Parathyroid Hormone-related Peptide Is a Better Indicator of Cancer Treatment Efficacy Than Serum Calcium

BACKGROUND/AIM: Cancer-associated hypercalcemia is commonly a paraneoplastic manifestation of ectopic parathyroid hormone-related protein (PTHrP) production. Although serum calcium is routinely monitored, it can be influenced by antiresorptive therapy, albumin concentration, vitamin D status, and other clinical factors. Because durable control of hypercalcemia depends on effective anticancer therapy, serial PTHrP measurement may provide a more direct marker of treatment efficacy than serum calcium alone. CASE REPORT: A 66-year-old woman with extensive cutaneous squamous cell carcinoma (CSCC) of the scalp was considered unsuitable for primary surgical extirpation and was treated with the immune checkpoint inhibitor cemiplimab. While awaiting insurance approval, she was hospitalized with severe hypercalcemia. After one course of cemiplimab, both serum calcium and PTHrP were mildly elevated. After the second course, serum calcium fell to the low-normal range, whereas PTHrP rose markedly. Subsequent imaging showed rapid progression with metastases to the bone, brain, lung, and liver, and the patient died shortly thereafter. CONCLUSION: In progressive malignancy, PTHrP detected by immunoassay may increase even when serum calcium normalizes or declines. This case suggests that serial PTHrP levels may be more informative than serum calcium alone for assessing anticancer treatment efficacy in PTHrP-mediated hypercalcemia.