{"entity":{"id":"uterine-sarcoma","kind":"cancer","name":"Uterine sarcoma","aka":["Leiomyosarcoma of the uterus","Endometrial stromal sarcoma","Undifferentiated uterine sarcoma","Uterine LMS","ESS"],"tldr":"Uterine sarcomas are rare cancers of the muscle and supporting tissue of the womb, distinct from the far commoner endometrial cancer. Removing the uterus intact is the main treatment and is followed by observation for stage I disease; low-grade stromal sarcomas respond to hormone-blocking pills, while advanced leiomyosarcoma is treated with doxorubicin and trabectedin.","summary":"Uterine sarcomas comprise leiomyosarcoma (LMS, the majority), low-grade and high-grade endometrial stromal sarcoma (ESS), undifferentiated uterine sarcoma, adenosarcoma, and a growing set of molecularly defined entities: JAZF1-SUZ12 fusions in low-grade ESS, YWHAE-NUTM2 and BCOR alterations in high-grade ESS, and rare NTRK-, ALK- or COL1A1-PDGFB-rearranged uterine sarcomas that have matched targeted drugs. LMS is often diagnosed after hysterectomy or myomectomy for presumed fibroids; power morcellation of an unsuspected LMS disseminates tumour and worsens outcome, which led the FDA to restrict the practice in 2014.\n\nTreatment of localised disease is total hysterectomy with intact removal; oophorectomy is standard for ESS (hormone-sensitive) but optional in premenopausal LMS. Adjuvant chemotherapy did not improve outcomes in the randomised GOG-0277 trial (gemcitabine-docetaxel followed by doxorubicin versus observation, closed early) and adjuvant radiotherapy did not improve survival in EORTC 55874, so observation is standard after complete resection of stage I LMS. For advanced LMS, doxorubicin-based therapy is first line (GeDDiS showed gemcitabine-docetaxel was not superior to doxorubicin; LMS-04 showed doxorubicin plus trabectedin improved progression-free survival over doxorubicin alone), followed by trabectedin, gemcitabine-docetaxel or pazopanib. Low-grade ESS is treated with aromatase inhibitors or progestins, not chemotherapy, and estrogen must be avoided.\n\nThe frontier is molecular: fusion-directed therapy for NTRK and ALK cases, and trials of PARP inhibitors and immunotherapy in the subset of LMS with homologous recombination deficiency or high mutation burden.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Uterine_sarcoma","links":[{"label":"NCI PDQ: uterine sarcoma","url":"https://www.cancer.gov/types/uterine/patient/uterine-sarcoma-treatment-pdq"},{"label":"NCCN Uterine Neoplasms","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1473"},{"label":"LMS-04 (Lancet Oncol 2022)","url":"https://doi.org/10.1016/S1470-2045(22)00380-1"},{"label":"GeDDiS (Lancet Oncol 2017)","url":"https://doi.org/10.1016/S1470-2045(17)30622-8"}],"tags":["nci-coverage","rare","gynaecologic","sarcoma"],"related":["leiomyosarcoma","retroperitoneal-sarcoma","liposarcoma","pecoma"],"cancers":[],"sections":[],"technologies":["cytotoxic-chemotherapy","endocrine-therapy","kinase-inhibitors","mri"],"targets":["estrogen-receptor","ntrk","alk","parp"],"drugs":["doxorubicin","trabectedin","gemcitabine","docetaxel","pazopanib","eribulin","letrozole","megestrol-progestins","larotrectinib","entrectinib","crizotinib"],"companies":[],"institutions":[],"pathways":["er-signaling","homologous-recombination-repair"],"terms":["hysterectomy","rare-cancers"],"trials":["nct06088290"],"people":[],"bottlenecks":["b-rare-cancers"],"keyPapers":["paper-seddon-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"group":"gynaecologic","burden":"About 3 to 4 percent of uterine cancers; leiomyosarcoma is the most common type, typically diagnosed in women in their fifties, often unexpectedly after surgery for presumed fibroids.","subtypes":["Uterine leiomyosarcoma","Low-grade endometrial stromal sarcoma (JAZF1-SUZ12)","High-grade endometrial stromal sarcoma (YWHAE-NUTM2, BCOR)","Undifferentiated uterine sarcoma","Adenosarcoma","NTRK-, ALK- or PDGFB-rearranged uterine sarcoma"],"biomarkers":["Histological subtype and mitotic count","Estrogen and progesterone receptor status (ESS, some LMS)","Fusion testing: JAZF1, YWHAE, BCOR, NTRK, ALK","Homologous recombination deficiency and BRCA alterations (subset of LMS)","Stage and whether the tumour was morcellated"],"standardOfCare":[{"setting":"Localised, any subtype","approach":"Total hysterectomy with intact removal (no morcellation); bilateral salpingo-oophorectomy for ESS; observation after complete resection of stage I LMS because adjuvant chemotherapy (GOG-0277) and radiotherapy (EORTC 55874) did not improve survival.","refs":["hysterectomy"],"guideline":{"nccn":"Category 2A","version":"NCCN Uterine Neoplasms; ESGO-EURACAN-GCIG guideline","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1473"}},{"setting":"Advanced or recurrent leiomyosarcoma","approach":"Doxorubicin alone or with trabectedin (LMS-04); gemcitabine-docetaxel; trabectedin, pazopanib or eribulin in later lines.","refs":["doxorubicin","trabectedin","gemcitabine","docetaxel","pazopanib","eribulin"],"guideline":{"nccn":"Category 2A","version":"NCCN Uterine Neoplasms"}},{"setting":"Low-grade endometrial stromal sarcoma","approach":"Aromatase inhibitor (letrozole) or progestin; avoid estrogen and tamoxifen; surgery for resectable recurrence.","refs":["letrozole","megestrol-progestins","endocrine-therapy"]},{"setting":"Fusion-driven sarcoma","approach":"Larotrectinib or entrectinib for NTRK fusions, crizotinib or alectinib for ALK, imatinib for COL1A1-PDGFB.","refs":["larotrectinib","entrectinib","crizotinib","imatinib"]}],"stateOfArt":["Molecular reclassification (JAZF1, YWHAE, BCOR, NTRK, ALK) has split what was one histology into entities with different behaviour and, for some, matched drugs.","Two randomised trials showed that adjuvant chemotherapy and radiotherapy do not help after complete resection, sparing patients toxicity: observation is the evidence-based standard.","LMS-04 established doxorubicin plus trabectedin as a first-line option for advanced leiomyosarcoma.","Avoiding morcellation of unsuspected sarcomas changed gynaecological surgery practice worldwide after 2014."],"history":[{"year":2008,"title":"EORTC 55874: adjuvant pelvic radiotherapy does not improve survival in uterine sarcoma","refs":[]},{"year":2012,"title":"JAZF1-SUZ12 and YWHAE-NUTM2 fusions define low- and high-grade ESS","note":"Lee and colleagues; earlier Koontz 2001 for JAZF1.","refs":[]},{"year":2014,"title":"FDA warns against power morcellation","note":"Unsuspected uterine sarcoma disseminated by morcellation during fibroid surgery.","refs":[]},{"year":2017,"title":"GeDDiS: gemcitabine-docetaxel not superior to doxorubicin","note":"Seddon and colleagues, Lancet Oncol; doxorubicin retained as first line.","refs":["doxorubicin"]},{"year":2018,"title":"GOG-0277 closed early","note":"Adjuvant chemotherapy for stage I LMS did not improve outcomes; observation is standard.","refs":["gemcitabine","docetaxel"]},{"year":2022,"title":"LMS-04: doxorubicin plus trabectedin improves progression-free survival","note":"Pautier and colleagues, Lancet Oncol.","refs":["doxorubicin","trabectedin"]}],"pipeline":["trabectedin","larotrectinib","pazopanib"],"openProblems":["Preoperative distinction of leiomyosarcoma from fibroids: MRI and LDH criteria and imaging AI are under study.","Advanced LMS remains chemoresistant after two lines: PARP inhibitors for the HRD subset and antibody-drug conjugates are in trials.","High-grade ESS and undifferentiated sarcoma have no proven standard beyond anthracycline.","Rarity limits randomised evidence: international sarcoma consortia are pooling trials."],"parent":"sarcoma"},"route":"/cancers/uterine-sarcoma/","neighbours":{"cancer":[{"id":"leiomyosarcoma","kind":"cancer","name":"Leiomyosarcoma","route":"/cancers/leiomyosarcoma/"},{"id":"liposarcoma","kind":"cancer","name":"Liposarcoma","route":"/cancers/liposarcoma/"},{"id":"pecoma","kind":"cancer","name":"Perivascular epithelioid cell tumour (PEComa)","route":"/cancers/pecoma/"},{"id":"retroperitoneal-sarcoma","kind":"cancer","name":"Retroperitoneal sarcoma","route":"/cancers/retroperitoneal-sarcoma/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"endocrine-therapy","kind":"technology","name":"Endocrine therapy (SERMs, AIs, SERDs)","route":"/technologies/endocrine-therapy/"},{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/"},{"id":"estrogen-receptor","kind":"target","name":"Estrogen receptor (ERα)","route":"/targets/estrogen-receptor/"},{"id":"ntrk","kind":"target","name":"NTRK","route":"/targets/ntrk/"},{"id":"parp","kind":"target","name":"PARP","route":"/targets/parp/"}],"drug":[{"id":"crizotinib","kind":"drug","name":"Crizotinib","route":"/drugs/crizotinib/"},{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"entrectinib","kind":"drug","name":"Entrectinib","route":"/drugs/entrectinib/"},{"id":"eribulin","kind":"drug","name":"Eribulin","route":"/drugs/eribulin/"},{"id":"gemcitabine","kind":"drug","name":"Gemcitabine","route":"/drugs/gemcitabine/"},{"id":"imatinib","kind":"drug","name":"Imatinib","route":"/drugs/imatinib/"},{"id":"larotrectinib","kind":"drug","name":"Larotrectinib","route":"/drugs/larotrectinib/"},{"id":"letrozole","kind":"drug","name":"Letrozole (and other aromatase inhibitors)","route":"/drugs/letrozole/"},{"id":"pazopanib","kind":"drug","name":"Pazopanib","route":"/drugs/pazopanib/"},{"id":"megestrol-progestins","kind":"drug","name":"Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD)","route":"/drugs/megestrol-progestins/"},{"id":"trabectedin","kind":"drug","name":"Trabectedin","route":"/drugs/trabectedin/"}],"pathway":[{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"},{"id":"er-signaling","kind":"pathway","name":"Oestrogen receptor signalling","route":"/pathways/er-signaling/"}],"term":[{"id":"hysterectomy","kind":"term","name":"Hysterectomy","route":"/terms/hysterectomy/"},{"id":"rare-cancers","kind":"term","name":"Rare cancers","route":"/terms/rare-cancers/"}],"trial":[{"id":"nct04554914","kind":"trial","name":"A Study to Evaluate Tabelecleucel in Participants With Epstein Barr Virus (EBV) Associated Diseases","route":"/trials/nct04554914/"},{"id":"lms-04","kind":"trial","name":"LMS-04","route":"/trials/lms-04/"},{"id":"nct06277154","kind":"trial","name":"MASCT-I Combined With Doxorubicin and Ifosfamide for First-line Treatment of Advanced Soft Tissue Sarcoma","route":"/trials/nct06277154/"},{"id":"nct06975293","kind":"trial","name":"STC-15 as a Part of Combination Therapy With Toripalimab in Selected Advanced Cancers and as Monotherapy in Participants With Selected Sarcomas","route":"/trials/nct06975293/"},{"id":"nct06088290","kind":"trial","name":"Study of Lurbinectedin in Combination With Doxorubicin Versus Doxorubicin Alone as First-line Treatment in Participants With Metastatic Leiomyosarcoma (SaLuDo)","route":"/trials/nct06088290/"},{"id":"nct00390234","kind":"trial","name":"Ziv-aflibercept in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gynecologic Soft Tissue Sarcoma","route":"/trials/nct00390234/"}],"bottleneck":[{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"}],"paper":[{"id":"paper-seddon-lancet-oncol","kind":"paper","name":"Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial","route":"/key-papers/paper-seddon-lancet-oncol/"}],"journal":[{"id":"international-journal-of-gynecological-cancer","kind":"journal","name":"International journal of gynecological cancer","route":"/journals/international-journal-of-gynecological-cancer/"},{"id":"journal-of-gynecologic-oncology","kind":"journal","name":"Journal of gynecologic oncology","route":"/journals/journal-of-gynecologic-oncology/"}],"company":[{"id":"french-sarcoma-group","kind":"company","name":"French Sarcoma Group","route":"/companies/french-sarcoma-group/"},{"id":"ptc-therapeutics","kind":"company","name":"PTC Therapeutics","route":"/companies/ptc-therapeutics/"}]}}