Total and Regional Changes in Body Composition in Metastatic Hormone-sensitive Prostate Cancer Patients Randomized to Receive Androgen Deprivation + Enzalutamide ± Zoledronic Acid. The BONENZA Study.

Background and objective: The reduction of lean body mass (LBM) and the increase of fat body mass (FBM) caused by androgen deprivation therapy (ADT) administered to prostate cancer patients are well known to lead to an increased risk of sarcopenia. The effects of the addition of androgen receptor pathway inhibitors (ARPIs) to ADT on body composition have not been studied thoroughly.

Methods: BONENZA (NCT03336983) is a prospective phase 2 trial in which metastatic hormone-sensitive prostate cancer patients were randomized to receive ADT plus enzalutamide with (EZ arm) or without (E arm) the addition of zoledronic acid. Total and regional body composition parameters were evaluated by dual-energy x-ray absorptiometry (DXA) scans at baseline and after 18 mo of therapy.

Key findings and limitations: Eighty-nine patients (46 from the EZ arm and 43 from the E arm) had paired DXA evaluation at both time points. After 18 mo of therapy, FBM increased by +22.8% (p < 0.001), LBM reduced by -6.7% (p < 0.001), and appendicular lean mass index (ALMI) decreased by -9.2% (p < 0.001). The increase in FBM varied considerably according to body districts: from +36.1% in the right arms (p < 0.001) to +3.7% in the head (p < 0.01). Similarly, the decrease in LBM ranged from -9.4% (p < 0.001) in the right arm to -6.4% (p < 0.001) in the trunk. None of the patients met the criteria for sarcopenic obesity; however, after 18 mo of treatment, 11.76% of patients had FBM >40.8%, 3.5% of patients had an ALMI of <5.5, and the ALMI/FBM ratio decreased by -23.9% (p < 0.001). Age and baseline LBM influenced these body composition changes significantly, with younger patients (<70 yr) and those with higher baseline LBM experiencing more marked changes.

Conclusions and clinical implications: Body composition undergoes a significant change with the addition of ARPIs to ADT, with an increase in FBM and a reduction in LBM, which are twice as high as those expected with ADT alone. DXA has been proved to be a reliable tool for monitoring body composition, and an assessment of district variations can aid in implementing individual-supervised physical exercise to prevent the risk of sarcopenic obesity.