Abstract / Summary
ABSTRACT Background Cachexia is a multifactorial muscle wasting syndrome and is responsible for 20%–40% of cancer‐related deaths, yet no FDA‐approved therapies exist. Preclinical studies suggest that metastatic bone disease may contribute to muscle wasting, but this relationship has not been evaluated in clinical populations. This study evaluated whether metastatic bone disease at diagnosis is associated with longitudinal skeletal muscle loss and whether metastatic bone disease and longitudinal skeletal muscle loss are associated with overall survival in patients with kidney cancer. Methods A total of 293 patients (66.9% male, 33.1% female, median age 60 years) were retrospectively identified with either localised kidney cancer, extraosseous metastatic disease, or osseous metastatic disease at diagnosis. Clinical and demographic variables and treatments were recorded. Body composition was quantified over time for a subset by body mass index (BMI) ( N = 221) and CT analysis at the L3 vertebral level ( N = 99). Longitudinal changes were analysed using linear regression, and overall survival was assessed with Kaplan–Meier and multivariable Cox proportional hazards models. Results Patients with osseous metastatic disease had a reduction in BMI over time compared with those with localised or extraosseous metastatic disease (median of −3.6% per year, compared with +0.7% and −2.6% respectively, p < 0.01). Skeletal muscle loss was greatest for those with osseous metastasis (−7.5% per year, compared with −0.8% and −1.2% respectively, p < 0.01). Multivariable linear regression demonstrated osseous metastasis at diagnosis was strongly associated with muscle loss ( β coefficient of −20.9 [95% confidence interval (CI): −35.56 to −6.27]). In multivariable Cox regression analysis, osseous metastasis at diagnosis was associated with an increased risk of death (HR 15.8; 95% CI: 2.00 to 124.95; p < 0.01), as was longitudinal skeletal muscle loss (HR 1.02 for each 1% loss per year; 95% CI: 1.01 to 1.04; p < 0.01). Conclusions This study provides the first clinical evidence that metastatic bone disease is strongly associated with skeletal muscle loss and reduced survival in kidney cancer patients. These findings extend prior preclinical observations into the clinical setting and support further investigation into the possibility that tumour–bone–muscle interactions drive systemic muscle wasting. Importantly, the observation that severe muscle loss is strongly associated with mortality in kidney cancer highlights the need to consider cachexia as a modifiable determinant of outcomes, not just a byproduct of advanced disease.