Stages and Prognostic Markers of Osteosarcoma

Once osteosarcoma is diagnosed, doctors need to assess how big the tumor is and where it has spread. This is known as the stage of the cancer. Prognostic factors are features of people and tumors that may predict who will respond best to treatment. These tools cannot tell you for sure if treatment will be successful, but they may help give you a better understanding of how likely this is.

Staging systems

For osteosarcoma, there are a few staging systems used.

The stage of an osteosarcoma is based on the results of a physical exam, imaging tests, and any biopsies that have been done, which are described in Tests for Osteosarcoma.

Localized versus metastatic

For treatment, osteosarcoma tumors are described and treated based on whether they are localized in one place or metastatic, meaning they have spread to other parts of the body.

Musculoskeletal Tumor Society (MSTS) staging system

One system used to stage osteosarcoma is the MSTS system, also known as the Enneking system. It is based on 3 key pieces of information:

• The grade (G) of the tumor, which is a measure of how likely it is to grow and spread, based on how it looks under the microscope. Tumors are either low-grade cancers (G1) or high-grade cancers (G2). Low-grade tumor cells look more like normal cells and are less likely to grow and spread quickly, while high-grade tumor cells look more abnormal.
• The extent of the primary tumor (T), which is classified as either intracompartmental (T1), meaning it has stayed within or near the bone, or extracompartmental (T2), meaning it has extended beyond the bone into other nearby structures.
• If the tumor has metastasized (M), which means it has spread to other areas, either to nearby lymph nodes (bean-sized collections of immune system cells) or other organs. Tumors that have not spread to the lymph nodes or other organs are considered M0, while those that have spread are M1.

These factors are combined to give an overall stage, using Roman numerals from I to III. Stages I and II are divided into A for intracompartmental tumors or B for extracompartmental tumors.

Stage	Grade	Tumor	Metastasis
IA	G1	T1	M0
IB	G1	T2	M0
IIA	G2	T1	M0
IIB	G2	T2	M0
III	G1 or G2	T1 or T2	M1

In summary:

• Low-grade, localized tumors are stage I.
• High-grade, localized tumors are stage II.
• Metastatic tumors (regardless of grade) are stage III.

The TNM staging system

Another system sometimes used to stage bone cancers (including osteosarcomas) is the American Joint Commission on Cancer (AJCC) TNM system. This system is based on 4 key pieces of information:

• T describes the size of the main (primary) tumor and if it appears in more than one spot in the bones.
• N describes the extent of spread to nearby (regional) lymph nodes. Bone tumors rarely spread to the lymph nodes.
• M indicates if the cancer has metastasized (spread) to other organs of the body. The most common sites of spread are the lungs or other bones.
• G stands for the grade of the tumor, which describes how the cancer cells look under a microscope. Low-grade tumor cells look more like normal cells and are less likely to grow and spread quickly, while high-grade tumor cells look more abnormal.

Numbers after T, N, M, and G give more details about each of these factors.

Once the T, N, and M categories and the grade of osteosarcoma have been determined, the information is combined into an overall stage. These stages (which are different from those of the MSTS system) are described using Roman numerals from I to IV (1 to 4) and are sometimes divided further.

Osteosarcoma staging can be confusing. If you have any questions about the stage of the cancer, ask a member of the cancer care team to explain it to you in a way you understand.

Prognostic factors

In people with cancer, certain factors that can affect outlook (prognosis) are called prognostic factors. They help doctors anticipate how a cancer will respond to different treatments and help them decide how intense treatment should be. Factors that may be associated with outlook in osteosarcoma include:

• Metastases: Tumors that have spread outside of the bones, or metastasized, can be more difficult to treat.
• Site of the main tumor: Tumors that arise from the bones of the arms or legs often have a better outlook than those in the pelvis or spine. Having surgery that completely removes the main tumor improves the chance of cure.
• Size of the main tumor: Smaller tumors are easier to surgically remove than larger tumors.
• How well the cancer responds to chemotherapy before surgery: When osteosarcoma tumors are removed by surgeons, specialized doctors look at the tumor under the microscope. When more than 90% of the tumor cells have died after early chemotherapy, the cancer is less likely to recur later.
• How quickly chemotherapy can be started after surgery: Studies have found that delaying restarting chemotherapy for more than 3 weeks after surgery can impact prognosis. For this reason, doctors will often restart chemotherapy as soon as it is safe to do so after surgery.
• Sex: Women with osteosarcoma have a slightly higher chance of being cured than men.
• Age at diagnosis: Young adults aged 18–40 tend to have a slightly worse prognosis than children and teens with osteosarcoma.
• LDH and alkaline phosphatase: At diagnosis, people with lower laboratory results for LDH and alkaline phosphatase tend to have smaller tumors and ones that have not metastasized.