Recurrence of Ewing sarcoma is most common within 2 years of initial diagnosis (approximately 80%).[1,2] However, late relapses occurring more than 5 years from initial diagnosis are more common in Ewing sarcoma (13%; 95% confidence interval, 9.4–16.5) than in other pediatric solid tumors. The overall prognosis for patients with recurrent Ewing sarcoma is poor; 5-year survival following recurrence is approximately 10% to 15%.[2,4,5]; [Level of evidence: 3iiA] Time to recurrence is the most important prognostic factor. Patients who recurred greater than 2 years from initial diagnosis had a 5-year survival of 30% versus 7% for patients who recurred within 2 years.;  Patients with both local recurrence and distant metastases have a worse outcome than patients with either isolated local recurrence or metastatic recurrence alone.[1,2] Isolated pulmonary recurrence was not an important prognostic factor.
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
Incidence and Mortality
Note: Estimated new cases and deaths from testicular cancer in the United States in 2012:
New cases: 8,590.
The selection of treatment for patients with recurrent disease depends on many factors, including the site of recurrence and prior treatment, as well as individual patient considerations. Combinations of chemotherapy, such as cyclophosphamide and topotecan or irinotecan and temozolomide, are active in recurrent Ewing sarcoma and can be considered for these patients.[6,7,8,9,10] There is no standardized second-line treatment for relapsed or refractory Ewing sarcoma. One phase II study of topotecan and cyclophosphamide showed a response in 6 of 17 patients with Ewing sarcoma; 16 of 49 patients had a clinical response in a similar trial from Germany.[6,8] In one retrospective series, 20 patients received temozolomide and irinotecan following recurrence. Five patients achieved a complete response and seven patients achieved a partial response. The combination of gemcitabine and docetaxel has achieved objective responses in relapsed Ewing sarcoma.[Level of evidence: 3iiiDiv] High-dose ifosfamide (3 g/m2 /day for 5 days = 15 g/m2) has shown activity in patients who recurred after therapy which included standard ifosfamide (1.8 g/m2 /day for 5 days = 9 g/m2).[Level of evidence: 3iiiDiv]
Aggressive attempts to control the disease, including myeloablative regimens, have been used, but there is no evidence at this time to conclude that myeloablative therapy is superior to standard chemotherapy.[13,14]; [Level of evidence: 3iiiDiii] Surveys of patients undergoing allogeneic stem cell transplantation for recurrent Ewing sarcoma did not show improved event-free survival when compared with autologous stem cell transplantation and was associated with a higher complication rate.[13,16,17]
Monoclonal antibodies against the insulin-like growth factor 1 receptor (IGF1R) are reported to produce objective responses in metastatic recurrent Ewing sarcoma in roughly 10% of cases.[18,19,20,21][Level of evidence: 3iiDiv] In these studies, it was suggested that time-to-progression was prolonged compared with historical controls. Further studies are needed to identify patients who are likely to benefit from IGF1R therapy.