{"entity":{"id":"extremity-soft-tissue-sarcoma","kind":"cancer","name":"Soft tissue sarcoma of the extremity (localised and advanced)","aka":["Limb sarcoma","Extremity STS","Localised soft tissue sarcoma","Advanced soft tissue sarcoma"],"tldr":"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.\n\nPerioperative 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.\n\nFor 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.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Soft-tissue_sarcoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Soft-tissue_sarcoma"}],"tags":["subtype-page"],"related":["sarcoma","leiomyosarcoma","uterine-sarcoma","liposarcoma","synovial-sarcoma","undifferentiated-pleomorphic-sarcoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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"],"standardOfCare":[{"setting":"Localised, resectable","approach":"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.","refs":["limb-salvage-surgery","imrt-igrt","brachytherapy","fnclcc-grade"]},{"setting":"High-risk localised (large, deep, high grade)","approach":"Neoadjuvant anthracycline-ifosfamide (ISG-STS 1001) in fit patients; regional hyperthermia with chemotherapy or isolated limb perfusion for borderline resectable tumours.","refs":["isg-sts-1001","doxorubicin","ifosfamide","hyperthermia","isolated-limb-perfusion"]},{"setting":"Advanced, first line","approach":"Doxorubicin alone, or doxorubicin plus ifosfamide when shrinkage is needed (EORTC 62012); doxorubicin plus trabectedin for leiomyosarcoma (LMS-04); olaratumab withdrawn after ANNOUNCE.","refs":["doxorubicin","ifosfamide","eortc-62012","trabectedin","lms-04","announce"]},{"setting":"Later lines and oligometastatic","approach":"Gemcitabine-docetaxel, pazopanib, trabectedin, eribulin (liposarcoma); pulmonary metastasectomy or stereotactic radiotherapy for limited lung disease; histology-directed agents and trials.","refs":["gemcitabine","docetaxel","pazopanib","trabectedin","eribulin","sbrt","sarcoma-histotype-tailoring"]}],"stateOfArt":["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."],"history":[{"year":1982,"title":"Rosenberg NCI trial: limb-sparing surgery plus radiotherapy equals amputation","refs":["limb-salvage-surgery"]},{"year":2002,"title":"NCIC SR2: preoperative and postoperative radiotherapy give equal control, with different toxicities","refs":["imrt-igrt"]},{"year":2012,"title":"EORTC 62931: adjuvant doxorubicin-ifosfamide does not improve survival","refs":["doxorubicin","ifosfamide"]},{"year":2014,"title":"EORTC 62012: doxorubicin plus ifosfamide improves response but not overall survival","refs":["eortc-62012"]},{"year":2017,"title":"ISG-STS 1001: neoadjuvant epirubicin-ifosfamide improves survival in high-risk limb sarcoma","refs":["isg-sts-1001"]},{"year":2019,"title":"ANNOUNCE: olaratumab fails and is withdrawn","refs":["announce"]},{"year":2022,"title":"LMS-04: doxorubicin plus trabectedin doubles progression-free survival in leiomyosarcoma","refs":["lms-04"]}],"pipeline":["lms-04","isg-sts-1001","trabectedin","pembrolizumab"],"openProblems":["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."],"parent":"sarcoma"},"route":"/cancers/extremity-soft-tissue-sarcoma/","neighbours":{"cancer":[{"id":"alveolar-soft-part-sarcoma","kind":"cancer","name":"Alveolar soft part sarcoma","route":"/cancers/alveolar-soft-part-sarcoma/"},{"id":"leiomyosarcoma","kind":"cancer","name":"Leiomyosarcoma","route":"/cancers/leiomyosarcoma/"},{"id":"liposarcoma","kind":"cancer","name":"Liposarcoma","route":"/cancers/liposarcoma/"},{"id":"malignant-peripheral-nerve-sheath-tumour","kind":"cancer","name":"Malignant peripheral nerve sheath tumour (MPNST)","route":"/cancers/malignant-peripheral-nerve-sheath-tumour/"},{"id":"myxofibrosarcoma","kind":"cancer","name":"Myxofibrosarcoma","route":"/cancers/myxofibrosarcoma/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"synovial-sarcoma","kind":"cancer","name":"Synovial sarcoma","route":"/cancers/synovial-sarcoma/"},{"id":"undifferentiated-pleomorphic-sarcoma","kind":"cancer","name":"Undifferentiated pleomorphic sarcoma (UPS)","route":"/cancers/undifferentiated-pleomorphic-sarcoma/"},{"id":"uterine-sarcoma","kind":"cancer","name":"Uterine sarcoma","route":"/cancers/uterine-sarcoma/"}],"technology":[{"id":"brachytherapy","kind":"technology","name":"Brachytherapy","route":"/technologies/brachytherapy/"},{"id":"hyperthermia","kind":"technology","name":"Hyperthermia","route":"/technologies/hyperthermia/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"isolated-limb-perfusion","kind":"technology","name":"Isolated limb perfusion and infusion","route":"/technologies/isolated-limb-perfusion/"},{"id":"limb-salvage-surgery","kind":"technology","name":"Limb-salvage surgery and endoprosthetic reconstruction","route":"/technologies/limb-salvage-surgery/"},{"id":"sbrt","kind":"technology","name":"SBRT / SABR (stereotactic radiotherapy)","route":"/technologies/sbrt/"}],"drug":[{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"eribulin","kind":"drug","name":"Eribulin","route":"/drugs/eribulin/"},{"id":"gemcitabine","kind":"drug","name":"Gemcitabine","route":"/drugs/gemcitabine/"},{"id":"ifosfamide","kind":"drug","name":"Ifosfamide","route":"/drugs/ifosfamide/"},{"id":"pazopanib","kind":"drug","name":"Pazopanib","route":"/drugs/pazopanib/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trabectedin","kind":"drug","name":"Trabectedin","route":"/drugs/trabectedin/"}],"trial":[{"id":"announce","kind":"trial","name":"ANNOUNCE","route":"/trials/announce/"},{"id":"eortc-62012","kind":"trial","name":"EORTC 62012","route":"/trials/eortc-62012/"},{"id":"isg-sts-1001","kind":"trial","name":"ISG-STS 1001","route":"/trials/isg-sts-1001/"},{"id":"lms-04","kind":"trial","name":"LMS-04","route":"/trials/lms-04/"}],"term":[{"id":"fnclcc-grade","kind":"term","name":"FNCLCC grade (soft-tissue sarcoma)","route":"/terms/fnclcc-grade/"},{"id":"sarcoma-histotype-tailoring","kind":"term","name":"Histotype-tailored therapy","route":"/terms/sarcoma-histotype-tailoring/"}]}}