What is the best treatment for a giant cell tumor on the distal femur?

Treatment of Giant Cell Tumor of the Distal Femur

Intralesional curettage with surgical adjuvants is the preferred treatment for most resectable giant cell tumors of the distal femur, as it balances local control with preservation of joint function and minimizes surgical morbidity. 1

Surgical Treatment Algorithm

Primary Surgical Approach

For stage I and II tumors (most cases):

• Intralesional curettage with adjuvants is the treatment of choice 1, 2
• Surgical adjuvants include high-speed burring, polymethylmethacrylate (cement), phenol, ethanol, or liquid nitrogen 1, 3
• This approach preserves joint function while achieving acceptable local control 1, 2
• Recurrence rates range from 12-50% with curettage plus adjuvants, but most patients (84%) are ultimately cured after one to three intralesional procedures 3, 4

For stage III tumors with extraosseous extension:

• En bloc wide excision is indicated 1
• This achieves lower recurrence rates (0-12%) but results in worse functional outcomes and more surgical complications 1, 2
• Reconstruction typically requires prosthetic replacement 5

Critical Surgical Considerations

• Pathological fractures are NOT a contraindication to intralesional curettage 3
• The distal femur location does not appear to increase recurrence risk compared to other sites (unlike proximal femur or distal radius) 3
• Wide excision should be reserved only for truly aggressive tumors where limb salvage with adequate margins is achievable 1

Role of Denosumab

Indications for Denosumab

Denosumab 120 mg subcutaneously is indicated for: 1, 6

• Unresectable tumors where surgery would result in severe morbidity
• Metastatic disease (rare, occurs in ~5% of cases)
• Selected cases as neoadjuvant therapy to facilitate surgical resection 1

Dosing Schedule

• 120 mg every 4 weeks with additional doses on days 8 and 15 of the first month 1, 6
• All patients require daily calcium and vitamin D supplementation 1, 6

Neoadjuvant Denosumab: Important Caveats

The use of preoperative denosumab is controversial and should be limited to expert centers: 1

• If used preoperatively, surgery should be performed after a few months of treatment (typically 4-6 months) 1
• Extensive ossification occurs with prolonged treatment, making it difficult to define tumor extent 1
• Curettage after denosumab is associated with HIGHER recurrence rates 1, 4
• If denosumab is used preoperatively, complete en bloc resection is preferred over curettage 1
• Recent evidence shows 29-42% recurrence rates even with neoadjuvant denosumab followed by curettage 4

Denosumab Side Effects to Monitor

• Hypocalcemia (can be severe and fatal) - monitor calcium levels especially in first weeks 1, 6
• Osteonecrosis of the jaw - perform oral examination before starting, avoid invasive dental procedures during treatment 1, 6
• Atypical femoral fractures 1, 6
• Rebound hypercalcemia after discontinuation 1, 6

Duration of Treatment

• For unresectable tumors, most require life-long treatment as discontinuation leads to progression after approximately 9 months 1
• Preliminary evidence suggests intervals can be extended from 4-weekly to 8-weekly after 2 years of stable disease 1

Radiation Therapy

Radiation therapy is NOT first-line treatment but has specific indications: 1

• Reserved for marginally resected, unresectable, progressive, or recurrent disease where surgery is not feasible 1
• Achieves 5-year local control rates of 85% and overall survival of 94% 1
• Doses of 40 Gy or less are associated with worse local control 1
• Advanced techniques (3D conformal RT, IMRT) improve outcomes for anatomically challenging locations 1
• Critical warning: Radiation carries risk of malignant transformation (1-3% of cases) 1

Management of Recurrent Disease

Local recurrences occur most commonly in the first 2-3 years: 7

• Repeat intralesional curettage with adjuvants is appropriate for most recurrences 3
• The majority of patients (84%) achieve cure after one to three intralesional procedures 4
• En bloc resection should be considered if repeated curettage fails or for aggressive recurrences 1

What NOT to Do: Critical Pitfalls

1. Do NOT use denosumab for malignant giant cell tumors (1-3% of cases transform to high-grade sarcoma) - these require osteosarcoma-based chemotherapy protocols 8
2. Do NOT perform internal fixation of pathological fractures before definitive tumor treatment 1
3. Do NOT perform curettage after prolonged denosumab treatment - this increases recurrence risk; prefer en bloc resection 1
4. Do NOT stop denosumab abruptly in unresectable cases - this leads to rapid progression 1

Functional Outcomes

• Intralesional curettage preserves better function than wide excision 1, 2
• Median MusculoSkeletal Tumor Society scores after treatment are typically 28/30 4
• Most patients return to good functional status with appropriate surgical technique 4

Follow-Up Strategy

• Monitor for local recurrence every 2-3 months for the first 2-3 years (peak recurrence period) 8, 7
• Chest imaging to monitor for pulmonary metastases (occurs in ~5% of cases) 1
• Long-term surveillance required as malignant transformation can occur 5-10+ years after initial treatment 1