Objectives: Investigating the effect of prognostic factors in a multistate framework on survival in a large population of patients with osteosarcoma. Of interest is how prognostic factors affect different disease stages after surgery, with stages of local recurrence (LR), new metastatic disease (NM), LR+NM, secondary malignancy, a second NM, and death.
Design: An open-label, international, phase 3 randomised controlled trial.
Setting: 325 sites in 17 countries.
Participants: The subset of 1631 metastases-free patients from 1965 patients with high-grade resectable osteosarcoma, from the European and American Osteosarcoma Study.
Main outcome measures: The effect of prognostic factors on different disease stages, expressed as HRs; predictions of disease progression on an individual patient basis, according to patient-specific characteristics and history of intermediate events.
Results: Of 1631 patients, 526 experienced an intermediate event, and 305 died by the end of follow-up. An axial tumour site substantially increased the risk of LR after surgery (HR=10.84, 95% CI 8.46 to 13.86) and death after LR (HR=11.54, 95% CI 6.11 to 21.8). A poor histological increased the risk of NM (HR=5.81, 95% CI 5.31 to 6.36), which sharply declined after 3 years since surgery. Young patients (<12 years) had a lower intermediate event risk (eg, for LR: HR=0.66, 95% CI 0.51 to 0.86), when compared with adolescents (12-18 years), but had an increased risk of subsequent death, while patients aged >18 had a decreased risk of death after event (eg, for death after LR: HR=2.40, 95% CI 1.52 to 3.90; HR=0.35, 95% CI 0.21 to 0.56, respectively).
Conclusions: Our findings suggest that patients with axial tumours should be monitored for LR and patients with poor histological response for NM, and that for young patients (<12) with an LR additional treatment options should be investigated.
Trial registration number: NCT00134030.
Keywords: bone diseases; clinical trials; paediatric oncology; sarcoma.
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.