Abstract
BACKGROUND: The outcome of patients with osteosarcoma after relapse is very poor, with a 5-year overall survival (OS) below 30%. Prognostic factors in this setting remain poorly defined, limiting treatment decisions. This study identifies key clinical and biological prognostic factors to guide future trials. METHODS: A systematic review and meta-analysis included studies published between 1976 and 2022 with ≥35 patients. Searches were performed in MEDLINE/PUBMED, EMBASE, and Cochrane. Study quality was assessed using QUIPS tool. Studies reporting any clinical outcomes in the post-relapse setting were included. RESULTS: Nineteen studies involving 3245 patients were analysed. Nine prognostic factors were identified: relapse-free interval, site, number and size of lesions, resectability, sex, age, alkaline phosphatase levels and response to chemotherapy. Meta-analysis confirmed bilateral lung metastases worsened OS (HR 1.68, 95% CI 1.42-1.99). A relapse-free interval >24 months and complete surgical resection were consistently associated with better outcomes. Results on chemotherapy use were inconsistent. Substantial heterogeneity and low methodological quality were noted across studies. CONCLUSIONS: Key prognostic factors should address clinical trial design. Stratification by resectability, number and site of lesions and relapse-free interval is essential to evaluate treatment efficacy. Standardised protocols are needed to improve outcomes and provide tailored strategies for relapsed osteosarcoma.