle mass and muscle strength. The aim of this meta-analysis was to investigate the effects of supervised physical training on lean mass and muscle strength in prostate cancer patients undergoing ADT. Methods: A systematic literature search was performed using MEDLINE, Embase, and ScienceDirect until October 2018. Only studies that examined both muscle mass and strength in prostate cancer patients undergoing ADT were included. Outcomes of interest were changes in lean body mass (surrogate for muscle mass) as well as upper and lower body muscle strength. The meta-analysis was performed with fixed-effects models to calculate mean differences between intervention and no-training control groups. Results: We identified 8,521 publications through the search of the following key words: prostate cancer, prostate tumor, prostate carcinoma, prostate neoplasm, exercise, and training. Out of these studies, seven randomized controlled trials met the inclusion criteria and where included in the analysis. No significant mean differences for changes in lean mass were observed between the intervention and control groups (0.49 kg, 95% CI: -0.76, 1.74; P = 0.44). In contrast, the mean difference for muscle strength was significant both in chest (3.15 kg, 95% CI: 2.46, 3.83; P < 0.001) and in leg press (27.46 kg, 95% CI: 15.05, 39.87; p < 0.001). Conclusion: This meta-analysis provides evidence that low- to moderate-intensity resistance and aerobic training is effective for increasing muscle strength but may not be sufficient to affect muscle mass in prostate cancer patients undergoing ADT. The underlying mechanisms for this maladaptation may in part be explained by an insufficient stimulus induced by the training regimens as well as a delayed initiation of training in relation to the start of ADT. When interpreting the present findings, one should bear in mind that the overall number of studies included in this review was rather low, emphasizing the need for further studies in this field.

This review and meta-analysis aimed to evaluate the effects of high-intensity interval training (HIIT) compared to usual care (UC) or moderate-intensity training (MIE) on physical fitness and health-related outcomes in cancer patients across all stages of therapy and aftercare.
Databases were systematically searched in accordance with the PRISMA guidelines until October 4th, 2018. Eligibility criteria included adult patients of various cancer types, performing HIIT vs. UC or MIE. Outcomes of interest included physical fitness (cardiorespiratory fitness [VO2peak] and functional capacity) and health-related outcomes (body composition, quality of life, cancer-related fatigue, and blood-borne biomarkers). Mean differences (MD) were calculated and pooled to generate effect sizes for VO2peak.
The search identified 1453 studies, out of which 12 articles were included. The average duration of interventions was 6.7 ± 3.0 weeks, with 2.8 ± 0.5 sessions per week. The meta-analysis for VO2peak showed superiority of HIIT compared to UC (MD 3.73; 95% CI 2.07, 5.39; p < 0.001) but not MIE (MD 1.36; 95% CI - 1.62, 4.35; p = 0.370). Similarly, no superior effects of HIIT compared to MIE were found for quality of life or changes in lean mass, while evidence was provided for a larger reduction in fat mass.
This systematic review showed that short-term HIIT induces similar positive effects on physical fitness and health-related outcomes as MIE but seems to be superior compared to UC. Thus, HIIT might be a time-efficient intervention for cancer patients across all stages of therapy and aftercare.
High-intensity interval training (HIIT) is superior compared to usucal care in improving physical fitness and health-related outcomes in cancer patients across all stages of therapy and aftercare. Currently, there is no evidence for the benefits of HIIT compared to aerobic training of moderate intensity (MIE) for changes in cardiorespiratory fitness, lean mass and patient-reported outcomes. Reductions in fat mass may be more pronounced in HIIT compared to MIE when training is performed in aftercare.