Role of (Neo)adjuvant Denosumab for Giant Cell Tumor of Bone

Denosumab is a RANK ligand inhibitor approved for the treatment of giant cell tumor of bone. While the role of denosumab in the setting of advanced and unresectable disease is well established, its role in surgically resectable disease is currently under discussion. Several prospective and retrospective series on neoadjuvant therapy in potentially resectable tumor with high morbidity surgery reported a relapse rate of 10-20% after resection and 30-40% after curettage. At the same time, less morbid surgery has obvious clinical advantages for the patient, and several studies have shown the efficacy of denosumab in downgrading of the surgical procedure. Currently, the role of neoadjuvant denosumab in operable GCTB is limited to selected cases in which a diffuse reactive bone formation and peripheral ossification can make an easier surgical procedure, for example, in tumors with a large soft tissue component. A planned resection may become less morbid when preoperative denosumab is administered. Whenever a segmental resection is thought to be indicated at diagnosis, denosumab may be considered in the neoadjuvant setting. A preoperative course of 6 months is considered safe and effective. Two case scenarios are presented and critically discussed. Because of the high recurrence rates after denosumab treatment followed by curettage, we discourage the use of denosumab when curettage is considered feasible. In this setting, a short course of preoperative denosumab (2-6 months) may be considered for highly selected cases, for example in pathological fractures. The role of adjuvant denosumab needs further investigation. Long-term disease control has been reported in case of non-surgical lesions, even after treatment interruption, but there is no consensus on ideal treatment duration and dosage for these scenarios. In all cases, multidisciplinary discussion with oncology, pathologist, radiologist, and surgeons is mandatory. Patient's comorbidities, dental conditions, and preferences, including family planning, should always be taken into account.