Soft tissue sarcoma of the extremity (localised and advanced)
Most soft tissue sarcomas arise in an arm or leg. Limb-saving surgery with radiotherapy cures most localised tumours and is as safe as amputation. For spread disease doxorubicin is the backbone: adding ifosfamide shrinks more tumours without lengthening life, and in leiomyosarcoma adding trabectedin doubles the time the disease stays controlled.
Overview
Extremity soft tissue sarcoma is the stage and site framework for the histology-specific records: undifferentiated pleomorphic sarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, myxofibrosarcoma, MPNST and others. Risk is set by FNCLCC grade, size and depth, and prognostic tools such as Sarculator translate these into individual estimates. The Rosenberg NCI trial of 1982 established that limb-sparing surgery with radiotherapy gives the same survival as amputation, and the NCIC SR2 trial of 2002 showed preoperative radiotherapy (50 Gy) and postoperative radiotherapy (66 Gy) give equal local control, with more acute wound complications after preoperative treatment but less late fibrosis, oedema and joint stiffness, which is why preoperative radiotherapy is now preferred for large deep tumours.
Perioperative chemotherapy has been contested for decades: the EORTC 62931 adjuvant trial was negative, but the Italian Sarcoma Group ISG-STS 1001 trial found that three cycles of neoadjuvant full-dose epirubicin-ifosfamide improved relapse-free and overall survival in high-risk limb and trunk sarcoma compared with histotype-tailored regimens, and it is offered to fit patients with large, deep, high-grade tumours. Isolated limb perfusion and regional hyperthermia with chemotherapy are used in selected centres to make unresectable tumours operable.
For advanced disease, EORTC 62012 randomised 455 patients to doxorubicin plus ifosfamide or doxorubicin alone: response and progression-free survival improved with the combination (median 7.4 versus 4.6 months) but overall survival did not significantly (14.3 versus 12.8 months), so doxorubicin alone remains standard unless tumour shrinkage is needed. The ANNOUNCE trial of olaratumab with doxorubicin was negative and withdrew the drug. Histology now drives later lines: gemcitabine-docetaxel and pazopanib across subtypes, trabectedin and eribulin for liposarcoma and leiomyosarcoma, and in leiomyosarcoma the French LMS-04 trial showed doxorubicin plus trabectedin followed by trabectedin maintenance roughly doubled progression-free survival compared with doxorubicin alone (median 12.2 versus 6.2 months), making it the first-line option for fit patients.
State of the art
- Preoperative radiotherapy with limb-sparing surgery is the standard for large deep limb sarcomas, trading early wound problems for better long-term function.
- ISG-STS 1001 revived neoadjuvant chemotherapy for high-risk disease after the negative EORTC 62931 adjuvant trial.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- LMS-04 made doxorubicin plus trabectedin the first histology-specific first-line regimen with a randomised progression-free survival gain.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowBowel perforation
Sudden severe abdominal pain, a hard or very tender abdomen, or abdominal pain with vomiting and fever. Boxed warning for gastrointestinal perforation on bevacizumab.
- Emergency services nowFainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
- Check before combiningFood and drink: Doxorubicin
Cumulative dose: risk rises steeply above 400-550 mg/m² (see the anthracycline calculator).
- Check before combiningFood and drink: Pazopanib
Take on an empty stomach (1 hour before or 2 hours after food).
- Check before combiningFood and drink: Trabectedin
Alcohol: avoid (hepatotoxicity). Dexamethasone 20 mg before each dose protects the liver.
See all on the product pages:DocetaxelDoxorubicinEribulinGemcitabineIfosfamidePazopanibTrabectedin·Printable cards in the navigator
Anatomy and lymph node drainage
- Metaphysis, near the growth plate (osteosarcoma)
- Shaft (Ewing sarcoma)
- Deep soft tissue compartment
- Skeletal muscle (rhabdomyosarcoma)
- Neurovascular bundle (limb salvage decision)
Bone sarcomas favour the fast-growing ends of long bones (osteosarcoma) or the shaft (Ewing), soft tissue sarcomas the deep muscle compartments; spread is through the blood to the lungs, rarely via lymph nodes.
- Metaphysis, near the growth plate (osteosarcoma)Localised high-grade, deep, over 5 cm soft tissue sarcoma of the limb (preoperative radiotherapy, neoadjuvant chemotherapy)
- Shaft (Ewing sarcoma)Localised low-grade soft tissue sarcoma of the limb (surgery, selective radiotherapy) · Localised high-grade, deep, over 5 cm soft tissue sarcoma of the limb (preoperative radiotherapy, neoadjuvant chemotherapy) · Oligometastatic lung disease (metastasectomy, stereotactic radiotherapy) · Advanced or metastatic soft tissue sarcoma (doxorubicin-based chemotherapy)
- Deep soft tissue compartmentLocalised low-grade soft tissue sarcoma of the limb (surgery, selective radiotherapy) · Localised high-grade, deep, over 5 cm soft tissue sarcoma of the limb (preoperative radiotherapy, neoadjuvant chemotherapy) · Locally advanced unresectable limb sarcoma (isolated limb perfusion, hyperthermia) · Advanced or metastatic soft tissue sarcoma (doxorubicin-based chemotherapy) · Advanced leiomyosarcoma (doxorubicin plus trabectedin, LMS-04)
- Skeletal muscle (rhabdomyosarcoma)
- Neurovascular bundle (limb salvage decision)
Lymph node spread is rare (except epithelioid, synovial, clear cell and rhabdomyosarcoma); sarcomas go through the blood to the lungs.
Same organ: Leiomyosarcoma, Liposarcoma, Synovial sarcoma, Sarcomas (soft tissue, bone, GIST), Osteosarcoma, Ewing sarcoma, Rhabdomyosarcoma, Chordoma, Desmoid tumour, Tenosynovial giant cell tumour (TGCT), Epithelioid sarcoma, Vascular tumours (angiosarcoma, epithelioid haemangioendothelioma, kaposiform haemangioendothelioma), Chondrosarcoma, Angiosarcoma, Undifferentiated pleomorphic sarcoma (UPS), Myxofibrosarcoma, Alveolar soft part sarcoma, Perivascular epithelioid cell tumour (PEComa), Epithelioid haemangioendothelioma, Malignant peripheral nerve sheath tumour (MPNST), Retroperitoneal sarcoma
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- About 60 percent of soft tissue sarcomas arise in the limbs, most often the thigh, across dozens of histologies; deep, high-grade tumours over five centimetres metastasise to the lungs in roughly a third to a half of patients, and advanced disease has a median survival of one to two years with chemotherapy.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Limb-sparing wide resection with preoperative (50 Gy) or postoperative (66 Gy) radiotherapy for high-grade or deep tumours over 5 cm; surgery alone for small superficial low-grade tumours.
Neoadjuvant anthracycline-ifosfamide (ISG-STS 1001) in fit patients; regional hyperthermia with chemotherapy or isolated limb perfusion for borderline resectable tumours.
Doxorubicin alone, or doxorubicin plus ifosfamide when shrinkage is needed (EORTC 62012); doxorubicin plus trabectedin for leiomyosarcoma (LMS-04); olaratumab withdrawn after ANNOUNCE.
Gemcitabine-docetaxel, pazopanib, trabectedin, eribulin (liposarcoma); pulmonary metastasectomy or stereotactic radiotherapy for limited lung disease; histology-directed agents and trials.
Subtypes & biomarkers
top- Localised low-grade soft tissue sarcoma of the limb (surgery, selective radiotherapy)
- Localised high-grade, deep, over 5 cm soft tissue sarcoma of the limb (preoperative radiotherapy, neoadjuvant chemotherapy)
- Locally advanced unresectable limb sarcoma (isolated limb perfusion, hyperthermia)
- Oligometastatic lung disease (metastasectomy, stereotactic radiotherapy)
- Advanced or metastatic soft tissue sarcoma (doxorubicin-based chemotherapy)
- Advanced leiomyosarcoma (doxorubicin plus trabectedin, LMS-04)
- FNCLCC grade, size over 5 cm and depth (Sarculator risk)
- Histological subtype by expert pathology and molecular testing
- Margin status after resection
- Lung CT staging and surveillance
How often this target appears
- 1982Rosenberg NCI trial: limb-sparing surgery plus radiotherapy equals amputation
- 2002NCIC SR2: preoperative and postoperative radiotherapy give equal control, with different toxicities
- 2012EORTC 62931: adjuvant doxorubicin-ifosfamide does not improve survival
- 2014EORTC 62012: doxorubicin plus ifosfamide improves response but not overall survival
- 2017ISG-STS 1001: neoadjuvant epirubicin-ifosfamide improves survival in high-risk limb sarcoma
- 2019ANNOUNCE: olaratumab fails and is withdrawn
- 2022LMS-04: doxorubicin plus trabectedin doubles progression-free survival in leiomyosarcoma
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 12 changes by month →- 2026-09-17This recordSoft tissue sarcoma of the extremity (localised and advanced)Facts on this page last checked
When this page itself was last checked or edited.
- 2022Trial resultLMS-04LMS-04 reported
Median PFS 12.
- 2022MilestoneLMS-04LMS-04: doxorubicin plus trabectedin doubles progression-free survival in leiomyosarcoma
A milestone in how this cancer is treated.
- 2019Trial resultANNOUNCEANNOUNCE reported
OS HR 1.
- 2019MilestoneANNOUNCEANNOUNCE: olaratumab fails and is withdrawn
A milestone in how this cancer is treated.
- 2017Trial resultISG-STS 1001ISG-STS 1001 reported
Standard arm DFS HR ~0.
What is in development for Soft tissue sarcoma of the extremity (localised and advanced), drawn from the whole corpus: 4 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Trials reported · 4
- LMS-04 · phase 3 · 2022 · positive
- ISG-STS 1001 · phase 3 · 2017 · positive
- ANNOUNCE · phase 3 · 2019 · negative
- EORTC 62012 · phase 3 · 2014 · completed
Open problems and what is being done
A third to a half of high-risk limb sarcomas still metastasise to the lungs.
and how the field plans to fix it →What is being done about thisAdvanced and metastatic diseaseAvailable now- DocetaxelApproved
- IMRT / IGRT (modern external beam)Standard of care
- SBRT / SABR (stereotactic radiotherapy)Standard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Atlas of advanced disease · Invasion and metastasis.
Chemotherapy prolongs control but rarely survival in advanced disease.
and how the field plans to fix it →What is being done about thisAdvanced and metastatic diseaseAvailable now- DocetaxelApproved
- IMRT / IGRT (modern external beam)Standard of care
- SBRT / SABR (stereotactic radiotherapy)Standard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Atlas of advanced disease · Invasion and metastasis.
Trials pool dozens of histologies that behave differently.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Stanford · university | United States | 0 | 3,000 | 50,162 | #30 | ||
Dallas, TX · cancer center | United States | 0 | 1,744 | 19,757 | - | ||
Utrecht · cancer center | Netherlands | none recorded | 0 | 1,422 | 20,323 | - | |
Tianjin · cancer center | China | none recorded | 0 | 1,219 | 11,455 | - | |
Hangzhou · cancer center | China | none recorded | 0 | 1,219 | 17,635 | - | |
Rozzano (Milan) · hospital | Italy | none recorded | 0 | 1,031 | 10,720 | - | |
Changsha · cancer center | China | none recorded | 0 | 930 | 14,477 | - | |
Jinan · cancer center | China | none recorded | 0 | 920 | 7,804 | - | |
Dresden · cancer center | Germany | none recorded | 0 | 728 | 7,984 | - | |
| United Kingdom | none recorded | 0 | 693 | 7,168 | - | ||
Chennai · cancer center | India | none recorded | 0 | 691 | 13,919 | - | |
Aarhus · hospital | Denmark | none recorded | 0 | 624 | 4,497 | - | |
Freiburg im Breisgau · cancer center | Germany | none recorded | 0 | 549 | 5,261 | - | |
Lausanne · hospital | Switzerland | none recorded | 0 | 509 | 9,176 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Soft tissue sarcoma of the extremity but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Soft tissue sarcoma of the extremity
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example FNCLCC grade, size over 5 cm and depth, Histological subtype by expert pathology and molecular testing, Margin status after resection, Lung CT staging and surveillance), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Localised low-grade soft tissue sarcoma of the limb, Localised high-grade, deep, over 5 cm soft tissue sarcoma of the limb, Locally advanced unresectable limb sarcoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Localised, resectable
- For my situation (localised, resectable), which of the standard options do you recommend and why?Why: Guideline options include: Limb-sparing wide resection with preoperative (50 Gy) or postoperative (66 Gy) radiotherapy for high-grade or deep tumours over 5 cm; surgery alone for small superficial low-grade tumours.
High-risk localised (large, deep, high grade)
- For my situation (high-risk localised (large, deep, high grade)), which of the standard options do you recommend and why?Why: Guideline options include: Neoadjuvant anthracycline-ifosfamide (ISG-STS 1001) in fit patients; regional hyperthermia with chemotherapy or isolated limb perfusion for borderline resectable tumours.
- Am I a candidate for Doxorubicin, Ifosfamide, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ISG-STS 1001 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Advanced, first line
- For my situation (advanced, first line), which of the standard options do you recommend and why?Why: Guideline options include: Doxorubicin alone, or doxorubicin plus ifosfamide when shrinkage is needed (EORTC 62012); doxorubicin plus trabectedin for leiomyosarcoma (LMS-04); olaratumab withdrawn after ANNOUNCE.
- Am I a candidate for Doxorubicin, Ifosfamide, Trabectedin, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of EORTC 62012 and LMS-04 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Later lines and oligometastatic
- For my situation (later lines and oligometastatic), which of the standard options do you recommend and why?Why: Guideline options include: Gemcitabine-docetaxel, pazopanib, trabectedin, eribulin (liposarcoma); pulmonary metastasectomy or stereotactic radiotherapy for limited lung disease; histology-directed agents and trials.
- Am I a candidate for Gemcitabine, Docetaxel, Pazopanib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of LMS-04, ISG-STS 1001, Trabectedin, Pembrolizumab?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “A third to a half of high-risk limb sarcomas still metastasise to the lungs”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Chemotherapy prolongs control but rarely survival in advanced disease”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Soft tissue sarcoma of the extremity, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
12targets
3drugs
8companies
6terms
2trials
4Latest papers
topQuery for this cancer: (TITLE:"Soft tissue sarcoma of the extremity" OR ABSTRACT:"Soft tissue sarcoma of the extremity" OR TITLE:"localised and advanced" OR ABSTRACT:"localised and advanced" OR TITLE:"Limb sarcoma" OR ABSTRACT:"Limb sarcoma" OR TITLE:"Extremity STS" OR ABSTRACT:"Extremity STS" OR TITLE:"Localised soft tissue sarcoma" OR ABSTRACT:"Localised soft tissue sarcoma" OR TITLE:"Advanced soft tissue sarcoma" OR ABSTRACT:"Advanced soft tissue sarcoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Soft tissue sarcoma of the extremity (localised and advanced), not a curated reading list.
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