The impact of home-based exercise prehabilitation on skeletal muscle mitochondrial function in patients awaiting curative surgery for cancer

Abstract Introduction Cancer cachexia is associated with poor surgical outcomes, including increased length of stay, morbidity and mortality. Cachexia is a complex multi-faceted pathological process consistently associated with energy imbalance via hypermetabolism. Beyond this, pre-clinical animal models suggest mitochondrial dysfunction to be an important component of cachexia, although this is unconfirmed in humans. This study aimed to investigate the mitochondrial function of pre-surgical cancer patients, and the impact of exercise prehabilitation on this. Methods This study was approved by an NHS research ethics committee (IRAS: 275264). Male patients awaiting surgery with curative intent for colorectal and prostate cancer were eligible, with healthy volunteers recruited for comparison. Muscle biopsies of vastus lateralis were taken before and after 4-weeks home-based exercise (3x/wk). Mitochondrial oxidative phosphorylation (OXPHOS) was analysed using high-resolution respirometry (Oroboros Instruments). Results Eleven cancer patients and 6 healthy volunteers were recruited. Cancer patients had significantly lower maximal coupled (44.49pmol/(s*mg) vs. 74.81pmol/(s*mg), p=0.004) and uncoupled (55.82pmol/(s*mg) vs. 100.00pmol/(s*mg), p<0.001) OXPHOS capacity compared to healthy controls. Exercise training significantly increased maximal coupled (44.10pmol/(s*mg) vs. 54.64pmol/(s*mg), p=0.045) and uncoupled (56.20pmol/(s*mg) vs. 71.96pmol/(s*mg), p=0.001) OXPHOS capacity in this cancer cohort. Conclusion Declines in mitochondrial function appear to play a role in cancer cachexia. Short-term exercise training, in keeping with target timeframes for surgery (i.e., <31-days from decision-to-treat), appears to attenuate these declines. Further work is needed to determine if declines in mitochondrial function are causative or reactive, and to identify optimal exercise regimes to mitigate these declines.