# Soft tissue sarcoma of the extremity (localised and advanced)

Source: https://onco.cc/cancers/extremity-soft-tissue-sarcoma/  
OnCo record `extremity-soft-tissue-sarcoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Limb sarcoma; Extremity STS; Localised soft tissue sarcoma; Advanced soft tissue sarcoma
- Tags: subtype-page
- Group: sarcoma
- Burden: 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.
- Subtypes: 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)
- Biomarkers: 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

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/extremity-soft-tissue-sarcoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/extremity-soft-tissue-sarcoma/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/extremity-soft-tissue-sarcoma/#what-it-is [6 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/extremity-soft-tissue-sarcoma/#finding-it [4 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/extremity-soft-tissue-sarcoma/#treating-it [4 settings, 4 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/extremity-soft-tissue-sarcoma/#evidence [5 trials, 5 key papers, 7 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/extremity-soft-tissue-sarcoma/#science [3 targets]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/extremity-soft-tissue-sarcoma/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/extremity-soft-tissue-sarcoma/#living-with-it [18 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/extremity-soft-tissue-sarcoma/coming/ [8 medicines, 5 trials, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/extremity-soft-tissue-sarcoma/data/ [44 connected records]

## Standard of care

- Localised, resectable: 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. ([Limb-salvage surgery and endoprosthetic reconstruction](https://onco.cc/technologies/limb-salvage-surgery/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [FNCLCC grade (soft-tissue sarcoma)](https://onco.cc/terms/fnclcc-grade/))
- High-risk localised (large, deep, high grade): Neoadjuvant anthracycline-ifosfamide (ISG-STS 1001) in fit patients; regional hyperthermia with chemotherapy or isolated limb perfusion for borderline resectable tumours. ([ISG-STS 1001](https://onco.cc/trials/isg-sts-1001/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Ifosfamide](https://onco.cc/drugs/ifosfamide/), [Hyperthermia](https://onco.cc/technologies/hyperthermia/), [Isolated limb perfusion and infusion](https://onco.cc/technologies/isolated-limb-perfusion/))
- Advanced, first line: Doxorubicin alone, or doxorubicin plus ifosfamide when shrinkage is needed (EORTC 62012); doxorubicin plus trabectedin for leiomyosarcoma (LMS-04); olaratumab withdrawn after ANNOUNCE. ([Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Ifosfamide](https://onco.cc/drugs/ifosfamide/), [EORTC 62012](https://onco.cc/trials/eortc-62012/), [Trabectedin](https://onco.cc/drugs/trabectedin/), [LMS-04](https://onco.cc/trials/lms-04/), [ANNOUNCE](https://onco.cc/trials/announce/))
- Later lines and oligometastatic: Gemcitabine-docetaxel, pazopanib, trabectedin, eribulin (liposarcoma); pulmonary metastasectomy or stereotactic radiotherapy for limited lung disease; histology-directed agents and trials. ([Gemcitabine](https://onco.cc/drugs/gemcitabine/), [Docetaxel](https://onco.cc/drugs/docetaxel/), [Pazopanib](https://onco.cc/drugs/pazopanib/), [Trabectedin](https://onco.cc/drugs/trabectedin/), [Eribulin](https://onco.cc/drugs/eribulin/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/), [Histotype-tailored therapy](https://onco.cc/terms/sarcoma-histotype-tailoring/))

## 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.
- LMS-04 made doxorubicin plus trabectedin the first histology-specific first-line regimen with a randomised progression-free survival gain.

## Open problems

- A third to a half of high-risk limb sarcomas still metastasise to the lungs.
- Chemotherapy prolongs control but rarely survival in advanced disease.
- Trials pool dozens of histologies that behave differently.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Soft-tissue_sarcoma
- Wikipedia: https://en.wikipedia.org/wiki/Soft-tissue_sarcoma

## Connected records

- cancers: [Alveolar soft part sarcoma](https://onco.cc/cancers/alveolar-soft-part-sarcoma/), [Chondrosarcoma](https://onco.cc/cancers/chondrosarcoma/), [Leiomyosarcoma](https://onco.cc/cancers/leiomyosarcoma/), [Liposarcoma](https://onco.cc/cancers/liposarcoma/), [Malignant peripheral nerve sheath tumour (MPNST)](https://onco.cc/cancers/malignant-peripheral-nerve-sheath-tumour/), [Myxofibrosarcoma](https://onco.cc/cancers/myxofibrosarcoma/), [Retroperitoneal sarcoma](https://onco.cc/cancers/retroperitoneal-sarcoma/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/), [Synovial sarcoma](https://onco.cc/cancers/synovial-sarcoma/), [Undifferentiated pleomorphic sarcoma (UPS)](https://onco.cc/cancers/undifferentiated-pleomorphic-sarcoma/)
- key papers: [EORTC 62012: doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced soft tissue sarcoma](https://onco.cc/key-papers/paper-eortc-62012-doxorubicin-ifosfamide-judson-lancet-oncol-2014/), [ISG-STS 1001: histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in high-risk soft tissue sarcoma](https://onco.cc/key-papers/paper-isg-sts-1001-gronchi-lancet-oncol-2017/), [LMS-04: doxorubicin plus trabectedin followed by trabectedin maintenance versus doxorubicin alone in metastatic leiomyosarcoma](https://onco.cc/key-papers/paper-lms-04-doxorubicin-trabectedin-lancet-oncol-2022/), [NCIC SR2: preoperative versus postoperative radiotherapy in soft tissue sarcoma of the limbs](https://onco.cc/key-papers/paper-ncic-sr2-preoperative-vs-postoperative-radiotherapy-osullivan-lancet-2002/), [Soft tissue and visceral sarcomas: ESMO-EURACAN-GENTURIS clinical practice guideline](https://onco.cc/key-papers/paper-esmo-sts-guideline-gronchi-ann-oncol-2021/)
- technologies: [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [Hyperthermia](https://onco.cc/technologies/hyperthermia/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Isolated limb perfusion and infusion](https://onco.cc/technologies/isolated-limb-perfusion/), [Limb-salvage surgery and endoprosthetic reconstruction](https://onco.cc/technologies/limb-salvage-surgery/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/)
- drugs: [Docetaxel](https://onco.cc/drugs/docetaxel/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Eribulin](https://onco.cc/drugs/eribulin/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/), [Ifosfamide](https://onco.cc/drugs/ifosfamide/), [Pazopanib](https://onco.cc/drugs/pazopanib/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Trabectedin](https://onco.cc/drugs/trabectedin/)
- trials: [A Clinical Study to Investigate the Efficacy of Intratumoral Tigilanol Tiglate in Soft Tissue Sarcoma](https://onco.cc/trials/nct05755113/), [ANNOUNCE](https://onco.cc/trials/announce/), [EORTC 62012](https://onco.cc/trials/eortc-62012/), [ISG-STS 1001](https://onco.cc/trials/isg-sts-1001/), [LMS-04](https://onco.cc/trials/lms-04/)
- terms: [FNCLCC grade (soft-tissue sarcoma)](https://onco.cc/terms/fnclcc-grade/), [Histotype-tailored therapy](https://onco.cc/terms/sarcoma-histotype-tailoring/)
- people: [Patricia Pautier](https://onco.cc/people/patricia-pautier/)
- companies: [French Sarcoma Group](https://onco.cc/companies/french-sarcoma-group/), [Italian Sarcoma Group](https://onco.cc/companies/italian-sarcoma-group/)

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JSON: https://onco.cc/api/v1/entities/extremity-soft-tissue-sarcoma.json