Elevated Allostatic Load, Adverse Body Composition, and Reduced Overall Survival in a Retrospective Cohort of Men...

Allostatic load (AL) is a biophysiological framework to measure chronic stress. Elevations in AL are adversely prognostic in breast and lung cancer.

To determine if higher AL at the time of diagnosis is adversely associated with cancer outcomes among men with newly diagnosed metastatic prostate cancer and to evaluate if substituting image-derived body composition measures for body mass index influences risk estimates of outcomes.

A retrospective cohort study design was utilized.

Demographic and clinical data of adult men (aged 18 years or older) diagnosed with histologically confirmed Stage IVb metastatic prostate cancer were collected from the electronic health record at a cancer center in the Midwest for patients. Data collection spanned January 2015 to June 2022. Alterations in body mass index and cardiovascular, metabolic, hematologic, renal, and immune function were used to calculate AL, assigning 1 point for values outside the acceptable clinical threshold (0 to 9 points possible). Diagnostic computed tomography images were used to precisely quantify body composition, specifically visceral adipose tissue, low muscle mass, and myosteatosis (ie, fatty infiltrated muscle). Men were followed until the date of death or censored at the last known follow-up. A total of 187 men were screened; 126 men were included in the primary analyses, and 114 contributed body composition data.

Progression-free survival and overall survival were modeled.

Frequencies (percentages) and medians (IQR) are used to describe patient characteristics and AL, and time to event analyses (hazard ratios [HRs] and 95% CI) are presented.

Body mass index (79%), hemoglobin level (57%), and glucose level (39%) were the most prevalent alterations in AL scoring. Median AL was 3 points (IQR = 2 to 4). Increasing AL was associated with increased hazard of death (HR 1.25; 95% CI, 1.02 to 1.53; P = .029), after adjusting for age, race and ethnicity, smoking, and treatment. Significant associations with increasing AL and increased hazard of death were also detected when visceral adipose tissue (HR 1.44; 95% CI, 1.15 to 1.81; P = .001), myosteatosis (HR 1.52; 95% CI, 1.20 to 1.92; P = .001) or low muscle mass (HR 1.59; 95% CI, 1.26 to 2.00; P < .001) were substituted for body mass index in the AL framework. Multivariable modeling supports that AL is also significantly associated with increased hazard of disease progression (HR 1.25; 95% CI, 1.04 to 1.50; P = .018), when body mass index was replaced with low muscle mass.

This study establishes the clinical relevance of AL for men with newly diagnosed metastatic prostate cancer and the influence of body composition in this context. Because body mass index, hemoglobin level, and glucose level were the primary drivers of higher AL scores, these may reflect important targets of future nutrition interventions to improve metabolic health and cancer outcomes.