Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis

Abstract Background: In 2013, denosumab was introduced as peri-operative adjuvant treatment for giant cell tumor (GCT) of bone as it inhibits osteoclast activity. It is suggested that denosumab relives pain, facilitate curettage in lesions requiring resection initially. However, controversy remains whether denosumab increases the risk of local recurrence after surgery. Methods: Medline, Embase and the Cochrane Library were comprehensively searched in June 2019 to identify studies investigating the clinical outcome of GCT of bone with and without peri-operative denosumab after surgery. Data were gathered and a meta-analysis was conducted. Result: Ten studies with 1082 cases (169 in denosumab group, 913 in control group) were included. Overall, denosumab was associated with significantly higher risk of recurrence(P<0.02) and inferior 5 year recurrence free survival(P=0.000). Denosumab and curettage has a relatively higher risk of recurrence comparing to curettage alone(P=0.07). The risk of recurrence is not significantly increased if denosumab was administered both preoperatively and postoperatively(P=0.24). Conclusion: Administration of denosumab is associated with increased risk of recurrence due to a variety of reasons, though it is proven effective in relieving pain, enabling curettage and improved functional outcome. Post-operative denosumab is recommended as it continuously suppress/eliminate residue tumor cells.