Soft tissue sarcoma is a disease in which malignant (cancer) cells form in the soft tissues of the body.

Soft tissues of the body connect, support, and surround other body parts and organs. The soft tissues of the body include the following:

• A mix of bone and cartilage.
• Fibrous tissue.
• Muscles.
• Tendons (bands of fiber that connect muscles to bones).
• Fat.
• Blood vessels.
• Lymph vessels.
• Nerves.
• Tissues around joints (synovial tissue).

Soft tissue sarcomas can form almost anywhere in the body, including the head, neck, and trunk, but are most common in the arms, legs, abdomen, and retroperitoneum.

There are many types of soft tissue sarcoma. The cells of each type of sarcoma look different under a microscope, based on the type of soft tissue in which the cancer began.

Having certain inherited disorders can increase the risk of soft tissue sarcoma.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn't mean that you will not get cancer. Talk with your doctor if you think you may be at risk. Risk factors for soft tissue sarcoma include the following inherited disorders:

• Li-Fraumeni syndrome (TP53 mutation).
• von Recklinghausen disease (neurofibromatosis type 1; NF1 mutation).
• Gardner syndrome (APC mutation).
• Nevoid basal cell carcinoma syndrome (Gorlin syndrome; PTCH1 mutation).
• Tuberous sclerosis (Bourneville disease; TSC1 or TSC2 mutation).
• Werner syndrome (adult progeria; WRN mutation).

Other risk factors for soft tissue sarcoma include the following:

• Past treatment with radiation therapy.
• Having lymphedema in the arms or legs for a long time.
• Being exposed to certain chemicals, such as Thorotrast (thorium dioxide), vinyl chloride, or arsenic.
• Being infected with HIV and human herpesvirus 8. These viruses have been linked to Kaposi sarcoma.

A sign of soft tissue sarcoma is a lump or swelling in soft tissue of the body.

A sarcoma may appear as a painless lump under the skin, often on an arm or a leg. Sarcomas that begin in the abdomen may not cause signs or symptoms until they get very big. As the sarcoma grows and presses on nearby organs, nerves, muscles, or blood vessels, signs and symptoms may include:

• Pain.
• Trouble breathing.

Other conditions may cause the same signs and symptoms. Check with your doctor if you have any of these problems.

Soft tissue sarcoma is diagnosed with a biopsy.

If your doctor thinks you may have a soft tissue sarcoma, a biopsy will be done. The type of biopsy will be based on the size of the tumor and where it is in the body. These types of biopsies may be used:

• Core needle biopsy: The removal of tissue using a wide needle. Multiple tissue samples are taken. This procedure may be guided using ultrasound, CT scan, or MRI.
• Incisional biopsy: The removal of part of a lump or a sample of tissue. An incisional biopsy may be done when a core needle biopsy is not safe to perform or core needle biopsy findings are not clear.

Careful planning of the biopsy should involve the surgeon, a radiation oncologist, and an interventional radiologist who uses medical imaging to guide diagnosis. Samples will be taken from the primary tumor, lymph nodes, and other suspicious areas. A pathologist views the tissue under a microscope to look for cancer cells and to find out the grade of the tumor. The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the cells are dividing. High-grade tumors usually grow and spread more quickly than low-grade tumors.

Because soft tissue sarcoma can be hard to diagnose, the tissue samples should be checked by a pathologist who has experience in diagnosing soft tissue sarcoma.

The following tests may be done on the tissue that was removed:

• Immunohistochemistry: A laboratory test that uses antibodies to check for certain antigens (markers) in a sample of a patient’s tissue. The antibodies are usually linked to an enzyme or a fluorescent dye. After the antibodies bind to a specific antigen in the tissue sample, the enzyme or dye is activated, and the antigen can then be seen under a microscope. This type of test is used to help diagnose cancer and to help tell one type of cancer from another type of cancer.
• Flow cytometry: A laboratory test that measures the number of cells in a sample, the percentage of live cells in a sample, and certain characteristics of the cells, such as size, shape, and the presence of tumor (or other) markers on the cell surface. The cells from a sample of a patient’s blood, bone marrow, or other tissue are stained with a fluorescent dye, placed in a fluid, and then passed one at a time through a beam of light. The test results are based on how the cells that were stained with the fluorescent dye react to the beam of light.
• Molecular profiling: A laboratory method that uses a sample of tissue, blood, or other body fluid to check for certain genes, proteins, or other molecules that may be a sign of a disease or condition, such as cancer. It can also be used to check for certain changes in a gene or chromosome that may increase a person’s risk of developing cancer or other diseases. It may be done with other procedures, such as biopsies, to help diagnose some types of cancer. It may also be used to help plan treatment, find out how well treatment is working, make a prognosis, or predict whether cancer will come back or spread to other parts of the body.
• Light and electron microscopy: A laboratory test in which cells in a sample of tissue are viewed under regular and high-powered microscopes to look for certain changes in the cells.
• Cytogenetic analysis: A laboratory test in which the chromosomes of cells in a sample of tissue are counted and checked for any changes, such as broken, missing, rearranged, or extra chromosomes. Changes in certain chromosomes may be a sign of cancer. Cytogenetic analysis is used to help diagnose cancer, plan treatment, or find out how well treatment is working.
• FISH (fluorescence in situ hybridization): A laboratory test used to look at and count genes or chromosomes in cells and tissues. Pieces of DNA that contain fluorescent dyes are made in the laboratory and added to a sample of a patient’s cells or tissues. When these dyed pieces of DNA attach to certain genes or areas of chromosomes in the sample, they light up when viewed under a fluorescent microscope. The FISH test is used to help diagnose cancer and help plan treatment.

KEY POINTS

• After soft tissue sarcoma has been diagnosed, tests are done to find out if cancer cells have spread within the soft tissue or to other parts of the body.
• There are three ways that cancer spreads in the body.
• Cancer may spread from where it began to other parts of the body.
• The grade of the tumor is also used to describe the cancer and plan treatment.
• For soft tissue sarcoma of the trunk, arms, and legs, the following stages are used:
  • Stage I
  • Stage II
  • Stage III
  • Stage IV
• For soft tissue sarcoma of the retroperitoneum, the following stages are used:
  • Stage I
  • Stage II
  • Stage III
  • Stage IV
• There is no standard staging system for soft tissue sarcoma of the head, neck, chest, or abdomen.
• Soft tissue sarcoma can recur (come back) after it has been treated.

After soft tissue sarcoma has been diagnosed, tests are done to find out if cancer cells have spread within the soft tissue or to other parts of the body.

The process used to find out if cancer has spread within the soft tissue or to other parts of the body is called staging. Staging of soft tissue sarcoma is also based on the grade and size of the tumor, and whether it has spread to the lymph nodes or other parts of the body. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment.

In addition to asking about your personal and family health history and doing a physical exam, your doctor may perform the following tests and procedures in the staging process:

• Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
• Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease.
• Complete blood count (CBC): A procedure in which a sample of blood is drawn and checked for the following:
  • The number of red blood cells, white blood cells, and platelets.
  • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
  • The portion of the blood sample made up of red blood cells.
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside of the body, such as the lung, abdomen, and pelvis, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

The results of these tests are viewed together with the results of the tumor biopsy to find out the stage of the soft tissue sarcoma before treatment is given. Sometimes chemotherapy or radiation therapy is given as the initial treatment and afterwards the soft tissue sarcoma is staged again.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

• Tissue. The cancer spreads from where it began by growing into nearby areas.
• Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
• Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

• Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
• Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if soft tissue sarcoma spreads to the lung, the cancer cells in the lung are actually soft tissue sarcoma cells. The disease is metastatic soft tissue sarcoma, not lung cancer.

The grade of the tumor is also used to describe the cancer and plan treatment.

The grade of the tumor describes how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Low grade, mid grade, and high grade are used to describe soft tissue sarcoma:

• Low grade: In low-grade soft tissue sarcoma, the cancer cells look more like normal cells under a microscope and grow and spread more slowly than in mid-grade and high-grade soft tissue sarcoma.
• Mid grade: In mid-grade soft tissue sarcoma, the cancer cells look more abnormal under a microscope and grow and spread more quickly than in low-grade soft tissue sarcoma.
• High grade: In high-grade soft tissue sarcoma, the cancer cells look more abnormal under a microscope and grow and spread more quickly than in low-grade and mid-grade soft tissue sarcoma.

For soft tissue sarcoma of the trunk, arms, and legs, the following stages are used:

Stage I

Stage I soft tissue sarcoma of the trunk, arms, and legs is divided into stages IA and IB:

• In stage IA, the tumor is 5 centimeters or smaller and is low grade or the grade is unknown.
• In stage IB, the tumor is larger than 5 centimeters and is low grade or the grade is unknown.

Stage II

In stage II soft tissue sarcoma of the trunk, arms, and legs, the tumor is 5 centimeters or smaller and is mid grade or high grade.

Stage III

Stage III soft tissue sarcoma of the trunk, arms, and legs is divided into stages IIIA and IIIB:

• In stage IIIA, the tumor is larger than 5 centimeters but not larger than 10 centimeters and is mid grade or high grade.
• In stage IIIB, the tumor is larger than 10 centimeters and is mid grade or high grade.

Stage IV

In stage IV soft tissue sarcoma of the trunk, arms, and legs, one of the following is found:

• the tumor is any size, any grade, and has spread to nearby lymph nodes; or
• the tumor is any size, any grade, and may have spread to nearby lymph nodes. Cancer has spread to other parts of the body, such as the lung.

For soft tissue sarcoma of the retroperitoneum, the following stages are used:

Stage I

Stage I soft tissue sarcoma of the retroperitoneum is divided into stages IA and IB:

• In stage IA, the tumor is 5 centimeters or smaller and is low grade or the grade is unknown.
• In stage IB, the tumor is larger than 5 centimeters and is low grade or the grade is unknown.

Stage II

In stage II soft tissue sarcoma of the retroperitoneum, the tumor is 5 centimeters or smaller and is mid grade or high grade.

Stage III

Stage III soft tissue sarcoma of the retroperitoneum is divided into stages IIIA and IIIB:

• In stage IIIA, the tumor is larger than 5 centimeters but not larger than 10 centimeters and is mid grade or high grade.
• In stage IIIB, one of the following is found:
  • the tumor is larger than 10 centimeters and is mid grade or high grade; or
  • the tumor is any size, any grade, and has spread to nearby lymph nodes.

Stage IV

In stage IV soft tissue sarcoma of the retroperitoneum, the tumor is any size, any grade, and may have spread to nearby lymph nodes. Cancer has spread to other parts of the body, such as the lung.

There is no standard staging system for soft tissue sarcoma of the head, neck, chest, or abdomen.

Soft tissue sarcoma can recur (come back) after it has been treated.

The cancer may come back in the same soft tissue or in other parts of the body.

Treatment Option Overview

KEY POINTS

• There are different types of treatment for patients with soft tissue sarcoma.
• Five types of standard treatment are used:
  • Surgery
  • Radiation therapy
  • Chemotherapy
• Targeted therapy
• Immunotherapy
• Treatment for soft tissue sarcoma may cause side effects.
• Patients may want to think about taking part in a clinical trial.
• Patients can enter clinical trials before, during, or after starting their cancer treatment.
• Follow-up tests may be needed.

There are different types of treatment for patients with soft tissue sarcoma.

Different types of treatments are available for patients with soft tissue sarcoma. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Five types of standard treatment are used:

Surgery

Surgery is the most common treatment for soft tissue sarcoma. It may be the only treatment needed for small, low-grade tumors, especially in the trunk, arms, or legs. The following surgical procedures may be used:

• Mohs micrographic surgery: A procedure in which the tumor is cut from the skin in thin layers. During surgery, the edges of the tumor and each layer of tumor removed are viewed through a microscope to check for cancer cells. Layers continue to be removed until no more cancer cells are seen. This type of surgery removes as little normal tissue as possible and is often used where appearance is important, such as on the skin.

• Wide local excision: Removal of the tumor along with some normal tissue around it. For tumors of the head, neck, abdomen, and trunk, as little normal tissue as possible is removed.
• Limb-sparing surgery: Removal of the tumor in an arm or leg without amputation, so the use and appearance of the limb is saved. Radiation therapy or chemotherapy may be given first to shrink the tumor. The tumor is then removed in a wide local excision. Tissue and bone that are removed may be replaced with a graft using tissue and bone taken from another part of the patient's body, or with an implant such as artificial bone.
• Amputation: Surgery to remove part or all of an arm or leg. Amputation is rarely used to treat soft tissue sarcoma.
• Lymphadenectomy: A surgical procedure in which lymph nodes are removed and a sample of tissue is checked under a microscope for signs of cancer. This procedure is also called a lymph node dissection.

Radiation therapy or chemotherapy may be given before or after surgery to remove the tumor. When given before surgery, radiation therapy or chemotherapy will make the tumor smaller and reduce the amount of tissue that needs to be removed during surgery. Treatment given before surgery is called neoadjuvant therapy. When given after surgery to remove all of the tumor that can be seen, radiation therapy or chemotherapy will kill any remaining cancer cells. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy:

• External radiation therapy uses a machine outside the body to send radiation toward the area of the body with cancer.
  • Intensity-modulated radiation therapy (IMRT) is a type of 3-dimensional (3-D) radiation therapy that uses a computer to make pictures of the size and shape of the tumor. Thin beams of radiation of different intensities (strengths) are aimed at the tumor from many angles. This type of external radiation therapy causes less damage to nearby healthy tissue and is less likely to cause dry mouth, trouble swallowing, and damage to the skin.
• Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

The way the radiation therapy is given depends on the type and stage of the cancer being treated. External radiation therapy and internal radiation therapy may be used to treat soft tissue sarcoma.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy).

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells. Targeted therapy may cause less harm to normal cells than chemotherapy or radiation therapy do. There are different types of targeted therapy. These include:

• Tyrosine kinase inhibitor therapy: These inhibitors block signals that cancer cells need to grow and divide. Some tyrosine kinase inhibitors also have angiogenesis inhibitor effects. Tyrosine kinase inhibitors used to treat soft tissue sarcoma include pazopanib, imatinib, sunitinib, and regorafenib. New types of tyrosine kinase inhibitors are being studied, including cediranib and larotrectinib.
• Histone methyltransferase inhibitor therapy: This therapy may help keep cancer cells from growing. Tazemetostat is a type of histone methyltransferase inhibitor therapy used to treat soft tissue sarcoma.

Immunotherapy

Immunotherapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This cancer treatment is a type of biologic therapy.

Immune checkpoint inhibitor therapy is a type of immunotherapy. Some types of immune system cells, such as T cells, and some cancer cells have certain proteins, called checkpoint proteins, on their surface that keep immune responses in check. These checkpoints help keep immune responses from being too strong and sometimes can keep T cells from killing cancer cells. When these checkpoints are blocked, T cells can kill cancer cells better.

Types of immune checkpoint inhibitor therapy include the following:

• CTLA-4 inhibitor therapy: CTLA-4 is a protein on the surface of T cells that helps keep the body's immune responses in check. When CTLA-4 attaches to another protein called B7 on a cancer cell, it stops the T cell from killing the cancer cell. CTLA-4 inhibitors attach to CTLA-4 and allow the T cells to kill cancer cells.

  Ipilimumab is a type of CTLA-4 inhibitor that is being studied to treat soft tissue sarcoma.

• PD-1 and PD-L1 inhibitor therapy: PD-1 is a protein on the surface of T cells that helps keep the body's immune responses in check. PD-L1 is a protein found on some types of cancer cells. When PD-1 attaches to PD-L1, it stops the T cell from killing the cancer cell. PD-1 and PD-L1 inhibitors keep PD-1 and PD-L1 proteins from attaching to each other. This allows the T cells to kill cancer cells.

  Pembrolizumab and nivolumab are PD-1 inhibitors that are used to treat progressive and recurrent soft tissue sarcoma.

Treatment for soft tissue sarcoma may cause side effects.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. Information about clinical trials supported by NCI can be found on NCI’s clinical trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

Follow-up tests may be needed.

As you go through treatment, you will have follow-up tests or check-ups. Some tests that were done to diagnose or stage the cancer may be repeated to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back).

Treatment of Stage I Soft Tissue Sarcoma

Treatment of stage I soft tissue sarcoma may include the following:

• Surgery to remove the tumor, such as Mohs microsurgery for small sarcomas of the skin, wide local excision, or limb-sparing surgery.
• Radiation therapy before and/or after surgery.
• High-dose radiation therapy, for tumors that cannot be removed by surgery.

Treatment of Stage II Soft Tissue Sarcoma and Stage III Soft Tissue Sarcoma That Has Not Spread to Lymph Nodes

Treatment of stage II soft tissue sarcoma and stage III soft tissue sarcoma that has not spread to lymph nodes may include the following:

• Surgery to remove the tumor, such as wide local excision or limb-sparing surgery.
• Radiation therapy before or after surgery.
• Radiation therapy and/or chemotherapy before limb-sparing surgery. Radiation therapy may also be given after surgery.
• High-dose radiation therapy for tumors that cannot be removed by surgery.

Treatment of Stage III Soft Tissue Sarcoma That Has Spread to Lymph Nodes (Advanced)

Treatment of stage III soft tissue sarcoma that has spread to lymph nodes (advanced) may include the following:

• Surgery (wide local excision) with lymphadenectomy. Radiation therapy may also be given after surgery.
• Surgery with neoadjuvant therapy (chemotherapy or radiation therapy) or adjuvant therapy (radiation therapy).

Treatment of Stage IV Soft Tissue Sarcoma

Treatment of stage IV soft tissue sarcoma may include the following:

• Chemotherapy.
• Surgery to remove cancer that has spread to the lungs.
• Targeted therapy with a tyrosine kinase inhibitor (pazopanib or imatinib).

Treatment of Recurrent Soft Tissue Sarcoma

Treatment of recurrent soft tissue sarcoma may include the following:

• Surgery (wide local excision) with or without radiation therapy.
• Surgery (amputation; rarely done).
• Surgery to remove cancer that has recurred in the lungs.
• Targeted therapy with a tyrosine kinase inhibitor (pazopanib or imatinib).
• Chemotherapy.
• A clinical trial of an immune checkpoint inhibitor (pembrolizumab, nivolumab, or ipilimumab).

Certain factors affect treatment options and prognosis (chance of recovery).

The treatment options and prognosis depend on the following:

• The type of soft tissue sarcoma.
• The size, grade, and stage of the tumor.
• Where the tumor is in the body.
• Whether all of the tumor is removed by surgery.
• The patient's age and general health.
• Whether the cancer has recurred (come back).

Small, low-grade tumors, especially in the trunk, arms, or legs, are frequently treated with surgery alone. High-grade sarcomas are more difficult to treat and more likely to spread.