Prognostic significance of disordered calcium metabolism in hormone-refractory prostate cancer patients with metastatic bone disease

Abstract

Bone metabolic disruption that occurs in bone metastatic prostate cancer could lead to disturbances of calcium metabolism. The prognostic role of either hypocalcemia or hypercalcemia was assessed in a consecutive series of hormone-refractory bone metastatic prostate cancer patients. Serum calcium was measured in 192 patients. The presence of hypocalcemia and hypercalcemia was related with baseline biochemical and clinical characteristics and the role of these two calcium disturbances in predicting prognosis and adverse skeletal-related events (SREs) was assessed. As compared to normocalcemic patients, hypocalcemic patients (n ¼ 51) had higher tumor load in bone (P ¼ 0.005), higher plasma chromogranin A (CgA, P ¼ 0.01), serum alkaline phosphatase (P ¼ 0.01), urinary N-telopeptide (NTX, P ¼ 0.002) and lower hemoglobin values (P ¼ 0.01), while hypercalcemic patients (n ¼ 16) had higher plasma CgA (P ¼ 0.001) and serum lactate dehydrogenase values (P ¼ 0.001), higher bone pain (P ¼ 0.003) and a lower frequency of pure osteoblastic lesions (P ¼ 0.001). Hypercalcemia was significantly associated with poor prognosis: hazard ratio (HR), 1.9 (95% confidence Interval (CI) 1.2-3.3) and higher risk to develop SREs HR, 2.5 (95% CI 1.2-5.2, P ¼ 0.01), while hypocalcemia was not associated with poor prognosis. The prognostic role of hypercalcemia was maintained in multivariate analysis after adjusting for validated prognostic parameters: HR, 2.72 (95% CI 1.1-6.8, P ¼ 0.03). These data suggest that serum calcium levels should be taken into account in the clinical decision-making process of bone metastatic prostate cancer patients. Patients with asymptomatic hypercalcemia could benefit of a strict follow-up and an immediate bisphosphonate treatment. Further prospective clinical trials are needed to confirm this finding.

Risk Factors Contributing to the Development of Hypocalcemia after Zoledronic Acid Administration in Patients with Bone Metastases of Solid Tumor

“…It was reported that immediate bisphosphonate treatment could be beneficial for the prostate cancer patients with bone metastasis and asymptomatic hypercalcemia. 17) Our data may indicate clinical advantage for these patients regarding relatively safe continuation of ZDA therapy without hypocalcemia.…”

Benefits of use of zoledronic acid in carcinoma prostate bone metastases (zoledronic acid)

“…osteomimicry. Ova složena interakcija između koštane mikrookoline i ćelija karcinom dovodi do začaranog kruga koji indukuje progresiju koštanih metastaza 9,14,15 . Iako su kod CaP metastaze u kostima osteoblastnog tipa, dominira proces osteolize, koji se takođe neprestano odvija i to je neposredni uzrok nastanka skeletnih događaja.…”

“…Kompenzatorno povećanje sekrecije paratireoidnog hormona je odgovorno za pojačanu osteoklastnu aktivnost i na udaljenim mestima u kostima, nevezano od mesta samih metastaza. Treba napomenuti još jedan dodatni uzrok resorpcije kostiju, a to je jatrogena osteoporoza, kao posledica androgene deprivacione terapije 9,15,16 .…”

Management of Elderly Patients with Plasma Cell Myeloma

“…The CGA has been shown to help predict toxicity and mortality risk with cancer treatment, estimate survival, and detect problems not identified by age, performance status, and the initial history and physical examination [30,31,40]. It differs from the other risk-assessment tools in that it provides possible avenues to intervene to reduce treatment risk, e.g., reducing excessive medication use, addressing poor nutrition, etc., prior to or concurrent with starting cancer treatment [30,[41][42][43][44][45]. Despite the fact that the National Comprehensive Cancer Network (NCCN) and the International Society for Geriatric Oncology (SIOG) recommend using the CGA in any cancer patient age 65 years and older, widespread application of this tool has been difficult to achieve due to a need for specialist training and/ or extra time to complete the assessment [39,46].…”