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 denosumab had a more severe side
effect profile. Conclusions: Systemic treatment with bisphosphonates or
denosumab in cases of GCT is promising, but there is a lack of high-level
evidence with sufficient follow-up supporting their use. We believe the current
literature provides moderate support to recommend a short course of adjuvant
peri-operative systemic bisphosphonate treatment for patients with resectable
primary GCT and moderate support to recommend adjuvant peri-operative
(resectable) and non-operative (unresectable) use of denosumab in cases of
primary aggressive, recurrent, or metastatic GCT. With either systemic
treatment, patients should be well counseled on all potential side effects in
addition to alternative treatment, which includes the option of no systemic
treatment.