Parathyroid hormone–related peptide and survival of patients with cancer and hypercalcemia

Abstract Purpose Parathyroid hormone–related peptide (PTHrP) is the predominant cause of malignancy-associated hypercalcemia. However, its prognostic utility is unclear. We aimed to determine the prognostic value of serum PTHrP levels in patients who had hypercalcemia associated with malignancy. Methods In this prospective case series, we evaluated 76 patients with a diagnosis of cancer and hypercalcemia (serum calcium level ≥10.3 mg/dL on at least two occasions). PTHrP levels ≥1 pmol/L were considered elevated. We used multivariate Cox regression analysis to identify factors associated with mortality. Results Fifty patients (66%) died during follow-up. In a multivariate analysis, higher pretreatment calcium levels and elevated PTHrP levels were associated with increased mortality, with effects of PTHrP varying by age (P = 0.03). Survival was associated with pretreatment calcium levels both in patients over 65 years of age (hazard ratio [HR] per mg/dL = 1.5; 95% confidence interval [CI]: 1.2 to 1.8; P<0.001) and in patients aged 65 years or less (HR = 1.3; 95% CI: 1.1 to 1.5; P = 0.003). Adjusted for pretreatment calcium levels, elevated PTHrP levels were associated with increased mortality in patients aged ≤65 years (HR = 3.8; 95% CI: 1.6 to 8.8; P = 0.002), but not in older patients (HR = 0.7; 95% CI: 0.3 to 1.9; P = 0.51). Conclusion PTHrP is a useful prognostic factor in malignancy-associated hypercalcemia, at least in patients aged ≤65 years.