Simple SummaryThere is limited evidence in the current literature about the best management of the recurrent giant cell tumor of bones (GCTB). The aim of this systematic review is to summarize and analyze the contemporary treatment modalities of recurrent GCTB and evaluate their impact on second recurrence rate and function. Based on our findings, the combination of intralesional curettage and cavity filling with polymethylmethacrylate cement yields the best results and outcomes.AbstractThe giant cell tumor of bones (GCTB) is a benign bone tumor with high postoperative recurrence potential. No specific treatment protocol has been developed to date in case of tumor recurrence, and the kind of re-operative surgery depends upon the surgeon’s preferences. The aim of this systematic review is to determine the second recurrence rate and the respective functional results of the available treatment options applied to recurrent GCTB. Medline/PubMed and Scopus were searched to identify articles published until March 2023. Twelve studies fulfilled the inclusion criteria, comprising 458 patients suffering from recurrent GCTB. The overall incidence of second recurrence was 20.5%, at a mean interval of 28.8 months after the first surgery, and it was more evident after intralesional curettage (IC) surgery than en-bloc resection (EBR) (p= 0.012). In the IC group of patients, the second recurrence rate was lower and the functional outcome was greater when polymethylmethacrylate cement (PMMAc) was used as an adjuvant instead of bone grafting (p< 0.001 for both parameters). Reconstruction of the created bone defect after EBR with a structural allograft provided a better outcome than prosthesis (p= 0.028). According to this systematic review, EBR (first choice) and IC with PMMAc (second choice) are the best treatment options for recurrent GCTB.