Osteosarcoma is the most common form of primary bone cancer found in children, adolescents, and young adults. This aggressive malignancy originates in the bone, typically forming in the long bones of the arms and legs, often around the knee. Treating osteosarcoma requires a coordinated, multi-modal approach involving a specialized medical team. This strategy combines systemic drug therapy and localized tumor removal.
Systemic Treatment with Chemotherapy
Chemotherapy is a fundamental part of the overall treatment plan, addressing the disease throughout the body. Systemic drugs are used to eliminate cancer cells circulating in the bloodstream (micrometastases) and to reduce the size of the main tumor before surgery.
The initial phase, known as neoadjuvant chemotherapy, is administered before the surgical procedure. This pre-operative therapy aims to shrink the tumor, allowing for a less extensive operation and increasing the chances of successfully saving the affected limb. It also assesses how sensitive the tumor is to the specific chemotherapy drugs being used.
The standard and most widely used chemotherapy regimen often includes a combination of several potent agents, such as high-dose Methotrexate, Doxorubicin, and Cisplatin, frequently referred to as the MAP regimen. After the tumor is surgically removed, adjuvant chemotherapy follows to target any remaining microscopic cancer cells. The post-operative regimen may be adjusted based on the tumor’s response to the initial neoadjuvant phase, ensuring the most effective course of treatment is delivered.
Local Control Through Surgical Intervention
Surgical removal of the tumor is a definitive component of local disease control, typically performed after the initial course of chemotherapy. The primary objective is to remove the entire cancerous section of bone and surrounding tissue with a clear margin, while preserving limb function. Complete removal, known as wide or en bloc resection, is crucial for preventing the cancer from returning at the original site.
Limb-sparing surgery is the preferred method today, replacing the historical reliance on amputation. This intricate operation involves resecting the tumor-bearing bone and reconstructing the limb. Reconstruction uses either a metal endoprosthesis (an internal implant) or a bone graft taken from another part of the body or a donor. Limb-sparing surgery allows the patient to maintain the majority of their limb’s structure, offering a better long-term functional outcome.
Amputation remains necessary if the tumor is too large, involves critical nerves and blood vessels, or if complications make reconstruction unsafe. Following resection, pathologists examine the specimen to determine tumor necrosis (cancer cell death). A high rate of tumor necrosis, often 90% or more, indicates effective neoadjuvant chemotherapy and correlates with a better overall prognosis, guiding the planning of post-operative chemotherapy.
Adjunctive and Specialized Therapies
While chemotherapy and surgery form the backbone of treatment, other specialized therapies are used in specific clinical situations. Osteosarcoma is generally considered radioresistant, meaning it does not respond well to conventional radiation therapy. Consequently, radiation is not typically used as a primary treatment for the main tumor when surgical removal is an option.
Radiation therapy becomes a viable option when the tumor is located in an area where surgery is impossible or would cause unacceptable damage, such as in the spine or pelvis. It is also used to treat sites where the cancer has spread, like the lungs. Newer, highly focused techniques such as proton beam therapy or stereotactic body radiation therapy (SBRT) deliver high doses of radiation precisely to the tumor while minimizing damage to nearby structures.
Emerging Drug Therapies
The drug mifamurtide, an agent that activates the body’s immune cells, has been approved in some regions for use alongside chemotherapy in high-grade, non-metastatic osteosarcoma to potentially improve overall survival. Targeted therapies and immunotherapies represent an emerging area of research, particularly for recurrent or refractory disease. Drugs like cabozantinib and lenvatinib are being investigated in clinical trials. Efforts to explore immune checkpoint inhibitors and CAR T-cell therapies are underway, although these strategies are not yet widely adopted as standard care.
Follow-Up and Long-Term Survivorship
Once the intensive acute treatment phase is completed, the focus shifts to long-term monitoring and rehabilitation. Regular surveillance is implemented to watch for signs of recurrence, which most commonly occurs in the lungs. This protocol involves frequent physical examinations, blood tests, and imaging scans, particularly chest X-rays or computed tomography (CT) scans, performed at regular intervals over several years.
Physical rehabilitation is necessary for patients who have undergone limb-sparing surgery, requiring dedicated physical therapy to regain strength, mobility, and function. Managing potential long-term side effects from the aggressive treatment is a priority in survivorship care. Chemotherapy agents like Doxorubicin can lead to cardiac issues (cardiotoxicity), while Cisplatin can cause hearing loss (ototoxicity) or kidney damage (nephrotoxicity).
Survivors require ongoing monitoring through specialized tests, such as echocardiograms to check heart function and audiograms to test hearing, sometimes for decades after treatment. There is also an elevated risk of developing a second cancer later in life due to the initial chemotherapy or radiation exposure. Comprehensive survivorship care plans address these ongoing health concerns, focusing on maintaining the highest possible quality of life and functional independence.