The results of this study have demonstrated that older men with prostate cancer receiving long-term ADT exhibit significant functional and physical impairment and are at risk of falls. Nearly one half of men were impaired according to the IADLs and VES-13 scores, which portend an increased risk of mortality.11,12
We also found significant impairment in physical performance measures.13,14
The mean score on SPPB was 7.9, lower than the mean of 10.4, which has been reported elsewhere in similarly aged men not receiving ADT.20
The impairments were noted for all measures of the SPPB: balance, walking speed, and chair stands. In addition, 22% reported falls during the previous 3 months, more than double the 6.6%–9.0% of older men who reported falls within 3–4 months in general outpatient geriatric populations.21,22
It is plausible that the combination of low bone density and increased falls could contribute to the increased risk of fractures noted in this population. Our results suggest that a vulnerable cohort of elderly patients receiving ADT who are seen routinely in clinics. Larger prospective trials are needed to clarify the relationship of ADT to physical disability and falls in this patient population.
Only a few other studies have reported the prevalence of objective physical disability in older patients with prostate cancer, and none of these studies reported on the prevalence of falls. In a sample of patients with prostate cancer at any stage, significant functional and physical disabilities were reported.23
However, this was a heterogeneous population with advanced prostate cancer and many had received treatments other than ADT. In this sample, 50% of patients had abnormal scores on the Performance-Oriented Assessment of Mobility, indicating a risk of falls, although the prevalence of falling was not reported.24
Another study reported no significant differences in physical function between patients with nonmetastatic prostate cancer receiving ADT and controls.25
Physical function was tested with the 6-meter walk26
and the Timed Up and Go test.27
However, the age of patients was much younger (50% of the prostate cancer group was younger than 73 years old).
This study did have limitations. First, this was a small convenience sample, limiting our ability to generalize our findings. Second, confounding factors were present that could have contributed to our findings that were not evaluated in our study, such as vitamin D deficiency.28
Vitamin D deficiency is prevalent in older men, especially in those who are African American, and has been associated with decreased muscle strength and an increased risk of falling.29,30
However, in our cohort, all patients were recommended to take calcium (1000–1500 mg) and vitamin D (800 IU),31
and most scored well on the nutritional assessment. Third, objective measures of muscle mass were not performed; thus we were unable to comment on the correlation of muscle mass to our findings of impairment in this patient population. Also, because of the short follow-up, we were unable to draw significant conclusions on the change in physical performance and falls with time in this patient population. Finally, this was a cross-sectional study; thus we could not establish a temporal relationship between ADT use and abnormal physical performance and falls. Nevertheless, the greater prevalence of falls and physical performance abnormalities in our study, compared with the general geriatrics population, is concerning.
This concern is especially noteworthy given the increasing attention to the high-risk geriatric state of “frailty.” Frailty is a well-characterized syndrome that can be measured with simple clinical and physiologic markers that develops over time as a result of accumulated stressors.32
Frailty is predictive of incident falls, worsening mobility, increased hospitalizations, and greater mortality in the general geriatric population.33
Given the marked mobility and physical deficit problems found in older men with prostate cancer receiving ADT, we have hypothesized that ADT might “induce” frailty in these patients.34
It is tempting to hypothesize that men with prostate cancer and undergoing ADT develop frailty, in part, because of the accelerated muscle atrophy resulting from the treatment. Studies have shown that ADT is an independent contributor to the loss of lean muscle mass, with decreased muscle mass and strength demonstrated within the first few weeks of therapy.35–37
We acknowledge that the relative contribution of ADT to falls, physical disability, and frailty has not been determined in our uncontrolled study. The underlying cause of these abnormalities is complex and often multifactorial. Still, we did find that, whatever the underlying cause, older men undergoing ADT are falling at high rates and are markedly physically disabled.
Recognizing the morbidity and mortality associated with fractures, physicians caring for this patient population should consider routinely screening for abnormal physical performance and falls. Additional controlled studies are necessary to determine the effect ADT has on the development of frailty and physical disability. In addition, further study of the effect of interventions on preventing or reducing falls and physical dysfunction in elderly men undergoing ADT is imperative.