A randomized controlled trial on the effectiveness of strength training on clinical and muscle cellular outcomes in patients with prostate cancer during androgen deprivation therapy: rationale and design

Lene Thorsen, Tormod S Nilsen, Truls Raastad, Kerry S Courneya, Eva Skovlund, Sophie D Fosså, Lene Thorsen, Tormod S Nilsen, Truls Raastad, Kerry S Courneya, Eva Skovlund, Sophie D Fosså

Abstract

Background: Studies indicate that strength training has beneficial effects on clinical health outcomes in prostate cancer patients during androgen deprivation therapy. However, randomized controlled trials are needed to scientifically determine the effectiveness of strength training on the muscle cell level. Furthermore, close examination of the feasibility of a high-load strength training program is warranted. The Physical Exercise and Prostate Cancer (PEPC) trial is designed to determine the effectiveness of strength training on clinical and muscle cellular outcomes in non-metastatic prostate cancer patients after high-dose radiotherapy and during ongoing androgen deprivation therapy.

Methods/design: Patients receiving androgen deprivation therapy for 9-36 months combined with external high-dose radiotherapy for locally advanced prostate cancer are randomized to an exercise intervention group that receives a 16 week high-load strength training program or a control group that is encouraged to maintain their habitual activity level. In both arms, androgen deprivation therapy is continued until the end of the intervention period.Clinical outcomes are body composition (lean body mass, bone mineral density and fat mass) measured by Dual-energy X-ray Absorptiometry, serological outcomes, physical functioning (muscle strength and cardio-respiratory fitness) assessed with physical tests and psycho-social functioning (mental health, fatigue and health-related quality of life) assessed by questionnaires. Muscle cellular outcomes are a) muscle fiber size b) regulators of muscle fiber size (number of myonuclei per muscle fiber, number of satellite cells per muscle fiber, number of satellite cells and myonuclei positive for androgen receptors and proteins involved in muscle protein degradation and muscle hypertrophy) and c) regulators of muscle fiber function such as proteins involved in cellular stress and mitochondrial function. Muscle cellular outcomes are measured on muscle cross sections and muscle homogenate from muscle biopsies obtained from muscle vastus lateralis.

Discussion: The findings from the PEPC trial will provide new knowledge on the effects of high-load strength training on clinical and muscle cellular outcomes in prostate cancer patients during androgen deprivation therapy.

Trial registration: ClinicalTrials.gov: NCT00658229.

Figures

Figure 1
Figure 1
A schematic drawing of a muscle fiber (muscle cell) in longitudinal- and cross sectional plane. The muscle fiber is surrounded by two membranes, the plasma membrane (inner) and the basal lamina (outer). The satellite cells are located between these two membranes, and just beneath the plasma membrane lays the myonuclei. The contractile proteins in the muscle cell are arranged in myofibrils. In the longitudinal plane you see that the myofibrils are organized into sarcomeres separated by the z-disc and the mitochondria are seen as circular spots between the myofibrils.
Figure 2
Figure 2
Schematic muscular adaptations to strength training in healthy men and PC patients on ADT. Schematic muscular adaptations to strength training in healthy men (A), possible consequences of ADT on muscle fibers in PC patients (B), and possible muscular adaptations to strength training in PC patients on ADT (C). In A), the muscle fiber cross sectional area is increased as a result of an increase in the number and size of myofibrils within the muscle fiber, and this increase in size is supported by an increased number of satellite cells and (often) increased number of myonuclei. In B), ADT results in decreased muscle fiber cross sectional area and reduced muscle function. In C), muscle fiber cross sectional area and muscle function is normalized in ADT treated PC patients on strength training.
Figure 3
Figure 3
Timeline in the PEPC trial. Different duration of ADT related to different risk groups and somehow different treatment strategies in the two hospitals. Importantly all patients are on ADT at pre- and post-intervention assessments.

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