Local control of giant cell tumors of the long bone after aggressive curettage with and without bone cement

Giant cell tumors (GCTs) are primary benign bone tumors with invasive and potentially malignant characteristics [1‐3]. Intralesional curettage is the main surgical treatment option [4, 5]. After curettage, filling the cavity with bone grafts or cement is commonly performed to provide structural support and prevent collapse [6]. Previous studies have shown that using bone cement as a filler can significantly reduce the relapse rate after curettage [7‐9]. In recent years, with the application of aggressive curettage technology, which is characterized by the use of a high-speed burr and other auxiliary methods, the giant cell tumor recurrence rate has been well controlled, and there is a new argument regarding the best type of implant material to use after aggressive curettage [10‐12]. It is well known that the GCT outcome may differ according to many factors, including the presence of metastatic disease at diagnosis, pathological fracture, soft tissue involvement, and anatomical site [7, 13, 14]. Therefore, it is very difficult to make a reliable assessment regarding the role of different implant materials, and it is important to assess the role of different implant materials in a group of patients with the same or similar clinical conditions.

The aim of this study was to retrospectively review our experience with GCTs in patients with similar clinical conditions by assessing the contribution of different implant materials to local control and functional results.

GCTs of the bone are aggressive and potentially malignant primary bone tumors that often occur at the end of the long bone in adults aged 20 ~ 40 years old [18, 19]. These tumors are primarily composed of stromal cells and multinucleated giant cells; the stromal cells are the main tumor cell component in GCTs of the bone [20, 21]. According to microscopic morphological findings, Jaffe created a pathological classification system for GCTs, including grades I-III. In the new bone tumor classification released by the WHO in 2002, GCTs of the bone were divided into GCTs and malignant GCTs. The former are equivalent to grades I ~ II, and the latter is equivalent to grade III.

Surgical treatment options include intralesional excision or segmental resection [7, 14]. Curettage has a higher recurrence rate [22, 23], but it preserves adjacent joint function. The ideal treatment of GCTs consists of excising the tumor and sparing the joint. Therefore, many scholars believe that GCTs should be treated using curettage [24, 25]. To avoid local recurrence, aggressive curettage has been widely used and has achieved good clinical results [12, 14]. The recommended aggressive curettage technique involves opening the bone through a large cortical window that allows visualization of the entire tumor cavity. After curettage is achieved, the cavity is deepened with the use of high-speed burrs [14, 26]. Various adjuvant therapies (including phenol and liquid nitrogen) may be employed in conjunction with curettage, and these most likely reduce the risk of recurrence compared with curettage alone [19, 25].

After tumor evacuation, the cavity can be filled with cement or bone grafting [10]. The literature is divided as to whether the bone defect should be filled using bone grafts or cement. In the Scandinavian Sarcoma Group multicenter study by Kivioja et al. [8], which involved 294 patients, filling the cavity with cement was shown to be a prognostic factor. The recurrence rate was 20% for filling with cement and 56% for intralesional surgery without cementation (p = 0.001). Becker WT et al. [13] has also reported that the use of bone cement as an adjuvant significantly reduces the recurrence rate following intralesional treatment of benign giant cell tumors, and it appears to be the therapy of choice for primary as well as recurrent giant cell tumors of the bone. By contrast, in the Canadian multicenter study by Turcotte et al. [11], which involved 186 patients, the adjuvant method or filling material was not significantly associated with the risk of recurrence. By retrospectively reviewing the records and images of 621 extremity GCT patients between 1989 and 2009, Niu X et al. [12] also concluded that bone grafting did not affect local tumor control after aggressive curettage and that the local recurrence rate was 11.1% if bone grafting was used. Similar results were also reported by Errani C et al. [14]; although cement decreased local recurrence, the influence of adjuvants was not statistically significant.

Many factors might influence the treatment outcome of GCTs [7, 13, 27], and none of these studies were randomized. Therefore, the evaluation of prognostic factors and the assessment of different local treatments may be affected by selection bias. Errani C [14] stated that no prospective randomized studies have shown the effects of different methods of filling the cavity. However, the main shortcoming of these retrospective reviews is the analysis of patients over a long time period, over which many changes in imaging studies, pathological examinations, and surgical treatments occurred, altering the diagnostic approach and treatment of patients with GCTs.

To avoid this problem, we used detailed patient selection criteria for this retrospective study performed for 2004–2009, including patients who underwent aggressive curettage. The operative procedure was also limited to three senior surgeons in our department. Our retrospective review attempted to identify prognostic factors useful to evaluate the risk level for each patient and possibly determine the strategies of GCT treatment.

After the univariate analysis, no significant statistical effect on the local recurrence rate was observed for gender, age, tumor volume, or Jaffe grade. Only the type of implant materials emerged as a significant factor. Bone cement was shown to be more effective at treating GCT compared with bone grafting. The Kaplan–Meier and log-rank life table analysis also confirmed that local cement treatment was significantly associated with a higher probability of better events and a better outcome. Regarding our patients’ clinical features, the only significant difference between the two groups was tumor volume (Table 2); in the bone grafting group, tumor volume was significantly smaller compared to the cement group (P < 0.001). Patients with small primary tumors might have a better prognosis and be more likely to be cured by bone grafting. However, bone grafting patients with smaller tumors relapsed more often compared to the cement group, which further suggests that bone cement is an effective adjuvant to treat GCT of the long bone, even for larger tumors.

Similar to marginal excision, it is difficult to completely remove residual tumor cells in the inner wall of the cavity using aggressive curettage, and there is still the possibility of relapse. Compared with bone grafting, bone cement can be combined with firmly scraping the edges of the residual cavity. When bone cement solidifies, it releases polymerizing heat reaching 80-90°C, which has a high-temperature inactivation effect on the residual cavity of the tumor [28, 29]. These factors are most likely the main reasons for the lower recurrence rate with bone cement fillings compared to bone grafting. We also found an abnormal banded signal around the area filled with bone cement by MRI (Figure 4A,B), which could reflect damage to the surrounding bone marrow due to the high-temperature effect. Howerer, there was no similar MRI findings in the bone grafting group (Figure 4C,D).

In most cases, the tumor recurred during the first two years (81.3%) after surgery in our series, which is consistent with other studies [1, 14], but the longest recurrence required 5 years to develop. Therefore, we suggest that patients should be evaluated through at least the 5th year after the final surgery. The data also showed that the GCT recurrence rates were 66.7% for bone grafting and 50% for bone cement one year after surgery, while they were 83.3% for bone grafting and 75% for bone cement in the first two years. These data indicate that the different implants and different postoperative times may lead to differences in the tumor recurrence rate following aggressive curettage of giant cell tumors of the long bone.

In other studies, tumor location significantly affected prognosis. Due to the difficulty associated with treatment, the distal radius and proximal femur are associated with a higher rate of local recurrence [14, 30]. However, there was no statistical correlation between tumor location and prognosis in our series.

For giant cell tumors of the long bones, the theoretical advantages of bone grafting, if the tumor does not relapse, include the ability of autologous or allograft bone to achieve bone healing, satisfactory recovery and no revisions. In contrast to our expectation, better functional results were observed in the cement group compared to the bone grafting group (P = 0.011) in our series. This discrepancy may due to the early weight-bearing activities of cement group patients and the short follow-up period during which bone cement-related complications, such as osteoporosis, were observed less often.

The limitations of our study include the retrospective analysis and the lack of random assignment of the type implant material used due to the tailored choice made according to each patient’s requirements.

In conclusion, we showed that the use of bone cement in a group of patients with GCTs of the long bone resulted in a lower local recurrence rate when compared to bone graft patients following aggressive intralesional curettage treatment. Better MSTS functional results were also observed after bone cement compared to the bone graft group. A prospective randomized study evaluating the effects of different methods of filling the cavity should be performed in the near future.