Prognostic factors in patients with relapsed high-grade osteosarcoma: a systematic review.

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.