Unsurprisingly, according to a new article in the Journal of Clinical Oncology, long-term androgen deprivation therapy (ADT) is closely associated with loss of lean muscle mass (known as sarcopenia) in men being treated for prostate cancer. However, this appears to be the first time anyone has shown there is an age-related factor that is relevant to the degree of loss of lean muscle.
Smith et al. conducted a prospective evaluation of levels of lean muscle mass in a pre-specified subset of participants in a large, randomized, controlled clinical trial of denosumab to prevent fractures in men already receiving ADT for treatment of non-metastatic prostate cancer. Their study was based on an analysis of data from 252 patients — of whom 132 had been randomized to treatment with denosumab and 120 were randomized to a placebo.
All patients were scheduled to have their lean muscle mass measured at baseline and at 12, 24, and 36 months after initiation of treatment with ADT. To be eligible for evaluation, patients had to have a baseline lean muscle mass assessment and least one on-study assessment. In addition, patients were stratified by age (< 70 as opposed to ≥ 70 years) and by duration of ADT duration (≤ 6 as opposed to> 6 months) prior to trial enrollment.
Here are the key study findings:
- Average (median) duration of ADT was 20.4 months at study baseline.
- Average (mean) levels of lean muscle mass decreased significantly over time
- By 1 percent from baseline at month 12 (in 248 evaluable patients)
- By 2.1 percent from baseline at month 24 (in 205 evaluable patients)
- By 2.4 percent from baseline at month 36 (in 168 evaluable patients)
- Men ≥ 70 years of age (n= 127) had significantly greater changes in lean muscle mass than men < 70 years of age at all study time points.
- At 36 months, lean muscle mass decreased by 2.8 percent in men age ≥ 70 years and by 0.9 percent in men < 70 years. (P = .035).
- Prior time of exposure to ADT also affected the rate of loss of lean muscle mass during the course of the study.
- Men with ≤ 6 months of ADT at study entry (n = 36) lost 3.7 percent of lean muscle mass.
- Men with > 6 months of ADT at study lost only 0.9 percent of lean muscle mass.
The “New” Prostate Cancer InfoLink is actually surprised that the amount of lean muscle mass lost during the course of this study was as low as that reported. This would appear to confirm other data suggesting the importance of a good, regular exercise regimen for men on long-term ADT. Although other studies have shown loss of muscle mass over time among men with prostate cancer being treated with ADT, this study by Smith et al. appears to be a more thorough assessment of the risks than older studies.
Smith and his colleagues are careful to note that, since this study did not include a comparable group of men who did not receive ADT, it is impossible to determine how much of this loss of muscle mass is actually caused by the ADT and how much may be due to the simple fact (but complex effects) of aging.