What is the treatment for Giant Cell Tumor (GCT) of bone?

Treatment of Giant Cell Tumor of Bone

Surgery is the treatment of choice for resectable GCTB, with intralesional curettage preferred for most stage I and II tumors to preserve joint function, while denosumab is indicated for unresectable disease, surgically morbid cases, or metastatic disease. 1

Initial Management Principles

All patients with GCTB must be managed by a bone sarcoma multidisciplinary team (MDT) at a specialized center. 1 Before proceeding with any treatment, exclude brown tumors of hyperparathyroidism by checking serum calcium levels. 1

Surgical Treatment Algorithm

For Resectable Disease

Intralesional curettage is the preferred surgical approach for most stage I and II tumors because it preserves joint function despite higher recurrence rates (12-65%) compared to wide excision (0-12%). 1, 2

• Enhance local control by using surgical adjuvants including high-speed burring, polymethylmethacrylate cement, and cryotherapy during curettage. 1
• The choice between curettage and en-bloc excision depends on whether joint preservation is possible, the size of any soft tissue mass, and weighing treatment morbidity against recurrence risk. 1

Reserve wide en-bloc excision for aggressive stage III tumors with extraosseous extension or when curettage is not feasible, accepting the trade-off of lower recurrence but worse functional outcomes and more surgical complications. 1

Special Surgical Considerations

• For pathological fractures, attempt joint preservation and curettage when possible. 3
• For pelvic and spinal GCTB, consider preoperative denosumab to reduce extraosseous lesions, harden the tumor, and facilitate en-bloc resection. 3
• For sacral GCTB, nerve-sparing surgery after embolization is a viable treatment option. 3

Denosumab Therapy

Indications

Denosumab is indicated when:

• Surgery is not possible or would be unacceptably morbid 1
• Patients have metastatic disease 1
• Selected cases before surgery to solidify the soft tissue component, facilitating surgical resection 1

Dosing and Administration

Give denosumab 120 mg subcutaneously monthly after three loading doses at weekly intervals (days 1,8, and 15). 1, 2

All patients require:

• Daily calcium and vitamin D supplementation 1
• Adequate contraception to avoid pregnancy 1

Critical Denosumab Considerations

If using denosumab preoperatively, plan for complete resection rather than curettage because curettage after denosumab is technically difficult and associated with higher local recurrence rates. 1

Optimal preoperative treatment duration is up to 6 months for responding tumors. 1

For inoperable tumors requiring long-term denosumab:

• Initial control is excellent (96%), but most tumors recur approximately 9 months after stopping the drug 1
• Patients with metastatic disease may require life-long treatment 1
• After 2 years of stable disease, consider increasing dosing intervals from 4-weekly to 8-weekly 1

Denosumab Side Effects

Monitor for hypocalcemia, osteonecrosis of the jaw, and atypical fractures. 1

Alternative Therapies for Unresectable Disease

Radiation Therapy

Radiotherapy achieves approximately 80% local control rates when surgery is unacceptably morbid or adequate margins are difficult to achieve, though control rates are lower in heavily pre-treated patients. 1

• Use specialized techniques such as 3-dimensional conformal RT or IMRT for locations not amenable to complete surgical resection 1
• Be aware that radiotherapy carries risk of malignant transformation (occurring in 1-3% of cases), so reserve it for cases where surgery is impossible and denosumab is not available 3, 4

Other Options

Serial arterial embolization is effective for tumors of the extremities with large cortical defects or joint involvement, and for large sacral GCTBs. 1

Management of Metastatic Disease

For pulmonary metastases, initial observation is recommended, then administer denosumab for growing lesions. 3

Surgery for pulmonary metastases is usually not performed. 1

Malignant Giant Cell Tumors

This is a critical distinction: Malignant transformation occurs in 1-3% of GCTBs and requires completely different management. 5, 4

For malignant GCTB:

• Do NOT use denosumab - this is the most critical error to avoid 5
• Use combination cytotoxic chemotherapy following osteosarcoma protocols (doxorubicin, cisplatin, high-dose methotrexate, ifosfamide) 1, 5
• Perform complete en-bloc resection with wide margins 5
• Intralesional curettage is NOT appropriate 5

Common Pitfalls to Avoid

• Never biopsy a suspected bone tumor before referral to a bone sarcoma center - refer BEFORE biopsy 2
• Do not use denosumab for malignant GCTB - it provides no benefit and delays appropriate treatment 5
• Avoid curettage after denosumab - plan for complete resection instead due to higher recurrence risk 1
• Do not use chemotherapy for conventional (non-malignant) GCTB - there are no randomized trials supporting this, and it is not standard of care 1