Clinical outcome of recurrent giant cell tumor of the extremity in the era before molecular target therapy: the Japanese Musculoskeletal Oncology Group study

BACKGROUND: Giant cell tumor of the bone (GCTB) is classified as an intermediate, locally aggressive but rarely metastasizing tumor. The mainstay of treatment for the treatment of GCTB had been the surgical removal until an anti- receptor activator of nuclear factor-kappa B ligands (RANKL) antibody denosumab was developed. And favorable responses and the possibility of surgical downstaging have been reported. However, the long-term outcome of denosumab has not yet been confirmed and moreover the long-term clinical outcome after the recurrence of GCTB in the era before molecular target therapy is still uncertain. The aim of this study was to evaluate the long-term clinical outcome of recurrent GCTB of the extremity in the era before molecular target therapy and to determine the factors that affect the repetitive recurrence and sacrifice of adjacent joints. METHODS: This multicenter study focused only recurrent GCTB of the extremity with no medical treatment and included 103 patients treated from 1980 to 2008. RESULTS: Thirty-two (31.1 %) patients developed repetitive recurrences after salvage surgery. Second curettage and venue of initial surgery (non-cancer hospital) were both significantly correlated with repetitive recurrence in univariate (P = 0.034 and P = 0.002) and multivariate (P = 0.004 and P = 0.001) analyses. Seventy-two (76.6 %) of 94 patients achieved successful preservation of adjacent joints. Campanacci Grade III was significantly correlated with sacrifice of the adjacent joint by univariate statistical analysis (P = 0.019), although its impact was only marginally significant by multivariate analysis (P = 0.059). Seventeen patients (16.5 %) developed distant metastasis, and one patient (0.97 %) developed malignant transformation. Finally, 94/103 patients (91.3 %) with recurrent GCTB were successfully rendered NED by further surgical treatment. CONCLUSIONS: We concluded that repetitive, thorough curettage with surgical adjuvant treatment resulted in a favorable rate of adjacent joint preservation (76.6 %), but recurettage inferred a risk of repetitive recurrences. Although the treatment strategy against the recurrent GCTB is being updated with denosumab, we believe that our data will be useful for future comparisons with the long-term clinical benefit of denosumab.