Osteosarcoma is a rare form of bone cancer that originates in the cells that form bone tissue, most commonly affecting adolescents and young adults. This malignancy typically develops in the long bones of the arms and legs, often near the knee joint. Treatment is complex and requires a multi-modal approach combining systemic therapy and local control. The standard strategy involves sequential therapies: drug treatment, followed by surgery, and then additional drug treatment.
How Treatment Plans Are Determined
Developing a strategy to treat osteosarcoma is a highly individualized process based on a comprehensive assessment of the disease. Decisions are made by a multidisciplinary team that includes surgical, medical, and radiation oncologists. The goal is to eliminate the tumor while preserving the greatest amount of function and quality of life.
The foundation of the treatment plan rests on accurately classifying the extent and nature of the tumor through staging. This involves detailed imaging, such as X-rays, Magnetic Resonance Imaging (MRI), and Computed Tomography (CT) scans, to define the tumor’s size and local spread. A biopsy provides the tissue sample necessary for diagnosis and determines the tumor’s grade, which measures how aggressive the cancer cells appear under a microscope.
Two primary factors guide the decision-making process: the tumor’s location and whether the cancer has metastasized (spread) to distant parts of the body. Although most osteosarcomas appear localized initially, many patients have microscopic spread, most commonly to the lungs, which necessitates systemic therapy. Tumors located in difficult-to-access areas like the pelvis or spine may require different surgical considerations than those in the limbs. Staging systems, such as the Musculoskeletal Tumor Society (MSTS) system, classify tumors based on their grade, location, and presence of metastasis to determine the best path forward.
Chemotherapy: Preparing for and Following Surgery
Systemic drug treatment, known as chemotherapy, is a cornerstone of osteosarcoma management, administered both before and after surgical removal of the tumor. This strategy is necessary because, even when the cancer appears localized, there is a high likelihood of unseen cancer cells (micrometastases) having already spread through the bloodstream. Chemotherapy has significantly improved survival rates compared to surgery alone.
Chemotherapy given before surgery is known as neoadjuvant chemotherapy. This initial phase serves two primary purposes: shrinking the tumor to make surgical removal easier and potentially increase the chances of a successful limb-sparing procedure, and eliminating distant micrometastases. Neoadjuvant therapy typically lasts several weeks, often 8 to 12 weeks, before the operation.
The most frequently used drug combination is the MAP regimen, which includes high-dose methotrexate, doxorubicin, and cisplatin. These agents are delivered intravenously in cycles, with rest periods to allow the body to recover. High-dose methotrexate protocols require careful monitoring with rigorous hydration and the administration of leucovorin to protect healthy cells from toxicity. Other potent agents, such as ifosfamide and etoposide, may be added depending on the specific protocol and the patient’s health.
Following surgery, patients receive adjuvant chemotherapy, which continues systemic treatment to eradicate any remaining cancer cells. The histological response—the percentage of tumor tissue killed by the neoadjuvant chemotherapy—is assessed by a pathologist and is a strong predictor of long-term survival. Treatment protocols may be adjusted based on this response, though the effectiveness of changing drugs for patients showing a poor response is a subject of ongoing research. The total duration of chemotherapy, including both pre- and post-operative phases, typically spans several months.
Surgical Removal of the Tumor
Surgery is the local control component of the treatment plan, aiming to physically remove the main tumor mass from the bone. The primary goal is to achieve “wide margins,” meaning the surgeon removes the entire tumor along with a border of healthy, cancer-free tissue. The removed tissue is immediately sent for pathological analysis to confirm that the margins are clear, which indicates a successful local control effort.
The preferred procedure for tumors in the limbs is limb-sparing surgery, which removes the affected section of bone without requiring amputation. This approach is possible due to the effectiveness of neoadjuvant chemotherapy in shrinking the tumor. After the tumor-bearing bone segment is removed, orthopedic surgeons reconstruct the limb, often using a specialized metal implant (endoprosthesis) or a bone graft.
Despite advances in limb preservation, amputation remains necessary if the tumor is very large, involves surrounding nerves and blood vessels, or if a wide margin cannot be safely achieved with limb-sparing techniques. The choice between limb-sparing surgery and amputation balances the necessity of complete tumor removal with the desire to preserve limb function. A successful limb-sparing procedure requires extensive physical therapy and rehabilitation to restore mobility and strength following reconstruction.
Specialized Therapies and Long-Term Monitoring
While chemotherapy and surgery are the mainstays of osteosarcoma treatment, specialized therapies like radiation therapy play a role in specific circumstances. Osteosarcoma cells are relatively resistant to conventional radiation, so it is not used as a primary treatment for tumors that can be surgically removed. Its use is reserved for tumors that are unresectable, meaning they cannot be safely or completely removed due to their location near vital structures.
Radiation therapy may also be employed to control pain in cases of metastatic disease or to treat sites of recurrence. Modern techniques, such as external beam radiation therapy (EBRT), are carefully planned to focus high-energy rays on the tumor site while minimizing damage to surrounding healthy tissues. Emerging therapies, including targeted drugs and immunotherapy, are areas of ongoing research, particularly for patients with recurrent or refractory disease that has not responded to standard protocols.
Following active treatment, a rigorous program of long-term monitoring (surveillance) is implemented to check for recurrence and manage potential late effects of therapy. Recurrence often occurs in the lungs, so regular imaging, such as chest X-rays or CT scans, is a routine part of follow-up care. These visits are frequent in the first few years after treatment and gradually decrease over time.
The chemotherapy and surgery used to treat osteosarcoma can cause long-term health issues that require specialized monitoring. For instance, doxorubicin can cause heart damage (cardiotoxicity), and high-dose methotrexate can affect the kidneys. Regular check-ups include blood tests to monitor organ function and imaging of the heart (echocardiograms) to detect problems early. This comprehensive, long-term follow-up ensures that survivors receive the necessary care to maintain their health and quality of life.