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

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BackgroundRecurrence after osteosarcoma usually leads to death; thus prognostic factors for survival are of great importance. MethodsBetween 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 75mg/m2 and cisplatin 100mg/m2. The comparators were additional high-dose methotrexate (BO02), 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. ResultsMedian recurrence-free survival was 31months; 8 recurrences were reported more than 5years after the diagnosis. In 564 patients with a recurrence (median 13months post-randomisation), there was no difference in post-relapse survival between treatment arms. Patients whose disease recurred within 2years after randomization had a worse prognosis than those recurring after 2years. Patients with good initial histological response to pre-operative chemotherapy had a 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 the 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 5years). ConclusionsThese data describing a large series of patients with recurrent extremity osteosarcoma 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.