Physical Exercise and Prostate Cancer (PEPC)

Prostate cancer (PCa) is the most common malignancy in men, and is at a locally advanced stage often treated with external beam radiotherapy and neoadjuvant or adjuvant androgen deprivation therapy (ADT). Although efficient in increasing disease free survival in PCa patients, ADT is associated with a number of side effects such as loss of muscle- and bone mass and increased fat mass. Some studies shows that strength training may be an efficient countermeasure to several of the known ADT-induced side effects, but additional randomized controlled trials are needed. Furthermore, no studies to date have investigated the effects of strength training on muscle cellular outcomes in PCa patients on ADT.

Time:

Place: Norges Idrettshøgskole

Formal title

Effect of strength training in prostate cancer patients undergoing androgen deprivation therapy

Formal

The main aim in the PEPC-trial was to investigate the effect of a 16-week strength training program on changes in lean body mass in PCa patients on ADT. Secondary endpoints were changes in fat mass and bone mineral density, muscle strength and daily function, as well as changes in muscle fiber cross sectional area, number of myonuclei and satellite cells in PCa patients on ADT.

Description

The PEPC-trial was a randomized controlled trial, where PCa patients undergoing ADT were recruited from two units at Oslo university hospital. Inclusion criteria were PCa patients younger than 75 years old scheduled to receive ADT throughout the intervention period, not suffering from conditions that where strength training could be contraindicated or that could complicate participation in the training program without major adjustments. Also, to ensure adherence to the intervention, patients were recruited from a geographical area limited to an estimated one-hour driving distance from the Norwegian School of Sport Sciences. After signing the informed consent form and after completing the baseline assessments (DXA, strength- and functional tests, questionnaires, and an optional muscle biopsy) the patients were computer randomised to either a strength training group for 16 weeks, or to a waiting list control group.

Result

Fifty-eight PCa patients under ADT were randomized to a strength training group (STG) (n=28) or a control group (CG) (n=30).

Contrary to our hypothesis we did not observe a significant increase in the total lean body mass (LBM) during the 16-week intervention. However, we did observe a significant increase in appendicular (upper- and lower extremities) LBM, when analysed separately. Interestingly, we did not observe any change in the trunk LBM, and our calculations based on results from a previous study in PCa patients on ADT shows the same trend. Muscles in the trunk have been shown to be particular sensitive to androgen supplementation, and one previous study have shown a higher number of myonuclei expressing androgen receptors in the m. trapezius compared to the m. vastus lateralis. Although this remains speculations, this may play a role in strength training adaptations during ADT. However, additional studies, using more direct measures of changes in muscle mass, are needed, as DXA may not be the optimal tool for evaluating changes in trunk LBM. Furthermore, it is worth mentioning that in a comparable trial conducted in healthy elderly men the increase in total LBM was approximately one third in the PCa patients on ADT, which showed large inter-subject variations. This highlights the need for individualized training programs in PCa rehabilitation.

We did not observe any changes in fat mass or in bone mineral density, However, our training program was successful in increasing performance in all strength tests and tests of daily function. 

At the muscle cellular level, our strength training intervention was successful in increasing the type II muscle fibre cross sectional area (CSA), but not the type I muscle fibre CSA. Since there are no comparable studies in PCa patients on ADT, we compared our results to studies in healthy elderly men, which generally show greater increases in type II fibre area than what we report. It is often reported that the number of myonuclei increase if the increase in CSA exceeds a certain threshold, and thus the myonuclear domain is kept relative constant. This was, however, not the case in the PEPC, where we observed an increased myonuclei number in type I fibres, where the CSA remained unchanged. The reason for this remains speculations, but a larger proportion of the myonuclei in type I fibres expresses androgen receptors compared to nuclei in the type II fibres. Thus, we speculate that ADT may induce greater stress in type I fibres compared to type II fibres. Our speculations are somewhat strengthen by a week tendency towards a reduced muscle fibre CSA in type I fibres within the CG. However, prospective studies investigating the effect of ADT on muscle cellular outcomes are needed before firm conclusions can be made. Also, the commonly reported increase in the number of satellite cells from strength training in healthy elderly men was not seen in the present study.

The design is published in BMC Cancer:

http://www.ncbi.nlm.nih.gov/pubmed/22458865

Results from the DXA scans and physical performance is published in Acta Oncologica:

http://www.ncbi.nlm.nih.gov/pubmed/25927504

Read the whole thesis

Download thesis