What is the management of osteosarcoma?

Management of Osteosarcoma

The optimal management of osteosarcoma requires a multimodal approach with chemotherapy and surgery under the care of a specialized bone sarcoma multidisciplinary team (MDT), with MAP chemotherapy (methotrexate, doxorubicin, cisplatin) as the standard first-line treatment for patients under 40 years. 1

Diagnosis and Initial Assessment

• Imaging studies:

  • Plain radiographs: Show cortical destruction and irregular reactive bone formation
  • MRI with contrast: Best for defining tumor extent within bone and soft tissues
  • CT scan of chest: Essential for detecting pulmonary metastases
  • Bone scan: To identify additional synchronous lesions

• Laboratory tests:

  • Alkaline phosphatase (ALP) and lactate dehydrogenase (LDH): Often elevated and correlate with adverse outcomes 1
  • Complete blood count, renal and liver function tests, electrolytes
  • Hepatitis and HIV testing prior to chemotherapy

• Baseline assessments:

  • Cardiac function: Echocardiogram or radionuclide ventriculography
  • Audiogram: Due to potential ototoxicity from chemotherapy
  • Fertility preservation: Sperm storage for males of reproductive age 1

Treatment Algorithm for High-Grade Osteosarcoma

1. Non-metastatic Disease

• Preoperative (neoadjuvant) chemotherapy:

  • Standard regimen: MAP (high-dose methotrexate, doxorubicin, cisplatin) 1
  • Duration: Typically 2-3 months before surgery
  • For patients >40 years: Consider AP (doxorubicin, cisplatin) without methotrexate 1

• Surgery:

  • Goal: Complete tumor removal with negative margins (wide excision) 1
  • Limb salvage preferred when possible while ensuring adequate margins 1
  • Amputation only when necessary for complete tumor removal

• Postoperative (adjuvant) chemotherapy:

  • Continue MAP or AP regimen
  • Total duration of pre- and post-operative chemotherapy: 6-9 months 1
  • For patients <30 years: Consider adding mifamurtide 1

2. Metastatic Disease

• Same chemotherapy regimens as for non-metastatic disease 1
• Surgical approach:
  • Complete surgical removal of primary tumor AND all metastatic sites if feasible 1
  • For lung metastases: Thoracotomy with manual palpation of both lungs recommended 1
• Prognosis:
  • 30% overall survival for primary metastatic disease

  • 40% survival if complete surgical remission achieved 1

3. Recurrent Disease

• Surgical approach:

  • Complete surgical resection of all recurrent disease if possible 1
  • Repeated thoracotomies may be warranted for recurrent lung metastases 1

• Second-line chemotherapy options:

  • Ifosfamide and etoposide (highest response rates) 1
  • Gemcitabine and docetaxel
  • Oral etoposide for palliation
  • Consider multi-targeted tyrosine kinase inhibitors (cabozantinib, regorafenib, lenvatinib) through clinical trials or compassionate access 1

Special Considerations

Low-grade Osteosarcoma Variants

• Low-grade central, parosteal, and periosteal osteosarcoma:
  • Complete surgical removal only, without chemotherapy 1
  • Exception: If high-grade areas are found on resection, treat as conventional osteosarcoma 1

Craniofacial Osteosarcoma

• Management challenges:
  • Requires referral to bone sarcoma MDT before surgery 1
  • Chemotherapy is considered standard treatment 1
  • Consider radiotherapy (proton beam or IMRT) for:
    • Inoperable tumors
    • Close or positive margins
    • High risk of local recurrence 1

Older Patients

• Age-adapted approach:
  • Patients >40 years: Consider AP regimen without high-dose methotrexate 1
  • Surgery-first approach may be reasonable in older patients 1

Role of Radiotherapy

• Limited role in conventional osteosarcoma 1
• Consider for:
  • Inoperable tumors
  • Axial locations where complete resection is not feasible
  • Palliation of painful metastases 1

Prognostic Factors

• Poor prognostic indicators:
  • Proximal extremity or axial tumor site
  • Large tumor volume
  • Elevated ALP or LDH
  • Presence of metastases at diagnosis
  • Poor histological response to preoperative chemotherapy 1

Common Pitfalls to Avoid

• Delayed referral to specialized centers: All patients should be referred to specialized bone sarcoma centers before any surgical intervention 1
• Inadequate surgical margins: Narrow margins increase risk of local recurrence 1
• Overlooking metastatic disease: Thorough staging is essential before treatment initiation
• Inappropriate dose adjustments: High-dose methotrexate requires meticulous adherence to protocol guidelines 1
• Undertreatment of older patients: Multimodal therapy is beneficial up to at least age 60 1

The management of osteosarcoma has dramatically improved survival rates from 10-20% (with surgery alone) to >60% with modern multimodal treatment 1. Early referral to specialized centers and enrollment in clinical trials whenever possible are crucial to optimize outcomes.