Pilot trial of physical and cognitive changes related to fall risk in enzalutamide patients with castration-resistant prostate cancer (CRPC).
Authors: Rodriguez Victor , Cameron Michelle , Winters-Stone Kerri M. , Beer Tomasz M. , Alumkal Joshi J. , Cetnar Jeremy Paul , Thawani Rajat , Amery Taylor , Vuky Jacqueline , Bailey Shawna , Graff Julie N 
Published: June 2022

e17018 Background: Advanced prostate cancer disproportionally affects older men (age ≥ 75 years). Despite representing only 26% of diagnoses, older men represent half of those diagnosed with metastatic disease and half of all prostate cancer deaths. Treatment options for CRPC include enzalutamide (enza), a competitive inhibitor of the androgen receptor, which shows improved overall survival and other cancer-specific responses in older men. However, enza is also reportedly associated with increased fall frequency of unclear pathophysiology. This pilot study examines strength, balance, and cognition in men before and 12 weeks after starting enza therapy for CRPC. Methods: This prospective single-arm study included men about to begin enza for CRPC, ≥ 65 years, able to ambulate independently. The following tests were administered at baseline and 12 weeks after initiation of enza: Sit-to-stand test (STS), Timed-Up-and-Go test, proprioception assessment, computerized dynamic posturography including sensory organization test (SOT), motor control test (MCT), and limits of stability; Functional Assessment of Cancer Therapy-Prostate, BPI-SF, Activities-specific Balance Confidence (ABC), Montreal Cognitive Assessment (MoCA), International Physical Activity Questionnaire (IPAQ), and the Godin leisure-time exercise questionnaire (GLTEQ). Falls were assessed with self-report fall diaries and calls from study team to participants over the course of 12 months. Results: Twenty-five participants enrolled. Median age was 75 years. There were 23 (92%) with both baseline and 12-week assessments, and 21 (84%) participants had complete falls data. From baseline to the 12-week follow up, ABC scale scores decreased (median 90.4 to 85.2), GLTEQ scale scores decreased (median 31.4 to 28.0), and time sitting per day from IPAQ increased (4 hours to 5 hours). Of those evaluable for falls, 15 (71%) did not fall during the 12 months and 6 (29%) fell at least once. The fallers and non-fallers did not differ with respect to age or MoCA scores at baseline and on re-assessment. Those who fell performed more poorly on the STS test, the ABC and the dynamic posturography evaluations. Those who fell also had a higher level of activity by GLTEQ. Conclusions: This pilot study does not clearly elucidate the pathophysiology of falls in older men with CRPC taking enza but does provide useful and important guidance for the design of future studies in this area. Baseline and 12-week testing should be repeated at the 24-week time-point to allow for sufficient exposure to enza. To avoid confounding by practice effects, physical tests, particularly dynamic posturography, should be performed at least once prior to baseline assessment. Further research is needed to understand the mechanisms underlying the increased risk of falls previously observed in older men with CPRC taking enza.