Does initial surgical treatment influence the management of recurrent giant cell tumor of bone?

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Berk KIRAN, Sercan BAHADIR, Berkay DOĞAN, Berksu POLAT, Osman Emre AYCAN This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7879093/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: The optimal management of recurrent giant cell tumor of bone (GCTB) remains controversial, particularly regarding the choice between repeat intralesional surgery and wide resection. This study aimed to analyze the effects of tumor localization, demographic factors, and surgical strategies on secondary recurrence in patients treated for recurrent GCTB. Methods: A retrospective review was conducted on 45 patients surgically treated for recurrent GCTB between 2005 and 2020. Thirteen patients were excluded due to insufficient follow-up or incomplete radiological data, leaving 32 patients eligible for analysis. Data regarding patient demographics, tumor characteristics, primary treatment center, surgical method for recurrence, neoadjuvant denosumab use, and oncologic outcomes were collected. Recurrence-free survival (RFS) was evaluated using Kaplan–Meier analysis, and factors affecting secondary recurrence were assessed using univariate statistics. Results: The mean age at recurrence surgery was 32.7 ± 9.7 years, with a mean follow-up of 87.5 months. Secondary recurrence occurred in 11 patients (34.4%) at a mean interval of 23.8 months. The secondary recurrence rate was higher in the repeat intralesional curettage group (38%) compared with the wide resection group (16%). Extracompartmental extension was significantly associated with recurrence (36% vs. 23%). Secondary recurrence developed in 28% of patients who received neoadjuvant denosumab and in 36% of those who did not. Pulmonary metastases occurred in 15.6% of cases. The 2-year and 5-year RFS rates were 84% and 72%, respectively, and the mean MSTS functional score was 25.6 (85.3%). Conclusion: Wide resection offers superior local control in recurrent GCTB compared with repeat curettage; however, extended curettage with adjuvants remains a viable joint-preserving option in selected cases. Extracompartmental extension and distal radius localization were associated with an increased risk of re-recurrence. Initial treatment quality and surgeon experience appear to influence oncologic outcomes, supporting early referral to specialized musculoskeletal oncology centers. Long-term follow-up is essential due to the risk of recurrence and pulmonary metastasis. Giant cell tumor of bone recurrence intralesional curettage wide resection denosumab musculoskeletal oncology Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Giant cell tumors (GCT) of the bone are benign but locally aggressive neoplasms that account for approximately 5% of all primary bone tumors and about 20% of benign skeletal lesions [ 1 – 3 ]. It typically affects skeletally mature young adults, peaking in the third and fourth decades of life, with a slight female predominance [ 1 ]. The most common anatomical sites are the distal femur, proximal tibia, and distal radius, where tumors characteristically involve the epiphyseal–metaphyseal region of long bones [ 3 ]. The distal radius, in particular, has been associated with a higher recurrence risk due to its anatomical constraints and difficulty in achieving adequate resection margins [ 2 , 3 ]. Although GCT of bone is classified as benign, it shows unpredictable biological behavior, with pulmonary metastasis reported in 1–9% of patients and malignant transformation in 1–3% of patients [ 3 , 4 ]. The primary challenge in managing GCT is its tendency for local recurrence, especially after intralesional curettage [ 1 – 7 ]. Reported recurrence rates after curettage range from 10% to 65%, depending on tumor aggressiveness and the use of adjuvant therapies [ 3 – 5 , 7 , 8 ]. Approximately 70% of recurrences occur within the first two years after the initial surgery [ 9 ]. Furthermore, local recurrence is associated with an increased risk of pulmonary metastasis, emphasizing the need for careful oncologic control [ 10 ]. Therefore, the optimal surgical strategy remains controversial: while intralesional curettage preserves function, it carries a higher recurrence risk; in contrast, wide resection lowers recurrence to 2–13% but results in greater morbidity and functional impairment [ 4 , 5 , 9 ]. Management becomes even more challenging in patients with recurrent GCT. Treatment options include repeat curettage or wide resection; however, the ideal approach remains debatable [ 3 – 9 ]. Studies have shown that repeat curettage combined with adjuvants, such as high-speed burring and polymethylmethacrylate (PMMA), yields acceptable control rates [ 1 – 4 , 9 ]. One study reported a re-recurrence rate of 58.8% when no adjuvants were used, which decreased to 21.7% when a high-speed burr and PMMA were used [ 4 , 9 , 11 ]. In contrast, wide resection has been shown to nearly eliminate recurrence in selected cases but may necessitate complex reconstruction or endoprosthesis in up to 21% of patients [ 3 – 5 , 7 , 9 ]. However, limited data exist regarding the clinicopathological or treatment-related factors that most influence recurrent tumor behavior and outcomes. This study aimed to evaluate the impact of tumor localization, demographic characteristics, and surgical treatment methods on the development of secondary recurrence in patients treated for recurrent GCT of the bone at our institution. Patients and Methods Between January 2005 and December 2020, 45 patients who underwent surgery for recurrent giant cell tumor of bone (GCTB) were identified from the institutional tumor registry of our tertiary musculoskeletal oncology center. Patients were eligible for inclusion if they had histologically confirmed recurrent GCTB of the extremities and a minimum clinical and radiological follow-up of 24 months after surgery for recurrence. Patients were excluded if they had insufficient follow-up, incomplete medical or radiological records, or a follow-up period of < 24 months. Ultimately, 32 patients fulfilled the inclusion criteria and were included in the final analysis (Fig. 1 ). This retrospective cohort study was approved by the Institutional Review Board and conducted in accordance with the principles of the Declaration of Helsinki. The collected data included demographic variables (age and sex), tumor-related characteristics (anatomical site, Campanacci grade, intra- vs. extracompartmental extension, and presence of pathological fracture), and treatment details. The primary treatment center was also recorded, and patients were grouped according to whether they received their initial treatment at our institution or at an outside facility. The treatment-related factors analyzed included the surgical method used for recurrent disease (intralesional curettage ± adjuvants vs. wide resection and reconstruction) and the administration of neoadjuvant denosumab. Intralesional surgery was performed using curettage and a high-speed burr. Chemical (phenol) or thermal cauterization, with or without cryotherapy, was used as an adjuvant treatment in selected cases. The resulting defect was filled with polymethylmethacrylate (PMMA) or a structural allograft when necessary. Wide en bloc resection was preferred in patients with cortical breach, extracompartmental soft-tissue extension, or recurrence following previous curettage. Reconstructions following resection included osteoarticular allografts, autografts, or modular endoprostheses, depending on the tumor site and bone stock. Neoadjuvant denosumab (120 mg subcutaneously every 4 weeks, with additional loading doses on days 8 and 15) was administered in selected cases of advanced, borderline resectable, or technically challenging recurrent tumors to facilitate surgery. The primary outcome of this study was the incidence of secondary local recurrence following treatment for recurrent GCTB. Secondary outcomes included recurrence-free survival (RFS), development of pulmonary metastasis, surgical complications (classified using the Henderson system), and functional outcomes assessed using the Musculoskeletal Tumor Society (MSTS) scoring system at the final follow-up. Categorical variables are expressed as frequencies and percentages, and continuous data are expressed as mean ± standard deviation (SD) or median with range based on distribution. Comparisons between treatment groups (intralesional vs. wide resection; denosumab vs. no denosumab) were made using the chi-square or Fisher’s exact test for categorical variables and the Student’s t-test or Mann–Whitney U test for continuous variables. Kaplan–Meier survival analysis was performed to estimate RFS, and the log-rank test was used to compare the survival curves. Cox proportional hazards regression analysis was used to evaluate the independent risk factors for secondary recurrence. Statistical significance was set at p < 0.05. Results A total of 32 patients with recurrent giant cell tumors of the bone (GCTB) were included in the study. The mean age at the time of surgery for recurrence was 32.7 ± 9.7 years, and the mean follow-up period was 87.5 months (range, 24–156 months) (Table 1 ). The distal radius was the most frequent tumor site, followed by the proximal tibia and the distal femur. The most commonly applied primary treatment method was intralesional curettage with high-speed burring, phenol application, and polymethylmethacrylate (PMMA) filling. Table 1 Patient demographics and tumor characteristics Variable Value Patients, n 32 Age, mean ± SD (years) 32.7 ± 9.7 Follow-up, mean (range), months 87.5 (24–156) Involvement Distal radius 11 (34.4%) Proximal tibia 7 (21.9%) Distal femur 6 (18.8%) Other 8 (25.0%) Most common primary treatment Intralesional curettage + High-speed burr + Phenol + PMMA Of the 32 patients, 11 (34%) had undergone primary surgery at an elsewhere institution. Due to the lack of operative details and inconsistent surgical documentation from these centers, recurrence patterns in this subgroup could not be fully assessed. In contrast, patients who received their initial treatment at our institution were managed using standardized surgical techniques and follow-up protocols, allowing for a more accurate evaluation of treatment outcomes (Fig. 2 ). The overall recurrence rate after primary intralesional surgery at our institution was 17%. Following surgery for recurrent disease, secondary recurrence developed in 11 patients (34.4%), with a mean time to recurrence of 23.8 months. The rate of secondary recurrence was 38% among patients treated with repeat intralesional curettage compared with 16% among those treated with wide resection (Fig. 3 ). No recurrence was observed in the single patient who underwent amputation (Table 2 ). Table 2 Outcomes after surgery for recurrent GCTB Treatment for recurrence n Secondary recurrence, n (%) Intralesional 24 9 (38%) Wide resection 6 1 (16%) Arthrodesis 1 1 (100%) Amputation 1 0 (0%) Seven patients received neoadjuvant denosumab therapy for recurrent diseases. Secondary recurrence occurred in 28% (n = 2) of patients who received denosumab and 36% (n = 9) of patients who did not receive denosumab (Table 3 ). Extracompartmental tumor involvement at presentation was associated with a significantly higher risk of secondary recurrence than intracompartmental disease (36% vs. 23%). Table 3 Denosumab and compartmental status Variable Group Secondary recurrence (%) Denosumab Yes (n = 7) 28% No (n = 25) 36% Compartmental status Extracompartmental 36% Intracompartmental 23% Pulmonary metastases developed in five patients (15.6%). The incidence was 11% in patients treated with intralesional surgery and 16% in those treated with a wide resection. These metastases were more frequently observed in patients with aggressive tumor features and recurrent diseases. Histopathological review confirmed that all wide resection procedures achieved surgical margins greater than 5 mm. Functional outcomes at the final follow-up were satisfactory, with a mean Musculoskeletal Tumor Society (MSTS) score of 25.6, corresponding to 85.3% of normal limb function. Kaplan–Meier analysis demonstrated a recurrence-free survival (RFS) rate of 84% at 2 years and 72% at 5 years (Fig. 4 ). Discussion The results of this study underscore the therapeutic challenges in managing recurrent giant cell tumors of the bone (GCTB), highlighting the critical balance between achieving local oncologic control and preserving limb function [ 1 ]. Our findings contribute to the ongoing debate regarding the optimal surgical approach for challenging cases. One of the most striking findings of our study is that wide resection for recurrent GCTB substantially lowered the rate of secondary recurrence compared to repeat intralesional curettage (16% vs. 38%). This aligns with prior studies emphasizing the superior local control afforded by tumor resection [ 2 , 3 ]. (Table 4 ) Several large series have reported recurrence rates as low as 5% following resection [ 4 ], and Tsukamoto et al. noted no re-recurrence in some cohorts after en bloc resection [ 5 ]. Nevertheless, wide resection is associated with greater complications and functional losses. Thus, despite the higher re-recurrence rate, repeat curettage remains a clinically attractive joint-preserving option when functional outcomes are prioritized. In our cohort, seven of eleven patients with secondary recurrence underwent repeat curettage, underscoring its continued preference despite its limitations. Table 4 Comparison of recurrence rates in recurrent GCTB across published series Study (Year) Follow-up (mo) No. of patients Surgical method Recurrence rate Tunn (2008) 63 19 Wide resection 6% Curettage ± PMMA ± Phenol 36% Balke (2009) 77 66 Wide resection 0% Curettage only 67% Curettage + PMMA 36% Curettage + HS burr + PMMA 22% Prosser (2005) 70 26 Wide resection 0% Curettage + HS burr 21% Turcotte (2002) 60 23 Curettage ± HS burr ± PMMA ± Phenol 35% Klenke (2010) 134 46 Wide resection 6% Curettage + HS burr + Phenol 50% Curettage + HS burr + PMMA + Phenol 14% This study (2024) 87 32 Wide resection 16% Curettage + HS burr + PMMA + Phenol 38% Our results also identified extracompartmental (soft tissue) involvement as a significant adverse prognostic factor, with a higher recurrence rate than intracompartmental tumors (36% vs. 23%). This is consistent with the findings of Klenke et al., who highlighted extracompartmental extension as an independent predictor of recurrence [ 7 ]. Campanacci grade 3 lesions, often characterized by cortical breach and soft-tissue invasion, similarly demonstrate aggressive behavior and worse outcomes, for which en bloc resection is often advocated [ 5 , 7 ]. The distal radius emerged as the most common site of recurrence in our cohort, corroborating previous reports that this location poses one of the greatest management challenges [ 2 , 3 , 10 ]. The dilemma lies in securing oncologic control and maintaining wrist function. Meta-analyses have confirmed that curettage in distal radius GCTs carries significantly higher recurrence rates compared with resection, but the latter frequently compromises function [ 12 – 14 ]. Our findings parallel these results, demonstrating both the anatomical challenges and the need for individualized surgical planning at this high-risk site. The role of surgical adjuvants deserves further emphasis. High-speed burring and PMMA filling were standard in our cohort and are widely supported in the literature for reducing the risk of recurrence [ 2 , 4 ]. While adjuvants clearly improve outcomes, our repeat curettage group still showed a 38% re-recurrence rate, suggesting that tumor biology and prior treatments strongly influence prognosis in recurrent cases. The impact of denosumab on local control remains unclear. In our study, secondary recurrence occurred in 28% of denosumab-treated patients and 36% of patients who did not receive denosumab. Lipplaa et al. summarized the dual nature of denosumab: it facilitates surgery by reducing tumor size and inducing sclerosis, but it may also obscure margins and increase the risk of residual disease [ 6 ]. Our results mirror these concerns, showing no definitive benefit of denosumab in recurrent settings. Therefore, its role in preventing re-recurrence requires further evaluation in prospective multicenter studies. Pulmonary metastases were observed in 15.6% of patients, which is higher than the 1–9% reported for primary GCTB [ 10 ]. This finding is consistent with prior evidence that recurrent disease is a strong risk factor for metastasis [ 10 ]. Importantly, most pulmonary metastases behave indolently and can be managed successfully with surgery, and no disease-related deaths were observed in our cohort. These findings highlight the need for careful long-term surveillance of patients with recurrent GCTB. Despite the oncological challenges, the functional outcomes remained favorable, with a mean MSTS score of 25.6 (85.3%). Similar series have reported good to excellent function after both intralesional and resection procedures, particularly in distal radius reconstructions [ 13 – 14 ]. Our results confirm that even after repeated surgeries, satisfactory function can be preserved in most patients. A significant limitation of the present study is the inherent selection bias attributable to its status as a tertiary referral center. A substantial portion of the patient cohort received initial treatment at outside institutions, often by surgeons not specifically trained in orthopedic oncology, before being referred to our center for the treatment of recurrent disease. This scenario is well documented in the literature; one source noted that 20 of 22 patients with recurrent GCT had been initially treated by general orthopedic surgeons elsewhere[ 1 ], while another reported that 54% of its cohort had undergone prior surgery at other facilities [ 2 ]. This presents a substantial confounding factor when interpreting oncologic outcomes because the quality and specifics of the primary intervention are often unknown. As one source explicitly states, it is frequently unclear whether a subsequent presentation represents a true recurrence after an adequate procedure or is simply the progression of residual macroscopic tumor left after incomplete initial curettage[ 2 ]. This underscores the principle that the primary management of these tumors by non-specialists can have a "major impact on the recurrence rate", and that early referral to a specialized treatment center is advised to "avoid errors, complications, and poor outcomes"[ 3 ]. Therefore, the recurrence rates observed in our cohort may reflect not only the efficacy of our reoperative techniques but also the sequelae of the initial undocumented treatment performed at outside institutions. This study had several limitations. Its retrospective design and relatively small sample size limit its statistical power. Approximately one-third of patients underwent primary surgery at institutions other than ours, often by non-oncologic surgeons, which may have influenced the biological behavior of the recurrences [ 3 ]. In addition, the small number of patients receiving denosumab limits the conclusions regarding its efficacy. In conclusion, wide resection provides superior local control in recurrent GCTB, whereas repeat curettage, especially with adjuvants, remains a valuable joint-preserving alternative. Extracompartmental involvement and distal radius localization signify a higher recurrence risk and should guide surgical decision-making. Denosumab can facilitate surgery but does not appear to reduce recurrence in this setting. Pulmonary metastases are not uncommon in recurrent cases and require careful surveillance. Overall, the functional outcomes remained good, underscoring that with careful case selection, limb-sparing approaches can still achieve acceptable results in recurrent GCTB. Declarations Conflict of interest: The authors declare that they have no conflict of interest. Ethics approval: This study was approved by the Institutional Review Board/Ethics Committee (Approval No: 29/204, Date: 02.12.2024). All procedures were conducted in accordance with the ethical standards of the Declaration of Helsinki. Informed consent: Written informed consent was obtained from all participants included in the study. Additional informed consent was obtained for the publication of clinical images. Funding: The authors received no financial support for the research, authorship, and/or publication of this article. Author Contribution E.A. conceived and designed the study, performed the statistical analysis, and wrote the main manuscript. B.Y. and S.K. contributed to patient data collection and manuscript preparation. B.A. and B.S. contributed to data acquisition, verification of clinical records, and critical manuscript revision. All authors reviewed and approved the final version of the manuscript. Data Availability The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. References Behera KC, Singla M, Yadav U et al (2022) A tertiary care centre experience of recurrent giant cell tumor around the knee joint. Cureus 14(9):e29788. 10.7759/cureus.29788 Panchwagh Y, Puri A, Agarwal M, Anchan C, Shah M (2007) Giant cell tumor of distal end radius: Do we know the answer? Indian J Orthop 41(2):139–145. 10.4103/0019-5413.32046 Greenberg DD (2025) Giant cell tumor of bone. In: Biermann JS, Siegel GW, editors. Orthopaedic Knowledge Update: Musculoskeletal Tumors. 5th ed. Rosemont (IL): American Academy of Orthopaedic Surgeons; pp. 179–92. ISBN: 978-1-9752-2595-7 / 978-1-9752-2597-1). Balke M, Ahrens H, Streitbuerger A et al (2009) Treatment options for recurrent giant cell tumors of bone. J Cancer Res Clin Oncol 135(1):149–158. 10.1007/s00432-008-0427-x Tsukamoto S, Mavrogenis AF, Hindiskere S et al (2022) Outcome of reoperation for local recurrence following en bloc resection for giant cell tumor of bone of the extremity. Curr Oncol 29(9):6383–6399. 10.3390/curroncol29090503 Lipplaa A, Dijkstra S, Gelderblom H (2019) Challenges of denosumab in giant cell tumor of bone and other giant cell-rich tumors of bone. Curr Opin Oncol 31(4):329–335. 10.1097/CCO.0000000000000529 Klenke FM, Wenger DE, Inwards CY, Rose PS, Sim FH (2011) Giant cell tumor of bone: Risk factors for recurrence. Clin Orthop Relat Res 469(2):591–599. 10.1007/s11999-010-1501-7 Teixeira LEM, Vilela JCS, Miranda RH, Gomes AH, Costa FA, de Faria VC (2014) Giant cell tumors of bone: Nonsurgical factors associated with local recurrence. Acta Orthop Traumatol Turc 48(2):136–140. 10.3944/AOTT.2014.2714 Errani C, Tsukamoto S, Leone G et al (2017) Higher local recurrence rates after intralesional surgery for giant cell tumor of the proximal femur compared to other sites. Eur J Orthop Surg Traumatol 27(6):813–819. 10.1007/s00590-017-1983-z Viswanathan S, Jambhekar NA (2010) Metastatic giant cell tumor of bone: Are there associated factors and best treatment modalities? Clin Orthop Relat Res 468(3):827–833. 10.1007/s11999-009-0966-8 Algawahmed H, Turcotte R, Farrokhyar F, Ghert M (2010) High-speed burring with and without the use of surgical adjuvants in the intralesional management of giant cell tumor of bone: A systematic review and meta-analysis. Sarcoma 2010:586090. 10.1155/2010/586090 Liu YP, Li KH, Sun BH (2012) Which treatment is the best for giant cell tumors of the distal radius? A meta-analysis. Clin Orthop Relat Res 470(10):2886–2894. 10.1007/s11999-012-2464-7 Zou C, Lin T, Wang B et al (2019) Management of giant cell tumor within the distal radius: A retrospective study of 58 cases from a single center. J Bone Oncol 14:100211. 10.1016/j.jbo.2018.100211 Koucheki R, Gazendam A, Perera J et al (2023) Management of giant cell tumors of the distal radius: A systematic review and meta-analysis. Eur J Orthop Surg Traumatol 33(4):759–772. 10.1007/s00590-022-03252-9 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7879093","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":535632738,"identity":"b8e92365-2302-465a-808c-d68357fa7550","order_by":0,"name":"Berk KIRAN","email":"","orcid":"","institution":"Baltalimanı Bone Diseases Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Berk","middleName":"","lastName":"KIRAN","suffix":""},{"id":535632739,"identity":"69c3ff1e-4a97-4f57-a08f-1af3ebf33094","order_by":1,"name":"Sercan BAHADIR","email":"","orcid":"","institution":"Baltalimanı Bone Diseases Training and 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15:52:31","extension":"xml","order_by":33,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":63323,"visible":true,"origin":"","legend":"","description":"","filename":"3c7dc344f5584b76a44b7a6e86cf0f771structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7879093/v1/993c5ccc18be5d6d61732b50.xml"},{"id":95276918,"identity":"4ebab478-97b9-4b5e-a977-2ecdbb8d3989","added_by":"auto","created_at":"2025-11-06 08:32:32","extension":"html","order_by":34,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":70871,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7879093/v1/dcc214166506da8035a9332d.html"},{"id":95313910,"identity":"bff7b63f-79bd-47d6-8630-a5273e649d72","added_by":"auto","created_at":"2025-11-06 15:52:14","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":134232,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart demonstrating the patient selection process and inclusion criteria for the study.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7879093/v1/c83ca185393927e84690004f.jpg"},{"id":95276885,"identity":"86c3d60e-1b44-445e-aead-552c50097d76","added_by":"auto","created_at":"2025-11-06 08:32:31","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":234315,"visible":true,"origin":"","legend":"\u003cp\u003e(a–d): Recurrent giant cell tumor of the left distal femur in a 32-year-old female previously treated at our institution with curettage, PMMA cementation, and plate fixation (a). At 38 months postoperatively, follow-up radiographs revealed a new osteolytic lesion proximal to the cement mantle at the posterolateral cortex (b). Sagittal, coronal, and axial MRI images confirmed a contained posterolateral recurrence without extraosseous extension (c). The patient was treated with repeat extended curettage and PMMA filling while retaining stable fixation, with no recurrence at 36 months follow-up (d).\u003c/p\u003e","description":"","filename":"Figure2a.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7879093/v1/62695f5c913cfa5b3f86a602.jpg"},{"id":95276887,"identity":"489f441f-f1bb-45ce-b759-d8ab5dceba89","added_by":"auto","created_at":"2025-11-06 08:32:31","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":257637,"visible":true,"origin":"","legend":"\u003cp\u003e(a–d): Recurrent giant cell tumor of the right proximal tibia in a 38-year-old male previously treated at an elsewhere center with curettage and PMMA. Preoperative radiographs (a) and CT scan (b) demonstrate cortical expansion and osteolytic destruction around the cement mantle in the proximal metaphysis. Coronal T1- and T2-weighted MRI images and axial T1 series (c) show intramedullary extension and cortical thinning consistent with aggressive recurrence. Following wide resection, reconstruction was performed using a proximal tibial modular tumor endoprosthesis with no recurrence at 27 months follow-up (d).\u003c/p\u003e","description":"","filename":"Figure3a.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7879093/v1/80b66e8ce2f694d7cc162d94.jpg"},{"id":95276891,"identity":"f4d3ace5-b979-4492-b0ca-5c99a33a1306","added_by":"auto","created_at":"2025-11-06 08:32:31","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":136535,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier survival analysis demonstrated a recurrence-free survival (RFS) rate of 84% at 2 years and 72% at 5 years\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7879093/v1/e87be3f4209788503c18a9f4.jpg"},{"id":99321095,"identity":"82609a2f-837c-4186-93db-86bb7254149a","added_by":"auto","created_at":"2025-12-31 16:39:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1291108,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7879093/v1/f6c89b99-f5f9-40d5-acc4-84bf74a16327.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Does initial surgical treatment influence the management of recurrent giant cell tumor of bone?","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGiant cell tumors (GCT) of the bone are benign but locally aggressive neoplasms that account for approximately 5% of all primary bone tumors and about 20% of benign skeletal lesions [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. It typically affects skeletally mature young adults, peaking in the third and fourth decades of life, with a slight female predominance [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The most common anatomical sites are the distal femur, proximal tibia, and distal radius, where tumors characteristically involve the epiphyseal\u0026ndash;metaphyseal region of long bones [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The distal radius, in particular, has been associated with a higher recurrence risk due to its anatomical constraints and difficulty in achieving adequate resection margins [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Although GCT of bone is classified as benign, it shows unpredictable biological behavior, with pulmonary metastasis reported in 1\u0026ndash;9% of patients and malignant transformation in 1\u0026ndash;3% of patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe primary challenge in managing GCT is its tendency for local recurrence, especially after intralesional curettage [\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Reported recurrence rates after curettage range from 10% to 65%, depending on tumor aggressiveness and the use of adjuvant therapies [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Approximately 70% of recurrences occur within the first two years after the initial surgery [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Furthermore, local recurrence is associated with an increased risk of pulmonary metastasis, emphasizing the need for careful oncologic control [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Therefore, the optimal surgical strategy remains controversial: while intralesional curettage preserves function, it carries a higher recurrence risk; in contrast, wide resection lowers recurrence to 2\u0026ndash;13% but results in greater morbidity and functional impairment [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eManagement becomes even more challenging in patients with recurrent GCT. Treatment options include repeat curettage or wide resection; however, the ideal approach remains debatable [\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Studies have shown that repeat curettage combined with adjuvants, such as high-speed burring and polymethylmethacrylate (PMMA), yields acceptable control rates [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. One study reported a re-recurrence rate of 58.8% when no adjuvants were used, which decreased to 21.7% when a high-speed burr and PMMA were used [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In contrast, wide resection has been shown to nearly eliminate recurrence in selected cases but may necessitate complex reconstruction or endoprosthesis in up to 21% of patients [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, limited data exist regarding the clinicopathological or treatment-related factors that most influence recurrent tumor behavior and outcomes.\u003c/p\u003e\u003cp\u003e This study aimed to evaluate the impact of tumor localization, demographic characteristics, and surgical treatment methods on the development of secondary recurrence in patients treated for recurrent GCT of the bone at our institution.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cp\u003eBetween January 2005 and December 2020, 45 patients who underwent surgery for recurrent giant cell tumor of bone (GCTB) were identified from the institutional tumor registry of our tertiary musculoskeletal oncology center. Patients were eligible for inclusion if they had histologically confirmed recurrent GCTB of the extremities and a minimum clinical and radiological follow-up of 24 months after surgery for recurrence. Patients were excluded if they had insufficient follow-up, incomplete medical or radiological records, or a follow-up period of \u0026lt;\u0026thinsp;24 months. Ultimately, 32 patients fulfilled the inclusion criteria and were included in the final analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e This retrospective cohort study was approved by the Institutional Review Board and conducted in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e\u003cp\u003eThe collected data included demographic variables (age and sex), tumor-related characteristics (anatomical site, Campanacci grade, intra- vs. extracompartmental extension, and presence of pathological fracture), and treatment details. The primary treatment center was also recorded, and patients were grouped according to whether they received their initial treatment at our institution or at an outside facility. The treatment-related factors analyzed included the surgical method used for recurrent disease (intralesional curettage\u0026thinsp;\u0026plusmn;\u0026thinsp;adjuvants vs. wide resection and reconstruction) and the administration of neoadjuvant denosumab.\u003c/p\u003e\u003cp\u003eIntralesional surgery was performed using curettage and a high-speed burr. Chemical (phenol) or thermal cauterization, with or without cryotherapy, was used as an adjuvant treatment in selected cases. The resulting defect was filled with polymethylmethacrylate (PMMA) or a structural allograft when necessary. Wide en bloc resection was preferred in patients with cortical breach, extracompartmental soft-tissue extension, or recurrence following previous curettage. Reconstructions following resection included osteoarticular allografts, autografts, or modular endoprostheses, depending on the tumor site and bone stock. Neoadjuvant denosumab (120 mg subcutaneously every 4 weeks, with additional loading doses on days 8 and 15) was administered in selected cases of advanced, borderline resectable, or technically challenging recurrent tumors to facilitate surgery.\u003c/p\u003e\u003cp\u003eThe primary outcome of this study was the incidence of secondary local recurrence following treatment for recurrent GCTB. Secondary outcomes included recurrence-free survival (RFS), development of pulmonary metastasis, surgical complications (classified using the Henderson system), and functional outcomes assessed using the Musculoskeletal Tumor Society (MSTS) scoring system at the final follow-up.\u003c/p\u003e\u003cp\u003eCategorical variables are expressed as frequencies and percentages, and continuous data are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or median with range based on distribution. Comparisons between treatment groups (intralesional vs. wide resection; denosumab vs. no denosumab) were made using the chi-square or Fisher\u0026rsquo;s exact test for categorical variables and the Student\u0026rsquo;s t-test or Mann\u0026ndash;Whitney U test for continuous variables. Kaplan\u0026ndash;Meier survival analysis was performed to estimate RFS, and the log-rank test was used to compare the survival curves. Cox proportional hazards regression analysis was used to evaluate the independent risk factors for secondary recurrence. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 32 patients with recurrent giant cell tumors of the bone (GCTB) were included in the study. The mean age at the time of surgery for recurrence was 32.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7 years, and the mean follow-up period was 87.5 months (range, 24\u0026ndash;156 months) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The distal radius was the most frequent tumor site, followed by the proximal tibia and the distal femur. The most commonly applied primary treatment method was intralesional curettage with high-speed burring, phenol application, and polymethylmethacrylate (PMMA) filling.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePatient demographics and tumor characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eValue\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatients, n\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFollow-up, mean (range), months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e87.5 (24\u0026ndash;156)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvolvement\u003c/p\u003e\u003cp\u003eDistal radius\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (34.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProximal tibia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (21.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDistal femur\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (18.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (25.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMost common primary treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIntralesional curettage\u0026thinsp;+\u0026thinsp;High-speed burr\u0026thinsp;+\u0026thinsp;Phenol\u0026thinsp;+\u0026thinsp;PMMA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eOf the 32 patients, 11 (34%) had undergone primary surgery at an elsewhere institution. Due to the lack of operative details and inconsistent surgical documentation from these centers, recurrence patterns in this subgroup could not be fully assessed. In contrast, patients who received their initial treatment at our institution were managed using standardized surgical techniques and follow-up protocols, allowing for a more accurate evaluation of treatment outcomes (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe overall recurrence rate after primary intralesional surgery at our institution was 17%. Following surgery for recurrent disease, secondary recurrence developed in 11 patients (34.4%), with a mean time to recurrence of 23.8 months. The rate of secondary recurrence was 38% among patients treated with repeat intralesional curettage compared with 16% among those treated with wide resection (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). No recurrence was observed in the single patient who underwent amputation (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eOutcomes after surgery for recurrent GCTB\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreatment for recurrence\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003en\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSecondary recurrence, n (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntralesional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (38%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWide resection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (16%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eArthrodesis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (100%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAmputation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eSeven patients received neoadjuvant denosumab therapy for recurrent diseases. Secondary recurrence occurred in 28% (n\u0026thinsp;=\u0026thinsp;2) of patients who received denosumab and 36% (n\u0026thinsp;=\u0026thinsp;9) of patients who did not receive denosumab (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Extracompartmental tumor involvement at presentation was associated with a significantly higher risk of secondary recurrence than intracompartmental disease (36% vs. 23%).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDenosumab and compartmental status\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSecondary recurrence (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDenosumab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes (n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo (n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCompartmental status\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eExtracompartmental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIntracompartmental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePulmonary metastases developed in five patients (15.6%). The incidence was 11% in patients treated with intralesional surgery and 16% in those treated with a wide resection. These metastases were more frequently observed in patients with aggressive tumor features and recurrent diseases.\u003c/p\u003e\u003cp\u003e Histopathological review confirmed that all wide resection procedures achieved surgical margins greater than 5 mm. Functional outcomes at the final follow-up were satisfactory, with a mean Musculoskeletal Tumor Society (MSTS) score of 25.6, corresponding to 85.3% of normal limb function.\u003c/p\u003e\u003cp\u003eKaplan\u0026ndash;Meier analysis demonstrated a recurrence-free survival (RFS) rate of 84% at 2 years and 72% at 5 years (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe results of this study underscore the therapeutic challenges in managing recurrent giant cell tumors of the bone (GCTB), highlighting the critical balance between achieving local oncologic control and preserving limb function [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Our findings contribute to the ongoing debate regarding the optimal surgical approach for challenging cases.\u003c/p\u003e\u003cp\u003eOne of the most striking findings of our study is that wide resection for recurrent GCTB substantially lowered the rate of secondary recurrence compared to repeat intralesional curettage (16% vs. 38%). This aligns with prior studies emphasizing the superior local control afforded by tumor resection [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) Several large series have reported recurrence rates as low as 5% following resection [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and Tsukamoto et al. noted no re-recurrence in some cohorts after en bloc resection [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Nevertheless, wide resection is associated with greater complications and functional losses. Thus, despite the higher re-recurrence rate, repeat curettage remains a clinically attractive joint-preserving option when functional outcomes are prioritized. In our cohort, seven of eleven patients with secondary recurrence underwent repeat curettage, underscoring its continued preference despite its limitations.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of recurrence rates in recurrent GCTB across published series\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy (Year)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFollow-up (mo)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo. of patients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSurgical method\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRecurrence rate\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTunn (2008)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWide resection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCurettage\u0026thinsp;\u0026plusmn;\u0026thinsp;PMMA\u0026thinsp;\u0026plusmn;\u0026thinsp;Phenol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e36%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBalke (2009)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWide resection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCurettage only\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e67%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCurettage\u0026thinsp;+\u0026thinsp;PMMA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e36%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCurettage\u0026thinsp;+\u0026thinsp;HS burr\u0026thinsp;+\u0026thinsp;PMMA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e22%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProsser (2005)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWide resection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCurettage\u0026thinsp;+\u0026thinsp;HS burr\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e21%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTurcotte (2002)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCurettage\u0026thinsp;\u0026plusmn;\u0026thinsp;HS burr\u0026thinsp;\u0026plusmn;\u0026thinsp;PMMA\u0026thinsp;\u0026plusmn;\u0026thinsp;Phenol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e35%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKlenke (2010)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e134\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWide resection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCurettage\u0026thinsp;+\u0026thinsp;HS burr\u0026thinsp;+\u0026thinsp;Phenol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e50%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCurettage\u0026thinsp;+\u0026thinsp;HS burr\u0026thinsp;+\u0026thinsp;PMMA\u0026thinsp;+\u0026thinsp;Phenol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThis study (2024)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWide resection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e16%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCurettage\u0026thinsp;+\u0026thinsp;HS burr\u0026thinsp;+\u0026thinsp;PMMA\u0026thinsp;+\u0026thinsp;Phenol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e38%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eOur results also identified extracompartmental (soft tissue) involvement as a significant adverse prognostic factor, with a higher recurrence rate than intracompartmental tumors (36% vs. 23%). This is consistent with the findings of Klenke et al., who highlighted extracompartmental extension as an independent predictor of recurrence [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Campanacci grade 3 lesions, often characterized by cortical breach and soft-tissue invasion, similarly demonstrate aggressive behavior and worse outcomes, for which en bloc resection is often advocated [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe distal radius emerged as the most common site of recurrence in our cohort, corroborating previous reports that this location poses one of the greatest management challenges [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The dilemma lies in securing oncologic control and maintaining wrist function. Meta-analyses have confirmed that curettage in distal radius GCTs carries significantly higher recurrence rates compared with resection, but the latter frequently compromises function [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Our findings parallel these results, demonstrating both the anatomical challenges and the need for individualized surgical planning at this high-risk site.\u003c/p\u003e\u003cp\u003eThe role of surgical adjuvants deserves further emphasis. High-speed burring and PMMA filling were standard in our cohort and are widely supported in the literature for reducing the risk of recurrence [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. While adjuvants clearly improve outcomes, our repeat curettage group still showed a 38% re-recurrence rate, suggesting that tumor biology and prior treatments strongly influence prognosis in recurrent cases.\u003c/p\u003e\u003cp\u003eThe impact of denosumab on local control remains unclear. In our study, secondary recurrence occurred in 28% of denosumab-treated patients and 36% of patients who did not receive denosumab. Lipplaa et al. summarized the dual nature of denosumab: it facilitates surgery by reducing tumor size and inducing sclerosis, but it may also obscure margins and increase the risk of residual disease [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Our results mirror these concerns, showing no definitive benefit of denosumab in recurrent settings. Therefore, its role in preventing re-recurrence requires further evaluation in prospective multicenter studies.\u003c/p\u003e\u003cp\u003ePulmonary metastases were observed in 15.6% of patients, which is higher than the 1\u0026ndash;9% reported for primary GCTB [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This finding is consistent with prior evidence that recurrent disease is a strong risk factor for metastasis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Importantly, most pulmonary metastases behave indolently and can be managed successfully with surgery, and no disease-related deaths were observed in our cohort. These findings highlight the need for careful long-term surveillance of patients with recurrent GCTB.\u003c/p\u003e\u003cp\u003eDespite the oncological challenges, the functional outcomes remained favorable, with a mean MSTS score of 25.6 (85.3%). Similar series have reported good to excellent function after both intralesional and resection procedures, particularly in distal radius reconstructions [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Our results confirm that even after repeated surgeries, satisfactory function can be preserved in most patients.\u003c/p\u003e\u003cp\u003eA significant limitation of the present study is the inherent selection bias attributable to its status as a tertiary referral center. A substantial portion of the patient cohort received initial treatment at outside institutions, often by surgeons not specifically trained in orthopedic oncology, before being referred to our center for the treatment of recurrent disease. This scenario is well documented in the literature; one source noted that 20 of 22 patients with recurrent GCT had been initially treated by general orthopedic surgeons elsewhere[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], while another reported that 54% of its cohort had undergone prior surgery at other facilities [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. This presents a substantial confounding factor when interpreting oncologic outcomes because the quality and specifics of the primary intervention are often unknown. As one source explicitly states, it is frequently unclear whether a subsequent presentation represents a true recurrence after an adequate procedure or is simply the progression of residual macroscopic tumor left after incomplete initial curettage[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. This underscores the principle that the primary management of these tumors by non-specialists can have a \"major impact on the recurrence rate\", and that early referral to a specialized treatment center is advised to \"avoid errors, complications, and poor outcomes\"[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Therefore, the recurrence rates observed in our cohort may reflect not only the efficacy of our reoperative techniques but also the sequelae of the initial undocumented treatment performed at outside institutions.\u003c/p\u003e\u003cp\u003eThis study had several limitations. Its retrospective design and relatively small sample size limit its statistical power. Approximately one-third of patients underwent primary surgery at institutions other than ours, often by non-oncologic surgeons, which may have influenced the biological behavior of the recurrences [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In addition, the small number of patients receiving denosumab limits the conclusions regarding its efficacy.\u003c/p\u003e\u003cp\u003eIn conclusion, wide resection provides superior local control in recurrent GCTB, whereas repeat curettage, especially with adjuvants, remains a valuable joint-preserving alternative. Extracompartmental involvement and distal radius localization signify a higher recurrence risk and should guide surgical decision-making. Denosumab can facilitate surgery but does not appear to reduce recurrence in this setting. Pulmonary metastases are not uncommon in recurrent cases and require careful surveillance. Overall, the functional outcomes remained good, underscoring that with careful case selection, limb-sparing approaches can still achieve acceptable results in recurrent GCTB.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eConflict of interest:\u003c/h2\u003e\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e\u003cp\u003e This study was approved by the Institutional Review Board/Ethics Committee (Approval No: 29/204, Date: 02.12.2024). All procedures were conducted in accordance with the ethical standards of the Declaration of Helsinki.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eInformed consent:\u003c/strong\u003e\u003cp\u003e Written informed consent was obtained from all participants included in the study. Additional informed consent was obtained for the publication of clinical images.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eThe authors received no financial support for the research, authorship, and/or publication of this article.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eE.A. conceived and designed the study, performed the statistical analysis, and wrote the main manuscript. B.Y. and S.K. contributed to patient data collection and manuscript preparation. B.A. and B.S. contributed to data acquisition, verification of clinical records, and critical manuscript revision. All authors reviewed and approved the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBehera KC, Singla M, Yadav U et al (2022) A tertiary care centre experience of recurrent giant cell tumor around the knee joint. Cureus 14(9):e29788. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/cureus.29788\u003c/span\u003e\u003cspan address=\"10.7759/cureus.29788\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePanchwagh Y, Puri A, Agarwal M, Anchan C, Shah M (2007) Giant cell tumor of distal end radius: Do we know the answer? Indian J Orthop 41(2):139\u0026ndash;145. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/0019-5413.32046\u003c/span\u003e\u003cspan address=\"10.4103/0019-5413.32046\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGreenberg DD (2025) Giant cell tumor of bone. In: Biermann JS, Siegel GW, editors. Orthopaedic Knowledge Update: Musculoskeletal Tumors. 5th ed. Rosemont (IL): American Academy of Orthopaedic Surgeons; pp. 179\u0026ndash;92. \u003cem\u003eISBN: 978-1-9752-2595-7 / 978-1-9752-2597-1).\u003c/em\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBalke M, Ahrens H, Streitbuerger A et al (2009) Treatment options for recurrent giant cell tumors of bone. J Cancer Res Clin Oncol 135(1):149\u0026ndash;158. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00432-008-0427-x\u003c/span\u003e\u003cspan address=\"10.1007/s00432-008-0427-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTsukamoto S, Mavrogenis AF, Hindiskere S et al (2022) Outcome of reoperation for local recurrence following en bloc resection for giant cell tumor of bone of the extremity. Curr Oncol 29(9):6383\u0026ndash;6399. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/curroncol29090503\u003c/span\u003e\u003cspan address=\"10.3390/curroncol29090503\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLipplaa A, Dijkstra S, Gelderblom H (2019) Challenges of denosumab in giant cell tumor of bone and other giant cell-rich tumors of bone. Curr Opin Oncol 31(4):329\u0026ndash;335. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/CCO.0000000000000529\u003c/span\u003e\u003cspan address=\"10.1097/CCO.0000000000000529\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKlenke FM, Wenger DE, Inwards CY, Rose PS, Sim FH (2011) Giant cell tumor of bone: Risk factors for recurrence. Clin Orthop Relat Res 469(2):591\u0026ndash;599. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11999-010-1501-7\u003c/span\u003e\u003cspan address=\"10.1007/s11999-010-1501-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTeixeira LEM, Vilela JCS, Miranda RH, Gomes AH, Costa FA, de Faria VC (2014) Giant cell tumors of bone: Nonsurgical factors associated with local recurrence. Acta Orthop Traumatol Turc 48(2):136\u0026ndash;140. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3944/AOTT.2014.2714\u003c/span\u003e\u003cspan address=\"10.3944/AOTT.2014.2714\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eErrani C, Tsukamoto S, Leone G et al (2017) Higher local recurrence rates after intralesional surgery for giant cell tumor of the proximal femur compared to other sites. Eur J Orthop Surg Traumatol 27(6):813\u0026ndash;819. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00590-017-1983-z\u003c/span\u003e\u003cspan address=\"10.1007/s00590-017-1983-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eViswanathan S, Jambhekar NA (2010) Metastatic giant cell tumor of bone: Are there associated factors and best treatment modalities? Clin Orthop Relat Res 468(3):827\u0026ndash;833. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11999-009-0966-8\u003c/span\u003e\u003cspan address=\"10.1007/s11999-009-0966-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlgawahmed H, Turcotte R, Farrokhyar F, Ghert M (2010) High-speed burring with and without the use of surgical adjuvants in the intralesional management of giant cell tumor of bone: A systematic review and meta-analysis. Sarcoma 2010:586090. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1155/2010/586090\u003c/span\u003e\u003cspan address=\"10.1155/2010/586090\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu YP, Li KH, Sun BH (2012) Which treatment is the best for giant cell tumors of the distal radius? A meta-analysis. Clin Orthop Relat Res 470(10):2886\u0026ndash;2894. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11999-012-2464-7\u003c/span\u003e\u003cspan address=\"10.1007/s11999-012-2464-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZou C, Lin T, Wang B et al (2019) Management of giant cell tumor within the distal radius: A retrospective study of 58 cases from a single center. J Bone Oncol 14:100211. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jbo.2018.100211\u003c/span\u003e\u003cspan address=\"10.1016/j.jbo.2018.100211\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKoucheki R, Gazendam A, Perera J et al (2023) Management of giant cell tumors of the distal radius: A systematic review and meta-analysis. Eur J Orthop Surg Traumatol 33(4):759\u0026ndash;772. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00590-022-03252-9\u003c/span\u003e\u003cspan address=\"10.1007/s00590-022-03252-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Giant cell tumor of bone, recurrence, intralesional curettage, wide resection, denosumab, musculoskeletal oncology","lastPublishedDoi":"10.21203/rs.3.rs-7879093/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7879093/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose:\u003c/h2\u003e\u003cp\u003eThe optimal management of recurrent giant cell tumor of bone (GCTB) remains controversial, particularly regarding the choice between repeat intralesional surgery and wide resection. This study aimed to analyze the effects of tumor localization, demographic factors, and surgical strategies on secondary recurrence in patients treated for recurrent GCTB.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e\u003cp\u003eA retrospective review was conducted on 45 patients surgically treated for recurrent GCTB between 2005 and 2020. Thirteen patients were excluded due to insufficient follow-up or incomplete radiological data, leaving 32 patients eligible for analysis. Data regarding patient demographics, tumor characteristics, primary treatment center, surgical method for recurrence, neoadjuvant denosumab use, and oncologic outcomes were collected. Recurrence-free survival (RFS) was evaluated using Kaplan\u0026ndash;Meier analysis, and factors affecting secondary recurrence were assessed using univariate statistics.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e\u003cp\u003eThe mean age at recurrence surgery was 32.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7 years, with a mean follow-up of 87.5 months. Secondary recurrence occurred in 11 patients (34.4%) at a mean interval of 23.8 months. The secondary recurrence rate was higher in the repeat intralesional curettage group (38%) compared with the wide resection group (16%). Extracompartmental extension was significantly associated with recurrence (36% vs. 23%). Secondary recurrence developed in 28% of patients who received neoadjuvant denosumab and in 36% of those who did not. Pulmonary metastases occurred in 15.6% of cases. The 2-year and 5-year RFS rates were 84% and 72%, respectively, and the mean MSTS functional score was 25.6 (85.3%).\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e\u003cp\u003eWide resection offers superior local control in recurrent GCTB compared with repeat curettage; however, extended curettage with adjuvants remains a viable joint-preserving option in selected cases. Extracompartmental extension and distal radius localization were associated with an increased risk of re-recurrence. Initial treatment quality and surgeon experience appear to influence oncologic outcomes, supporting early referral to specialized musculoskeletal oncology centers. Long-term follow-up is essential due to the risk of recurrence and pulmonary metastasis.\u003c/p\u003e","manuscriptTitle":"Does initial surgical treatment influence the management of recurrent giant cell tumor of bone?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-06 08:32:26","doi":"10.21203/rs.3.rs-7879093/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"eb14e275-4abe-434a-b6e8-bcf575794c8b","owner":[],"postedDate":"November 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-31T10:09:00+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-06 08:32:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7879093","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7879093","identity":"rs-7879093","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}