Serum PTHrP predicts weight loss in cancer patients independent of hypercalcemia, inflammation, and tumor burden

Context: Recent animal studies showed that tumor-derived PTHrP induced cancer cachexia by fat browning with increased energy expenditure; however, clinical evidence from human data is insufficient. Objective: We investigated whether serum PTHrP levels independently predicts weight loss (WL) in cancer patients. Design, Setting, and Patients: From a longitudinal observational cohort, body mass index (BMI) of patients with measured serum PTHrP levels (n = 624) was assessed (median follow-up of 327 d). Main Outcome Measures: Cox hazard models were used to examine the predictive value of PTHrP for WL defined by consensus definition (WL [consensus], percentage WL <-5% or percentage WL <-2% plus BMI < 20 kg/m2) and by BMI-adjusted grades (WL [BMI adjusted]). Results: The overall risk of WL (consensus) was 34.4%. Compared with PTHrP-negative subjects, patients with higher PTHrP levels (PTHrP = median 5.7 pmol/L) had more WL (percentage WL,-6.9% vs-1.1%, P=.010) at follow-up.Ahigher PTHrP level was associated with an increased loss of body weight (<=-2.73), muscle (<=-1.85), and fat (<=-2.52) after controlling for age, sex, and BMI. Kaplan-Meier analysis demonstrated that subjects with higher PTHrP had increased WL risk compared with lower PTHrP or PTHrP-negative groups (52.0% vs 38.9% vs 29.7%, P <.001). Serum PTHrP was independently associated with an increased WL risk (hazard ratio [HR]1.23, P =.005) adjusted for potent predictors including serum levels of calcium, C-reactive protein, albumin, cancer stage, and performance status of patients. Consistent results were observed when BMIadjusted WL was applied. Conclusions: Serum PTHrP levels predicted cancer-associated WL independent of the presence of hypercalcemia, inflammation, tumor burden, and other comorbidities.