Systemic Therapy in Patients with Resectable and Unresectable Cases of Giant Cell Tumor: A Systematic Review

Background: Giant cell tumor (GCT) is a common benign tumor of the appendicular and axial skeleton that represents 5% of all primary bone tumors. In recent years, the combination of conventional aggressive curettage with targeted adjuvant anti-osteoclastic agents including bisphosphonates and denosumab have led to lower recurrence rates in patients with GCT in a small number of retrospective case series. Furthermore, efficacy of the same anti-osteoclastic agents has been shown in cases of unresectable GCT of bone, leading to decreased rates of tumor progression and stabilization of disease. This review assesses whether the current literature weakly, moderately, or strongly supports a targeted systemic treatment as the standard of care in patients with GCT. Methods: We conducted a current search of the MEDLINE database for literature pertaining to systemic GCT treatment. Our inclusion criteria were as follows: 1) studies that reported on a series of patients with resectable or unresectable cases of GCT; 2) a subset of patients must have been treated with systemic bisphosphonate or RANK-L inhibitor therapy; 3) each series had a minimum of 10 patients with histopathologically confirmed GCT; 4) each series stated their follow-up period. Results: Overall 6 studies, reporting on a total of 487 patients, were selected for inclusion in this review. For analysis, these 6 retrospective studies were subdivided into series where all GCT patients had resectable tumors (n = 4) and series where patients had a mix of resectable and unresectable tumors (n = 2). The overall recurrence rate of GCT in patients with resectable tumors treated with adjuvant systemic bisphosphonates was 6.7% compared to 48.4% in patients not treated with adjuvant systemic bisphosphonates (p < 0.0001). In patients with both resectable and unresectable primary aggressive, recurrent, or metastatic GCT disease, systemic bisphosphonate and denosumab demonstrated good efficacy with decreased rates of disease progression and recurrence. In general the side effects of bisphosphonates were mild while denosuCorresponding author.