Osteosarcoma Treatment Approach
Recommended Treatment Strategy
Pediatric and young adult patients with osteosarcoma should receive multiagent neoadjuvant chemotherapy followed by complete surgical resection with wide margins, then adjuvant chemotherapy for a total treatment duration of 6-12 months. 1
Initial Diagnostic Workup
Before initiating treatment, patients require comprehensive staging:
- Imaging: CT chest for pulmonary metastases (most common site of spread), bone scintigraphy to rule out bone metastases, and MRI of the entire affected bone 1
- Laboratory assessment: Complete blood count, renal function (creatinine and GFR), electrolytes including magnesium, liver enzymes, alkaline phosphatase (ALP), and LDH 1
- Cardiac evaluation: Baseline echocardiogram prior to doxorubicin therapy 1
- Fertility preservation: Sperm banking should be considered before chemotherapy 1
Critical referral principle: Patients with radiological findings suggesting bone sarcoma should be referred to a specialized bone sarcoma center without prior biopsy 1. The biopsy must be performed by the surgeon who will perform definitive surgery, with the incision placed in an area that will be excised during resection 1.
Chemotherapy Regimen
Neoadjuvant Phase (Preoperative)
Standard chemotherapy consists of combinations of doxorubicin and cisplatin, with many centers adding ifosfamide and high-dose methotrexate with leucovorin rescue. 1
Acceptable regimen options include 1:
- High-dose methotrexate + doxorubicin
- Doxorubicin + cisplatin (MAP backbone)
- High-dose methotrexate + cisplatin + doxorubicin
- Ifosfamide + cisplatin
Duration: 4-6 courses of preoperative chemotherapy 1
High-Dose Methotrexate Specifications
- Pediatric dosing: At least 12 g/m² 1, 2
- Adult dosing: At least 8 g/m² (may use test dose to achieve identical AUC) 1
- Critical requirements: Facilities must provide rigorous hydration, ability to measure methotrexate levels, leucovorin rescue, regular blood tests, and dialysis capability if needed 1, 2
- Contraindication: NSAIDs should NOT be administered prior to or concomitantly with high-dose methotrexate due to risk of severe hematologic and gastrointestinal toxicity from elevated methotrexate levels 2
Surgical Management
Timing and Approach
Surgery should be performed after neoadjuvant chemotherapy, with repeat imaging of the primary tumor using all baseline modalities prior to surgery. 1
Surgical Principles
- Wide surgical margins are essential to avoid local recurrence, regardless of tumor response to chemotherapy 1
- Limb salvage procedures are performed in 80% of extremity tumors at specialist centers 1
- En bloc resection without opening the tumor, including excision of the biopsy scar 1
- Amputation only under exceptional circumstances when limb-sparing surgery is contraindicated 1
Histologic response evaluation: The pathologist plays a critical role in assessing response to preoperative chemotherapy, which provides important prognostic information 1. However, altering postoperative chemotherapy in poor responders has not been proven to improve outcome 1.
Adjuvant Chemotherapy (Postoperative)
Continue chemotherapy for 6-10 additional cycles using the same agents as preoperatively, for a total treatment time of 6-12 months. 1
Although preoperative chemotherapy has not been proven to add survival benefit over postoperative chemotherapy alone, the combined approach is preferred because it 1:
- Allows preparation for safe surgery
- Enables preparation of appropriate prosthesis
- Provides prognostic information through histologic response assessment
Prognostic Factors
Adverse prognostic indicators include 1:
- Detectable metastases at diagnosis
- Age >40 years
- Non-extremity localization
- Large tumor volume
- Elevated serum ALP or LDH
- Poor histological response to preoperative chemotherapy (<90% tumor necrosis)
Metastatic Disease Management
For patients with metastatic disease at presentation or recurrence, treatment should combine chemotherapy with metastasectomy. 1
- Pulmonary metastases: Complete surgical clearance of all metastases can achieve 40% 5-year survival with limited pulmonary relapse 1
- Repeated thoracotomies are often indicated for recurrent pulmonary disease 1
- Second-line chemotherapy options: High-dose methotrexate, ifosfamide, and etoposide (depending on primary treatment) 1
Survival Outcomes
Chemotherapy has significantly increased 5-year survival rates from 20% to 60% for patients with localized tumors as part of a multidisciplinary approach. 1
Patients with one or few resectable pulmonary metastases have survival rates approaching those with no metastatic disease 1.
Follow-Up Schedule
Surveillance intervals 1:
- Years 0-3: Every 3 months
- Years 3-5: Every 6 months
- Years 5-10: Every 8-12 months
- Pediatric patients: Should be followed longer due to long-term toxicity concerns 1
Required examinations: Chest radiological analyses at each visit 1
Critical Treatment Principles
All pediatric and young adult patients with osteosarcoma should be treated within prospective multicenter clinical trials at specialized centers with multidisciplinary teams including pediatric/medical oncologists, orthopedic surgeons, pathologists, and radiologists. 1, 3, 4
The combination of complete surgical resection with negative margins and intensive multiagent chemotherapy remains the cornerstone of curative treatment, with surgical remission and histologic response emerging as key prognostic factors. 1, 5, 3