Osteosarcoma is the most common type of primary bone malignancy in children and adolescents. The worldwide incidence is estimated at 3.4 cases per million people per year [1]. Osteosarcoma is usually located in the metaphysis of long bones, and it presents with bone pain that is usually accompanied by swelling, redness, limping, or pathologic fracture [2]. Approximately 10–20% of patients with osteosarcoma have measurable metastatic disease at diagnosis in the lungs, while 80% of them have non visible microscopic disease [3]. The 5-year overall relative survival of children and adolescents with osteosarcoma has been improved since the 1970 s, mainly due to the introduction of neoadjuvant and multiagent chemotherapy. Osteosarcoma chemotherapy is based on methotrexate, doxorubicin, cisplatin, ifosfamide, and etoposide [4]. In the most recent decade, the 5-year overall survival reached 65.9% and 80.4% in older children and adolescents (10–24 years) and youngest children (0–10 years), respectively [5]. However, in the age group 10–24 years, which comprises 50% of the total cases, survival has plateaued. The prognostic factors of osteosarcoma include age, sex, tumor size and location, resectability, histological type, response to neoadjuvant chemotherapy, therapeutic regimen, and metastatic disease at diagnosis [6].

In the present article, we aimed to evaluate the factors that impact the prognosis of children and adolescents with osteosarcoma by analyzing records of the Greek Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) during the period 2010–2021, along with a systematic review and meta-analysis of the available literature.