The following is a summary of “A Systematic Review Supporting the Endocrine Society Clinical Practice Guideline on the Treatment of Hypercalcemia of Malignancy in Adults,” published in the March 2023 issue of Endocrinology & Metabolism by Seisa, et al.

Hypercalcemia is a common complication of malignancy, which is associated with high morbidity and mortality. To guide the treatment of hypercalcemia of malignancy in adults, the Endocrine Society developed a clinical practice guideline.

To support the development of the guideline, researchers conducted a systematic review of studies that addressed eight clinical questions prioritized by the guideline panel. In addition, they searched multiple databases and performed quantitative and qualitative synthesis. Finally, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of evidence.

They reviewed 1,949 citations and included 21 studies in their analysis. The risk of bias for most of the included studies was moderate. They found that a higher proportion of patients who received bisphosphonate achieved resolution of hypercalcemia compared to placebo. However, the incidence rate of adverse events was significantly higher in the bisphosphonate group. When comparing denosumab to bisphosphonate, they found no significant difference in the rate of patients who achieved resolution of hypercalcemia. Two-thirds of patients with refractory/recurrent hypercalcemia of malignancy who received denosumab following bisphosphonate therapy achieved resolution of hypercalcemia. Adding calcitonin to bisphosphonate therapy did not affect the resolution of hypercalcemia, time to normocalcemia, or hypocalcemia. However, only indirect evidence was available to address the management of hypercalcemia in tumors associated with high calcitriol levels, refractory/recurrent hypercalcemia of malignancy following bisphosphonates, and the use of calcimimetics in the treatment of hypercalcemia associated with parathyroid carcinoma. The certainty of the evidence to address all eight clinical questions was low to very low.

The systematic review provided evidence on the benefits and harms of treatments for hypercalcemia of malignancy. However, they noted that additional information about patients’ values and preferences and other important decisional and contextual factors were needed to facilitate the development of clinical recommendations.

Reference: academic.oup.com/jcem/article/108/3/585/6916875