Survival after recurrent osteosarcoma: Data from 3 European Osteosarcoma Intergroup (EOI) randomized controlled trials

Background: Recurrence after osteosarcoma usually leads to death; thus prognostic factors for survival are of great importance. Methods: Between 1983 and 2002, the European Osteosarcoma Intergroup accrued 1067 patients to 3 randomized controlled trials of pre- and post-operative chemotherapy for patients with resectable non-metastatic high-grade osteosarcoma of the extremity. Control treatment in all trials was doxorubicin 75 mg/m(2) and cisplatin 100 mg/m(2). The comparators were additional high-dose methotrexate (8002), T10-based multi-drug regimen (BO03) and G-CSF intensified-DC (BO06). Post-recurrence survival (PRS) was investigated on combined data with standard survival analysis methods. Results: Median recurrence-free survival was 31 months; 8 recurrences were reported more than 5 years after diagnosis. In 564 patients with a recurrence (median 13 months post-randomisation), there was no difference in post-relapse survival between treatment arms. Patients whose disease recurred within 2 years after randomization had worse prognosis than those recurring after 2 years. Patients with good initial histological response to preoperative chemotherapy had better overall survival after recurrence than poor responders. Local relapse was more often reported after limb-saving procedures (2 versus 8%; amputation versus limb-saving), independent of primary tumour site. Site of first recurrence (local 20%, lung 62%, "other" 19%) affected survival, as patients recurring with non-lung distant metastases only or any combination of local relapse, lung metastases and non-lung metastases (=group "other") had significantly worse overall survival (local 39%, lung 19%, "other" 9% at 5 years). Conclusions: These data describing a large series of patients with recurrent extremity ostesarcoma confirm the relationship between early recurrence and poor survival. There was better PRS in patients after good histological response to pre-operative chemotherapy, or with local-only recurrence. (C) 2010 Elsevier Ltd. All rights reserved.