Osteosarcoma is a cancer in which tumor cells produce an abnormal bone matrix called osteoid. It primarily affects adolescents and young adults, with a slight predominance among males. In France, approximately 100 to 150 new cases are diagnosed each year.

More than half of pediatric osteosarcomas occur in the long bones near the knee, primarily the lower end of the femur or the upper end of the tibia. Other bones may be affected, including the humerus, pelvis, or jaw.

Persistent pain is the most common symptom. It may occur at night, worsen gradually, or initially be attributed to an injury or physical activity.

Imaging

An X-ray of the painful area is often the first test performed. An MRI provides detailed information on the extent of the lesion within the bone and surrounding tissues, as well as its relationship to the joint, blood vessels, and nerves. A chest CT scan is performed to check for lung metastases. A PET-CT scan or a bone scan completes the follow-up evaluation according to the protocol.

Biopsy

A biopsy confirms the diagnosis and determines the type and grade of the osteosarcoma. It must be performed after imaging, at a specialized center, using a biopsy site that can be removed during definitive surgery.

Staging

At diagnosis, metastatic disease is present in a minority of patients. The lungs are the most common site, followed by other bones. The evaluation also assesses the feasibility of complete resection of the primary tumor and all visible metastases.

The main factors are the presence of metastases, the possibility of complete surgical resection, the tumor’s location, and the histological response to chemotherapy. After surgery, the pathologist measures the proportion of tumor cells that have been destroyed. Necrosis of 90% or more is typically considered a good histological response.

For high-grade osteosarcoma, treatment combines chemotherapy and complete surgery. The schedule and medications vary depending on the patient’s age, the treatment protocol, the tumor’s location, and any previous treatments received.

Chemotherapy Before Surgery

Initial chemotherapy treats tumor cells that may have spread at an early stage and helps assess the tumor’s sensitivity to treatment. International treatment regimens often rely on a combination of high-dose methotrexate, doxorubicin, and cisplatin, known as MAP. Other combinations may be used depending on the patient’s age and the protocol followed in France.

Surgery

Surgery is the key factor in local control. The goal is complete resection with clear margins. Limb-sparing surgery with reconstruction is possible in the vast majority of osteosarcomas of the limbs. Amputation is sometimes necessary when limb-sparing surgery would not allow for either complete excision or satisfactory function.

Chemotherapy After Surgery

Chemotherapy resumes after surgery to complete systemic treatment. The histological response provides important prognostic information; however, the routine addition of other drugs in poor responders has not, on its own, demonstrated sufficient improvement to be considered a universal rule.

The strategy combines chemotherapy with surgical resection of the primary tumor and, whenever feasible, of all metastases. The possibility of complete resection of pulmonary or bone metastases is a key factor in the decision-making process.

When not all lesions can be removed, the case is discussed at a specialized center. High-precision radiation therapy or interventional radiology techniques may be considered in certain situations, but they do not systematically replace surgery.

Relapses most often occur in the lungs, but can also be bone or local. Complete surgical resection of all accessible lesions is often the most important treatment when feasible. Interventional radiology may be considered for certain selected pulmonary or bone metastases.

Chemotherapy depends on the time to relapse, the number of lesions, and the medications already received. Amputation is not an automatic consequence of a local recurrence: the strategy must be evaluated on a case-by-case basis by a specialized team. Clinical trials may be offered.

The European Phase III FOSTER-CabOs trial, coordinated by Dr. Nathalie Gaspar at Gustave Roussy, aims to evaluate maintenance therapy with cabozantinib following first-line treatment, compared to a watch-and-wait strategy, to study its effect on event-free survival and quality of life.

The program also includes biological studies of tumor and blood samples to identify biomarkers. The trial’s enrollment status and inclusion criteria should be verified at the time of this publication, as they are subject to change based on regulatory approvals and the activation of participating centers.

Follow-up care is designed to monitor for recurrence and support functional recovery. It depends on the location of the tumor, the type of surgery performed, the medications prescribed, and any complications that have arisen.

Gustave Roussy is one of the coordinating centers of the national NETSARC+ network. Diagnosis and treatment strategies are discussed during sarcoma multidisciplinary team (MDT) meetings, with pediatric or adolescent/young adult (AJA) coordination for the youngest patients. Certain complex bone surgeries are organized in collaboration with expert partner institutions.

The care pathway combines, as needed, pediatric or medical oncology, surgery, radiation therapy, imaging, pathology, rehabilitation, pain management, psychological support, educational services, adapted physical activity, and social support.