Sarcoma Treatment by Stage and Type

Sarcoma is unusual in how little the stage number does.

NCI puts it plainly. Staging here is primarily a research tool. It does not routinely drive decisions. Four other things do that work: the subtype, the grade, where the tumour sits, and whether it has spread.

The reason is variety. Soft tissue sarcoma is not one cancer. It is dozens. They start in fat, muscle, nerve, blood vessel and other tissue. Two tumours can share a stage and act nothing alike.

So the first three questions are: what subtype, what grade, and where.

This page explains what each of those changes. It is not advice about your own treatment.

The AJCC system uses the French FNCLCC grade. It is built from three separate scores, added together.

• How much the tumour still looks like normal tissue. This scores 1 to 3. A 1 means it looks close to normal. A 3 covers the least normal-looking types.
• How fast the cells divide. This scores 1 to 3. It counts dividing cells in the sample.
• How much dead tissue there is. This scores 0 to 2. None scores 0. Under half scores 1. Half or more scores 2.

The total sets the grade. A 2 or 3 is G1. A 4 or 5 is G2. A 6, 7 or 8 is G3.

NCI is clear about why this exists. The score is meant to predict who will spread. That in turn shows who might gain from chemotherapy after surgery.

If your report gives a grade, it is fair to ask which of the three scores drove it.

What this page covers. The evidence here comes from NCI's summary on adult soft-tissue sarcoma. Sarcoma is more than fifty distinct diseases, and several of them sit outside this page: bone sarcomas such as osteosarcoma and Ewing sarcoma, gastrointestinal stromal tumours, Kaposi sarcoma, uterine sarcomas, and the sarcomas of childhood all have their own staging and their own treatment pathways. Match anything below against your named histologic subtype before assuming it applies.

Surgery is the mainstay. For tumours of the arms and legs, NCI calls wide-margin surgery that spares function the cornerstone of care.

The details differ by site.

In the arms and legs, the limb can usually be kept, even in high-grade disease. Surgery is paired with radiation to do it. Plastic surgery to close the gap often allows a wider margin than simply sewing the wound shut. Cutting into the tumour, or shelling it out whole, raises the risk that it comes back.

At the back of the abdomen, the goal is to take out all the disease the eye can see. Organs the tumour has not reached are left alone. NCI says the outlook is worse here. Full removal is harder, and high radiation doses harm nearby organs.

Amputation is now uncommon. In one series of 649 people, 92 lost a limb and 557 kept theirs. Those who lost a limb had large high-grade tumours wrapped around big blood vessels or nerves.

Small low-grade tumours may need surgery alone. NCI describes this for low-grade tumours of the limb or outer trunk. They must be 5 cm or smaller with clear margins. Local control is then about 90 percent.

Radiation lowers the chance of the sarcoma returning where it started. Which side of surgery it goes on is a genuine decision.

The case for adding it is strong. One randomised trial followed 141 people who kept the limb. Among the 70 who had radiation, 1 cancer came back at the same site. Among the 71 who did not, 17 did.

For sarcoma at the back of the abdomen, older records support adding radiation. In a matched review, median survival was 89 months with radiation after surgery and 64 months without. It was 110 months with radiation before surgery and 66 months without. These were not randomised trials.

An implanted radiation source is another option. In a trial of 164 people, the cancer came back at the same site in 18 percent with an implant and 31 percent without, at five years. Only high-grade tumours gained.

This is one of the least settled questions in sarcoma, and NCI does not pretend otherwise.

One review pooled 18 randomised trials. Adding any chemotherapy cut deaths by 6 percent in absolute terms. Adding doxorubicin with ifosfamide cut them by 11 percent. That was a drop from 41 percent to 30 percent.

A later trial of 351 people used the same two drugs after surgery. It did not show the same gain. NCI notes the earlier trials were mostly small. They used different drugs and doses, and mixed different sites and grades.

So this is a conversation, not a rule. Ask what the gain would be for your own subtype and grade. Ask what it would cost you, now and later.

For stage IV disease NCI lists chemotherapy, histology-specific targeted or immunotherapy treatment, and surgery.

Doxorubicin has been the standard for decades. NCI lists other drugs that work: ifosfamide, epirubicin, liposomal doxorubicin, gemcitabine, trabectedin, eribulin, pazopanib, dacarbazine and taxanes. Combining them raises side effects, and in several trials of advanced disease it has not lengthened survival, so single drugs given in sequence are a common approach. That is not a rule. Combinations are still used where the aim is to shrink a tumor quickly — heavy symptoms, disease moving fast, or an attempt to make surgery possible — and how well a sarcoma responds to any of these drugs depends heavily on its histology. Bone sarcomas, GIST and the sarcomas of childhood follow separate pathways altogether.

Leiomyosarcoma is an exception. In the LMS-04 trial, doxorubicin plus trabectedin gave a median survival of 33 months. Doxorubicin alone gave 24 months. But serious side effects hit 97 percent on the pair and 56 percent on the single drug.

Some subtypes do better on one specific drug than on standard chemotherapy. NCI lists these:

• Alveolar soft-part sarcoma: sunitinib or pazopanib, and immunotherapy with atezolizumab or pembrolizumab.
• Angiosarcoma: taxanes.
• Dermatofibrosarcoma protuberans: imatinib.
• Inflammatory myofibroblastic tumour: ALK inhibitors.
• PEComa: mTOR inhibitors, including nab-sirolimus.
• Sarcomas with an NTRK fusion: larotrectinib.

Two of those have a matching FDA label. Atezolizumab is approved for alveolar soft-part sarcoma that cannot be removed or has spread, in adults and children aged 2 and over. Imatinib is approved for dermatofibrosarcoma protuberans that cannot be removed, has come back, or has spread.

Three more drugs are approved after earlier chemotherapy. Each label is narrower than the words soft tissue sarcoma suggest. Trabectedin covers liposarcoma or leiomyosarcoma after an anthracycline drug. Eribulin covers liposarcoma only, again after an anthracycline. Pazopanib covers advanced soft tissue sarcoma after chemotherapy. Its label adds that it has not been shown to work in fatty tumours or in GIST.

This is why the exact subtype on your pathology report matters so much.

SEER reports five-year relative survival of 65.7 percent for soft tissue cancer for 2016 through 2022. By stage at diagnosis it is 83.3 percent for localised, 58.2 percent for regional and 17.0 percent for distant disease.

Those figures average a very wide family. A low-grade fatty tumour in the thigh is in there. So is a high-grade tumour at the back of the abdomen. Ask what the picture looks like for your own subtype and grade.

• Call 911 or go to an emergency department if a limb becomes cold or pale, or suddenly severely painful, or you lose movement in it.
• Call 911 or go to an emergency department if you cough up blood or become suddenly short of breath. The lung is the usual site of spread for soft tissue sarcoma.
• Call your care team at once, whatever the hour, if you have a temperature of 100.4°F (38°C) or higher during chemotherapy, or chills. The CDC describes fever during chemotherapy as a medical emergency because low white cells let an infection spread fast. If they cannot be reached within minutes, go to an emergency department and say you are on chemotherapy.
• Call your care team the same day if a surgical wound is opening, leaking, or newly red and painful.
• Call your care team the same day if you notice new numbness or weakness in a limb.
• Call your care team within a day or two if a lump is growing noticeably over days.

Soft Tissue Sarcoma, Newly Diagnosed With Sarcoma, What Does High Grade Mean?, and Getting a Second Opinion.

• https://www.cancer.gov/types/soft-tissue-sarcoma/hp/adult-soft-tissue-treatment-pdq
• https://seer.cancer.gov/statfacts/html/soft.html
• https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6fa682c9-a312-4932-9831-f286908660ee
• https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=211ef2da-2868-4a77-8055-1cb2cd78e24b
• https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=472bd78e-be17-4b9d-90f4-9482c3aec9ff
• https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eeaaaf38-fb86-4d9f-a19d-0f61daac2fd7
• https://www.cancer.gov/about-cancer/treatment/side-effects/infection