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Osteosarcoma [OS-tee-oh-sar-KO-muh] is the most common type of bone cancer in children and adolescents, although cancer in young people is rare in general. Osteosarcoma is most common between the ages of 10 and 25 when the bones are rapidly growing. In the US 400 new cases of osteosarcoma are diagnosed per year. Osteosarcoma is potentially curable by combining chemotherapy (medications that kill cancer cells) with surgical removal of the tumor.

• What is Osteosarcoma?
• What are the risk factors for Osteosarcoma?
• What do we know about the biology of osteosarcoama?
• How is Osteosarcoma diagnosed?
• How is Osteosarcoma treated?
• What is the prognosis for survival?
• Can Osteosarcoma come back?

What is Osteosarcoma?

Osteosarcoma is the most common bone cancer in children and adolescents, and the third most common cancer in adolescence. Not all bone cancers are osteosarcomas. Osteosarcoma is a bone tumor that can occur in any bone, but most frequently occurs in the long bones of the arms and legs near the growth plates. The most common sites are the thigh bone above the knee, the shin bone below the knee, and the upper arm bone. Other tumor locations are the skull or jaw and hip bones. At the time of diagnosis 15-20% of patients have detectable metastases that have spread to the lungs or other bones. Metastases are collections of cancerous cells that have spread and are growing at a location different from the original tumor site.

In the US 400 new cases of osteosarcoma are diagnosed per year. Most diagnoses are made during adolescence, between ages 10 and 19, and rarely in young children below five years of age. Osteosarcoma occurs more frequently in males than females.

What are the risk factors for Osteosarcoma?

The exact cause of osteosarcoma is unknown and cannot be prevented because it is associated with random genetic mutations or changes of the bone forming cells (oteoblasts). However, risk factors (things that increase the chance of getting cancer) may exist. It is rare, but several diseases can be passed down from grandparents to parents to children that make the individual, and in some cases other family members, more likely to develop many types of cancer, including osteosarcoma. These diseases include retinoblastoma, Li Fraumeni syndrome, Rothmund-Thomson syndrome, Paget's disease, and Werner's syndrome. The only known environmental risk factor is exposure to radiation, as in previous radiation therapy for some other type of cancer.
More information about these diseases .

What do we know about the biology of osteosarcoama?

Osteosarcoma biology remains a challenge to researchers all over the world. It is not yet well understood what specifically causes a normal bone cell to become a cancer cell. The chromosomes in osteosarcoma cells have complex abnormalities that are different in each tumor. Due to these changes errors occur in important sequences of events, called "pathways", which control normal cell growth and also tumor cell growth. Important pathways controlled by the RB and p53 genes for example lose their ability to control cell growth which is a major step in the process leading to cancer.

Understanding the differences between normal bone cells and osteosarcoma cells has been a high priority in recent osteosarcoma research, with the goal of designing drugs that specifically attack the cancer cells and leave the normal cells alone. In addition to much needed improvements in therapeutic agents, an understanding of the biology of osteosarcoma is also needed to develop better ways to predict and follow the response of each individual's tumor to chemotherapy. This would allow treatment to be customized and individualized to each person for the best possible treatment for their particular cancer.

More information about the biology of osteosarcoma and current research.

What Are Symptoms of Osteosarcoma?

Common signs of osteosarcoma include pain or swelling in or around bones that does not go away. These symptoms might be worse at night or when exercising.

It is important to realize that pain and swelling in arms and legs are common in young people. They result more often from sport injuries than osteosarcoma. However, if pain or swelling in bones persists, a doctor needs to be seen.

How is Osteosarcoma Diagnosed?

Imaging studies are performed first to scan the body for possible osteosarcomas. First an x-ray is taken of the site where symptoms are occurring. This is followed by a CT scan and/or MRI scan to determine the extent of the tumor and to look for skip metastases (more than one tumor site in the same bone). A helical CT scan of the chest and radionucleotide bone scan of the entire body are used to search for sites to which the cancer may have spread. Abnormal areas found on the bone scan should be imaged subsequently using CT scan or MRI.

Biopsy is the best method to diagnose osteosarcoma after the initial imaging studies have been performed. Biopsy allows for identification of cancerous cells under the microscope. It is recommended that biopsies be performed by the surgeon who will perform the operation to remove the osteosarcoma. Once the osteosarcoma has been confirmed by the biopsy, chemotherapy is begun to try to shrink the tumor before surgically removing it.

Once the diagnosis of osteosarcoma has been confirmed by a pathologist, the oncologist will evaluate the results and assign a stage to the tumor. Staging means assessing the progress of the tumor, which helps determine how aggressive the cancer is, whether it has spread, and if so, how extensive it is. Localized low-grade tumors are stage I, localized high-grade tumors are stage II, and metastatic tumors are all stage III. Stages I and II are subdivided into categories A (intracompartmental) and B (extracompartmental).

This is based on the Musculoskeletal Tumor Society Staging system, described by Wolf and Enneking, Orthop Clin North Am 27:473-481, as given in the latest World Health Organization publication on soft tissue and bone pathology and genetics.  Stage III lesions cannot be A, because by definition they have extended out of the primary site's "compartment".

How is Osteosarcoma Treated?

Osteosarcoma treatment has progressed greatly over the past thirty years. The standard treatment for patients with conventional osteosarcoma consists of the combination of chemotherapy and surgery, and in some cases radiation.

Chemotherapy

Osteosarcoma is best treated with chemotherapy before and after surgical removal of the tumor to attempt to prevent or control potential metastases (spread of the tumor). Most patients (80%) at the time of diagnosis have sites of metastasis called micrometastases that are undetectable by standard imaging techniques. This is the basis for using chemotherapy prior to surgery. The chemotherapy drugs most active in osteosarcoma are Doxorubicin, Cisplatin, high-dose methotrexate, ifosfamide, and etoposide. While administration of chemotherapy prior to surgery delays surgery by about three months, it has several advantages. It shrinks the tumor which facilitates subsequent surgical removal of the tissue, and also allows for assessment of how much of the cancer is killed by the treatment (tumor necrosis) at the time of resection. This gives the oncologist valuable insight into the behavior of the individual tumor in response to the drugs that are supposed to kill it. If greater than 90% of the cancer tissue dies due to chemotherapy, it is considered a good response to chemotherapy.

While chemotherapy before surgery helps control the spread of the tumor, chemotherapy after surgery is also critical in order to treat potential tumor sites that were not removed completely by surgery or were undetectable at the time. The most successful treatments combine chemotherapy before and after surgical removal of the tumor.
More about specific chemotherapy drugs.

Clinical trials offer the most up-to-date chemotherapy treatments with the best-known results for improvement or cure of osteosarcoma. The majority of young cancer patients decide to enter into a Phase III clinical trial.
More about the newest clinical trials .

Surgery

If a cure is to be achieved, surgical removal of all the tumor tissue at any site should always be attempted. Most commonly, this is done after a period of chemotherapy. The main goal of surgery is to safely and completely remove the tumor. For those with lung metastases, a thoracotomy with manual exploration of both lungs is recommended, while thoracoscopic techniques are discouraged. At the time of surgery to remove the tumor, reconstructive surgery can take place if needed.

Reconstructive surgical procedures fall into three basic categories:

• Limb salvage: involves removing the tumor and some healthy tissue surrounding it, while preserving blood and nerve supply to keep the limb intact.
• Amputation: involves removal of the limb and enough healthy tissue to ensure that no cancer cells remain.
• Rotationplasty: a compromise between limb salvage and amputation most commonly used for osteosarcomas of the thigh bone (femur).

More information on surgical treatments.

The orthopedic surgeon is extremely important in the care of patients with osteosarcoma to perform the initial biopsy as well as the tumor removal. A study by the Cooperative Osteosarcoma Study Group concluded that incomplete surgery was the most important factor in a negative prognosis for osteosarcoma. Surgery should be conducted only in collaboration with a pediatric oncologist familiar with ongoing clinical trials (studies that test the effectiveness of therapies) to determine the best course of treatment. The majority of young cancer patients decide to enter into a Phase III clinical trial. Clinical trials offer the most up-to-date treatments with the best-known results for improvement or cure of osteosarcoma.

Radiation

As stated above complete surgery is the treatment of choice for osteosarcoma. In selected cases, however, radiotherapy has proven helpful. For example, when the tumor is unable to be removed due to its location or the risk involved, radiation becomes the best treatment option.
More information on radiation treatments .

After Treatment

Osteosarcoma survivors require close follow-up care because side effects of chemotherapy may develop months or years after treatment. After completing chemotherapy, regular blood work and radiographic scans must be continued on an outpatient basis with decreasing frequency over time. Generally, these visits occur every 2-3 months for the first year, every 6 months for the second year and possibly third year, as well as once a year thereafter. Long-term follow-up (five or more years post-therapy) should be annual in a late-effects clinic, with appropriate studies to check for potential late effects of the chemotherapeutic agents used. Visits may include hormonal, cardiologic, reproductive, renal, orthopedic, or auditory evaluations.

What is the prognosis for survival?

With current treatment regimens combining chemotherapy and surgery, osteosarcoma patients without detectable metastases have a survival rate that approaches 70%. Factors that seem to negatively impact prognosis include:

• Presence of metastases (tumor tissue that has migrated to the lungs or other bones)
  • Patients with lung metastases that are removable at diagnosis have about a 30-50% survival rate
  • Patients with lung metastases that are unable to be removed at diagnosis, multiple bone tumors, or cancer that is unresponsive to chemotherapy have a poor prognosis
• Large tumor size
• Poor response to chemotherapy (less than 90% of the cancer tissue had died)

In a recent Italian study, patients whose tumors did not respond well to chemotherapy before surgery were treated with a more intensive longer-term therapy and had a similar outcome to those with a favorable initial response, suggesting that adaptive therapy may be beneficial.

Can Osteosarcoma come back?

Recurrence of osteosarcoma is the most common cause of treatment failure. The lung is the most common site for osteosarcoma to recur, for which a thoracotomy with removal of all palpable lesions is recommended. As in primary disease, complete surgical removal of all detectable lesions is necessary for a cure. Multiple studies have shown that sometimes several repeated resections might be necessary.

In select relapses chemotherapy should be used before and after surgery. The choice of chemotherapy depends on many factors, including the prior therapy used. For example, five courses of Ifosfamide and Etoposide can be used for patients who have not previously received this combination. The combination of Carboplatinum and Etoposide is favored by the German-Austrian-Swiss Cooperative Osteosarcoma Study Group. Due to the many factors influencing the decision, the choice of treatment must be made on an individual basis. Radiation therapy is recommended for inoperable sites or those that were only partly resectable. Often Phase II clinical trials are recommended for patients to try new therapies.

Written and reviewed by: Susanne Ragg, MD, PhD; Deannie Lee, MD, PhD; James Hill, MD; Joseph Bidwell, PhD; Ann Haddix, RN, MSN, CPNP; Jada Paine, MS; Amber MacMahon, BS; Julie Haydon, BS; Michelle Lucke, MPH; Eve Doucette, BS; Elaine Skopelja, MALS, AHIP; Kellie Kaneshiro, AMLS, AHIP. Date last reviewed: August 2006.