Prognostic Factors in Newly Diagnosed High-Grade Osteosarcoma-A Systematic Review

Introduction: Pretreatment prognostic factors in newly diagnosed osteosarcoma are important for clinical management and stratifying patients in clinical trials. Such factors include the presence of metastases, primary tumor size, and site. Factors surrounded by controversy include pathological fracture, histologic subtype, and P-glycoprotein expression. No prognostic tumor biomarker has been established. We performed a systematic review with the aim to compile available evidence for pretreatment prognostic factors and define optimal cut-off values for patient stratification or further validation in the upcoming European FOSTER-CabOS trial. Methods: Predefined search terms were used to search PubMed, Web-of-science, and Embase for all studies investigating pretreatment prognostic factors in newly diagnosed osteosarcoma patients published 2000–2023. After applying strict inclusion and exclusion criteria, 49 papers were included. Results: We found 14 factors investigated in at least two separate studies or in a single study using one discovery and at least one validation cohort. Conclusions: We confirmed the prognostic value of patient age, presence of metastasis, tumor size, and site (axial vs. appendicular). Future studies of these factors should focus on specific patient populations and defining optimal cut-off values. Although serum level of alkaline phosphatase and lactate dehydrogenase were associated with outcome, it remains unclear if they are independent of other prognostic factors. The prognostic value remains unclear for sex, pathological fracture, histologic subtype, and P-glycoprotein expression. We could not establish any new prognostic biomarker. However, circulating tumor DNA in plasma and the G1/G2 RNA signature in diagnostic tumor biopsies show promise and will be further validated in the upcoming FOSTER-CabOS trial.