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

Treatment of Osteosarcoma of the Right Knee

Osteosarcoma of the right knee requires multimodal treatment with neoadjuvant chemotherapy followed by limb-salvage surgery with wide margins, then adjuvant chemotherapy—this approach increases disease-free survival from 10-20% to over 60% compared to surgery alone. 1

Initial Management and Referral

• Immediate referral to a specialized bone sarcoma reference center is mandatory before any biopsy or further intervention, as management complexity requires multidisciplinary expertise including orthopedic oncology, medical oncology, and specialized surgical reconstruction capabilities 1, 2
• Avoid weight-bearing on the affected extremity to prevent pathologic fracture, which disseminates tumor cells and increases local recurrence risk 1, 3
• If pathologic fracture exists, use external splintage only—internal fixation is contraindicated as it further disseminates tumor into bone and soft tissues 1

Staging Workup

Complete staging must be performed before treatment initiation 1:

• Local imaging: Plain radiographs and MRI of the entire affected extremity to assess tumor extent, soft tissue involvement, neurovascular proximity, and skip lesions 1
• Metastatic evaluation: Chest CT (high-resolution spiral preferred over plain radiographs), bone scintigraphy, and consider whole-body MRI or PET-CT 1
• Laboratory markers: Alkaline phosphatase (AP) and lactate dehydrogenase (LDH)—elevated levels correlate with adverse outcomes and are prognostic 1
• Pre-chemotherapy assessment: Complete blood count, renal function, echocardiogram or radionuclide ventriculography (baseline cardiac function), audiogram (for platinum-based therapy), liver function, and fertility preservation counseling 1

Chemotherapy Regimen

Standard Protocol for High-Grade Osteosarcoma

The backbone chemotherapy agents are doxorubicin, cisplatin, high-dose methotrexate (HD-MTX), and ifosfamide 1:

• For patients ≤40 years: MAP protocol (high-dose methotrexate with leucovorin rescue, doxorubicin, cisplatin) is standard 2
• For patients >40 years: Doxorubicin, cisplatin, and ifosfamide without HD-MTX is preferred, as older patients tolerate HD-MTX poorly 1, 2
• Treatment duration typically spans 6-10 months total 1

Neoadjuvant Phase

• Preoperative chemotherapy is administered first to facilitate surgical planning, allow tumor shrinkage, and assess histological response—though formal proof that preoperative timing improves survival per se is lacking 1
• Histological response to neoadjuvant chemotherapy is the most important prognostic factor: good responders (>90% necrosis) have significantly better survival than poor responders 1

Surgical Management

Timing and Approach

• Surgery should occur after neoadjuvant chemotherapy, performed by a surgical team experienced in complex reconstructive options 1
• Limb-salvage surgery is appropriate for most patients and should be prioritized over amputation when oncologically safe 1

Surgical Margins

The primary surgical goal is achieving wide margins (R0 resection) with complete tumor removal surrounded by an unviolated cuff of normal tissue, including the biopsy tract 1:

• Wide margins are critical—narrower (marginal or intralesional) margins significantly increase local recurrence risk, which correlates with reduced overall survival 1
• Mark areas of suspected close margins on the surgical specimen for pathology review 1
• Functional preservation is important but secondary to achieving adequate margins 1

Adjuvant Chemotherapy

• Postoperative chemotherapy continues with the same agents used preoperatively 1
• Current trials evaluate whether modifying postoperative chemotherapy in poor histological responders improves outcomes, though benefit remains unproven 1

Radiation Therapy

• Radiation has a very limited role in extremity osteosarcoma and should be reserved only for unresectable tumors or when adequate surgical margins cannot be achieved 1
• Consider advanced techniques (proton or carbon ion beam therapy) for unresectable primary tumors, preferably within clinical trials 1

Prognostic Factors

Poor prognostic indicators include 1:

• Detectable metastases at presentation (especially bone metastases)
• Proximal extremity or axial tumor location
• Large tumor size
• Elevated serum AP or LDH
• Older age
• Poor histological response to neoadjuvant chemotherapy (<90% necrosis)

Follow-Up Surveillance

Intensive surveillance is required given the high metastatic potential 2:

• Years 1-2: Every 3 months with local imaging and chest radiography/CT
• Years 3-5: Every 6 months
• Years 5-10: Every 6-12 months
• Beyond 10 years: Every 0.5-2 years, with continued monitoring for late chemotherapy/surgery/radiotherapy toxicities

Critical Pitfalls to Avoid

• Never perform biopsy or surgery outside a specialized bone sarcoma center—improper biopsy technique or surgical approach can compromise subsequent limb-salvage options 1, 2
• Do not use internal fixation for pathologic fractures—this disseminates tumor and increases recurrence 1
• Do not delay referral for complete staging workup, as treatment planning depends on accurate disease extent 1
• Ensure adequate supportive care infrastructure for HD-MTX administration, including meticulous leucovorin rescue protocols 1