What is the standard treatment approach for osteosarcoma (bone cancer) of the right knee?

Standard Treatment for Osteosarcoma of the Right Knee

The standard treatment for high-grade osteosarcoma of the right knee consists of multimodal chemotherapy combined with limb-sparing surgical resection, which increases disease-free survival from <20% to >60% compared to surgery alone. 1

Initial Staging and Workup

Before initiating treatment, comprehensive staging must be completed at a specialized bone sarcoma reference center 1:

• Local imaging: Plain radiographs and MRI of the entire affected extremity to define tumor extent 1
• Distant disease assessment: Chest CT scan (mandatory for pulmonary metastases), bone scintigraphy and/or whole-body MRI, and FDG-PET-CT/MRI as clinically indicated 1
• Laboratory markers: Baseline alkaline phosphatase (AP) and lactate dehydrogenase (LDH), which have prognostic value 1
• Biopsy: Must be performed under supervision of the surgical team or dedicated interventional radiologist to avoid contamination 1

Critical pitfall: Unplanned surgery or biopsy outside a reference center increases local recurrence rates (43.8% vs. 17.9%), causes earlier metastases, and reduces limb salvage rates (68.7% vs. 87.3%) 2. The knee is the most common site for osteosarcoma, typically arising in the distal femoral or proximal tibial metaphysis 1.

Chemotherapy Regimen

Neoadjuvant (Preoperative) Chemotherapy

The MAP regimen (high-dose methotrexate, doxorubicin, and cisplatin) is the most frequently used first-line treatment 1:

• High-dose methotrexate: At least 12 g/m² in children or 8 g/m² in adults, requiring mandatory inpatient treatment with rigorous hydration, methotrexate level monitoring, leucovorin rescue, and dialysis capability 1, 3
• Doxorubicin and cisplatin: Core components with established antitumor activity 1
• Ifosfamide: May be added as a fourth agent 1

Age-specific modification: In patients >40 years old, regimens often combine doxorubicin, cisplatin, and ifosfamide without high-dose methotrexate due to tolerability concerns 1. The two-drug combination of doxorubicin plus cisplatin may be comparable to more complex regimens when methotrexate cannot be used 1, 4.

Neoadjuvant chemotherapy is typically administered for 8-12 weeks before surgery 1. While formal proof is lacking that preoperative chemotherapy improves survival per se, it allows assessment of histological tumor response, which is a strong predictor of survival 1.

Surgical Management

Limb-Sparing Surgery

Most patients (90-95%) should be considered candidates for limb salvage rather than amputation 1, 5:

• Surgical goal: Complete tumor removal with wide, clear margins while preserving maximum function 1
• Margin importance: R1 (microscopically positive) and R2 (grossly positive) margins both increase local recurrence risk and reduce overall survival 1. Intralesional or marginal margins are associated with increased local relapse rates 1
• Surgical team: Must be experienced in bone tumor surgery with expertise in reconstructive options, particularly for skeletally immature patients requiring growth-preserving techniques 1, 6

Reconstruction Options

For the knee region, several approaches exist 1, 6:

• Endoprosthetic replacement: Suitable for tumors involving the epiphysis/physis (MRI types IV-V) 6
• Biological reconstruction (allograft or autograft): Preferred for epiphysis/physis preservation in growing patients (MRI types I-III) 6
• Rotationplasty: Alternative option in select cases 1

Surgical timing: Performed after neoadjuvant chemotherapy, typically at 8-12 weeks, with en bloc resection including the biopsy tract 1. Areas of suspected close margins must be marked on the surgical specimen for pathological assessment 1.

Adjuvant (Postoperative) Chemotherapy

Following surgery, chemotherapy continues using the same agents as preoperatively, with total treatment duration of 6-10 months 1. The histological response to preoperative chemotherapy (percentage of tumor necrosis) predicts survival and may guide postoperative treatment intensity, though altering chemotherapy in poor responders has not been definitively proven to improve outcomes 1.

Special Considerations

Pathological Fracture

If pathological fracture occurs 1:

• Avoid internal fixation: This disseminates tumor into bone and soft tissues, increasing local recurrence risk
• Use external splintage instead
• Proceed with neoadjuvant chemotherapy: Allows fracture hematoma to contract before resection
• Amputation is not mandatory: Limb salvage remains possible with appropriate management

Metastatic Disease at Presentation

Approximately 30% of patients with primary metastatic osteosarcoma can become long-term survivors with complete surgical resection of all disease sites 3, 4. These patients should be treated with curative intent following the same chemotherapy principles as non-metastatic disease, with aggressive surgical management of both primary tumor and metastases (typically pulmonary) 1, 4.

Radiotherapy

Radiotherapy is not standard for resectable osteosarcoma 1. It should only be considered for 1, 4:

• Unresectable primary tumors (high-dose 55-70 Gy, with photon or proton/carbon ion beam techniques)
• Inadequate surgical margins when re-resection is not feasible
• Palliation of locally recurrent disease

Prognostic Factors

Adverse prognostic indicators include 1:

• Detectable metastases at presentation
• Proximal extremity or axial tumor location (the knee is a relatively favorable site)
• Large tumor size
• Elevated serum AP or LDH
• Older age
• Poor histological response to neoadjuvant chemotherapy (<90% necrosis)

Follow-Up Surveillance

Recommended monitoring schedule 1:

• Years 1-2: Chest X-ray every 2 months; CT scan every 6 months if metastases were present at diagnosis
• Years 3-4: Chest X-ray every 3 months; CT scan every 6 months
• Years 5-6: Chest X-ray every 6 months
• Beyond year 6: Annual chest X-ray
• Local imaging: Plain radiographs and MRI only for symptoms
• Bone scintigraphy: Every 4 months for years 1-2, then every 6 months for years 3-4, though its role remains debatable 1

Long-term surveillance for chemotherapy, surgery, and radiotherapy toxicities should continue for >10 years 7.

Treatment Outcomes

With modern multimodal therapy, long-term survival and cure rates have increased to 60-80% in patients with localized disease 5. The Musculoskeletal Tumor Society functional scores typically range from excellent to fair 6. Common complications include delayed union (57% with biological reconstruction), infection and recurrence (each 17% with endoprosthesis), and limb-length discrepancy in growing patients 6.