Muscle mitochondria, function, mass, and quality of life in prostate cancer during androgen deprivation therapy

Abstract Prostate cancer (PCa) negatively impacts muscle mass, physical function, and patient-reported outcomes (PROs), while androgen deprivation therapy (ADT) exacerbates these effects. Mitochondria are important for muscle function but their role in PCa patients undergoing ADT is not well-established. Our study characterizes the relationship between muscle mass, strength, endurance, PROs, and mitochondria in PCa patients over six months of ADT. Prior to ADT, higher mitochondrial function and endurance are associated with better PROs; whereas higher appendicular lean mass (ALM) correlate with worse PROs. Greater baseline VO 2 peak and mitochondrial function predict smaller declines in ALM, muscle function, and PROs. Proteomics analysis indicates mitochondrial dysfunction and upregulation of extracellular matrix organization, inflammation and coagulation-related pathways with ADT. Our findings suggest that mitochondrial function plays a role in muscle endurance and PROs in PCa. These data may help select patients and outcomes for clinical trials. Future studies should test whether targeting mitochondria can improve physical function and PROs in PCa.