Approximately 50% of relapses occur within 18 months of therapy termination, and only 5% of recurrences develop beyond 5 years.[1,2,3,4] In 564 patients with a recurrence, patients whose disease recurred within 2 years of diagnosis had a worse prognosis than did patients whose disease recurred after 2 years. Patients with a good histologic response to initial preoperative chemotherapy had a better overall survival (OS) after recurrence than did poor responders. The probability of developing lung metastases at 5 years is 28% in patients presenting with localized disease. In two large series, the incidence of recurrence by site was as follows: lung only (65%-80%), bone only (8%-10%), local recurrence only (4%-7%), and combined relapse (10%-15%).[4,6] Abdominal metastases are rare but may occur as late as 4 years after diagnosis.
Patients with recurrent osteosarcoma should be assessed for surgical resectability, because they may sometimes be cured with aggressive surgical resection with or without chemotherapy.[8,6,9,10,11,12] Control of osteosarcoma after recurrence depends on complete surgical resection of all sites of clinically detectable metastatic disease. If surgical resection is not attempted or cannot be performed, progression and death are certain. The ability to achieve a complete resection of recurrent disease is the most important prognostic factor at first relapse, with a 5-year survival rate of 20% to 45% after complete resection of metastatic pulmonary tumors and a 20% survival rate after complete resection of metastases at other sites.[4,6,12,13]
The role of systemic chemotherapy for the treatment of patients with recurrent osteosarcoma is not well defined. The selection of further systemic treatment depends on many factors, including the site of recurrence, the patient's previous primary treatment, and individual patient considerations. Ifosfamide alone with mesna uroprotection, or in combination with etoposide, has been active in as many as one-third of patients with recurrent osteosarcoma who have not previously received this drug.[14,15,16,17] Cyclophosphamide and etoposide are active in recurrent osteosarcoma, as is the combination of gemcitabine and docetaxel.[18,19,20] The Italian Sarcoma Group reported rare objective responses and disease stabilization with sorafenib in patients with recurrent osteosarcoma. Peripheral bloodstem cell transplant utilizing high-dose chemotherapy does not appear to improve outcome. High-dose samarium-153-ethylenediamine tetramethylene phosphonic acid (EDTMP) coupled with peripheral bloodstem cell support may provide significant pain palliation in patients with bone metastases.[22,23,24,25] Toxicity of samarium-153-EDTMP is primarily hematologic.[Level of evidence: 3iiDiii]