Uterine sarcoma
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 cures many early tumours; low-grade stromal sarcomas respond to hormone-blocking pills, while advanced leiomyosarcoma is treated with chemotherapy such as doxorubicin and trabectedin.
Overview
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.
Treatment 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.
The 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.
State of the art today
- 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.
Where it starts and where it drains
Most high-grade ovarian cancers begin at the tip of the fallopian tube; endometrial cancer lines the uterus, cervical cancer starts at the transformation zone; each drains to a different node group.
- Fallopian tube fimbria (origin of high-grade serous)
- Ovary (other histologies, germ cell)
- EndometriumLow-grade endometrial stromal sarcoma (JAZF1-SUZ12) · High-grade endometrial stromal sarcoma (YWHAE-NUTM2, BCOR)
- Myometrium (uterine sarcoma)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
- Placental site (gestational trophoblastic)
- Cervix, transformation zone
- Vulva
- obturator and external iliac
- internal iliac
- para-aortic (ovary, high uterus)
- inguinal (vulva)
Same organ: Ovarian cancer, Endometrial cancer, Cervical cancer, Vulvar cancer, Gestational trophoblastic neoplasia, Vaginal cancer
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.
- AI in radiologyEstablished
- cfDNA fragmentomicsEstablished
- Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Standard of care
- DNA methylation profilingEstablished
- HCC surveillance in cirrhosis (ultrasound + AFP)Standard of care
- High-risk pancreatic surveillance (CAPS / PRECEDE)Established
- A 28-day national pathway for people with a positive multi-cancer blood test
- A breath test to rule out cancer in people with vague symptoms
- A cancer blood test for older people arriving at A&E with unexplained symptoms
- A legislated, publicly reported 28-day standard from urgent referral to diagnosis
- A live national dashboard of stage at diagnosis as the scorecard for early detection
- A single 'cancer check at 60' appointment bundling all screening tests
Background: Alpha-fetoprotein (AFP), Barrett's oesophagus, CA 19-9, Early detection, Faecal immunochemical test (FIT). Also on OnCo: Symptoms and red flags · Early detection roadmap.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
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.
Doxorubicin alone or with trabectedin (LMS-04); gemcitabine-docetaxel; trabectedin, pazopanib or eribulin in later lines.
Aromatase inhibitor (letrozole) or progestin; avoid estrogen and tamoxifen; surgery for resectable recurrence.
Larotrectinib or entrectinib for NTRK fusions, crizotinib or alectinib for ALK, imatinib for COL1A1-PDGFB.
Subtypes & biomarkers
top- 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
- 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
Target prevalence in this cancer
- 2008EORTC 55874: adjuvant pelvic radiotherapy does not improve survival in uterine sarcoma
- 2012JAZF1-SUZ12 and YWHAE-NUTM2 fusions define low- and high-grade ESS
Lee and colleagues; earlier Koontz 2001 for JAZF1.
- 2014FDA warns against power morcellation
Unsuspected uterine sarcoma disseminated by morcellation during fibroid surgery.
- 2017GeDDiS: gemcitabine-docetaxel not superior to doxorubicin
Seddon and colleagues, Lancet Oncol; doxorubicin retained as first line.
- 2018GOG-0277 closed early
Adjuvant chemotherapy for stage I LMS did not improve outcomes; observation is standard.
- 2022LMS-04: doxorubicin plus trabectedin improves progression-free survival
Pautier and colleagues, Lancet Oncol.
Open problems, and what is being done about each
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.
and how the field plans to fix it →What is being done about thisRare cancers and small trialsAvailable now- LarotrectinibApproved
- AI trial matching & clinical decision supportEstablished
- Comprehensive genomic profilingStandard of care
- Dinutuximab (ch14.18) / dinutuximab betaApproved
- Eflornithine (DFMO)Approved
- Limb-salvage surgery and endoprosthetic reconstructionStandard of care
In trials- ACTIONRecruiting
- COG AALL1731Positive
- COG ANBL0032Positive
- DeFiPositive
- Euro Ewing 2012Positive
- Functional (ex vivo) drug testingEmerging
Ideas and roadmaps- A digital second-opinion network answering community oncologists within 72 hours
- A DRUP-style protocol for off-label generic targeted drugs in rare tumours
- A funded expert second opinion for every new high-stakes or rare cancer diagnosis
- A global first-in-human network for academic cancer trials with single ethics review
- A global open trials operating system any hospital can plug into
- A live 'seats available' feed for trial slots, like airline inventory
Background: Basket, umbrella, and platform trials, Centralisation and high-volume centres, FNCLCC grade (soft-tissue sarcoma), Histotype-tailored therapy, INRG staging and risk groups. Also on OnCo: Find a trial · Expert centres.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Expert centres
topCentres linked to this cancer in OnCo
- via Larotrectinib, Entrectinib, Crizotinib
- via Docetaxel, Endocrine therapy (SERMs, AIs, SERDs)
- via Endocrine therapy (SERMs, AIs, SERDs)
- via Endocrine therapy (SERMs, AIs, SERDs)
- via Endocrine therapy (SERMs, AIs, SERDs)
- Breast Cancer TrialsNewcastle, NSW, AUvia Endocrine therapy (SERMs, AIs, SERDs)
- Central Drugs Standard Control OrganizationNew Delhi, INvia Imatinib
- Children's Hospital of PhiladelphiaPhiladelphia, PA, USvia Crizotinib
- via Endocrine therapy (SERMs, AIs, SERDs)
- Dan L Duncan Comprehensive Cancer Center, Baylor College of MedicineHouston, TX, USNCI comprehensivevia Endocrine therapy (SERMs, AIs, SERDs)
- Edinburgh Cancer Centre / CRUK Scotland CentreEdinburgh, GBvia Endocrine therapy (SERMs, AIs, SERDs)
- ETOP IBCSG Partners FoundationBern, CHvia Endocrine therapy (SERMs, AIs, SERDs)
- GEICAM Spanish Breast Cancer GroupMadrid, ESvia Endocrine therapy (SERMs, AIs, SERDs)
- GIMEMARome, ITvia Imatinib
- Institut Jules BordetBrussels, BEvia Endocrine therapy (SERMs, AIs, SERDs)
- via Gemcitabine
- NSABP FoundationPittsburgh, PA, USvia Endocrine therapy (SERMs, AIs, SERDs)
- via Imatinib
- Seoul St. Mary's HospitalSeoul, KRvia Imatinib
Questions to ask
topQuestions to ask your oncologist about Uterine sarcoma
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 Histological subtype and mitotic count, Estrogen and progesterone receptor status, Fusion testing: JAZF1, YWHAE, BCOR, NTRK, ALK, Homologous recombination deficiency and BRCA alterations, Stage and whether the tumour was morcellated), 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 Uterine leiomyosarcoma, Low-grade endometrial stromal sarcoma, High-grade endometrial stromal sarcoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Localised, any subtype
- For my situation (localised, any subtype), which of the standard options do you recommend and why?Why: Guideline options include: 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.
Advanced or recurrent leiomyosarcoma
- For my situation (advanced or recurrent leiomyosarcoma), which of the standard options do you recommend and why?Why: Guideline options include: Doxorubicin alone or with trabectedin (LMS-04); gemcitabine-docetaxel; trabectedin, pazopanib or eribulin in later lines.
- Am I a candidate for Doxorubicin, Trabectedin, Gemcitabine or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Low-grade endometrial stromal sarcoma
- For my situation (low-grade endometrial stromal sarcoma), which of the standard options do you recommend and why?Why: Guideline options include: Aromatase inhibitor (letrozole) or progestin; avoid estrogen and tamoxifen; surgery for resectable recurrence.
- Am I a candidate for Letrozole (and other aromatase inhibitors), Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD), and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Fusion-driven sarcoma
- For my situation (fusion-driven sarcoma), which of the standard options do you recommend and why?Why: Guideline options include: Larotrectinib or entrectinib for NTRK fusions, crizotinib or alectinib for ALK, imatinib for COL1A1-PDGFB.
- Am I a candidate for Larotrectinib, Entrectinib, Crizotinib 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 Trabectedin, Larotrectinib, Pazopanib?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 “Preoperative distinction of leiomyosarcoma from fibroids: MRI and LDH criteria and imaging AI are under study”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Advanced LMS remains chemoresistant after two lines: PARP inhibitors for the HRD subset and antibody-drug conjugates are in trials”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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Direct links plus the targets, companies, and technologies of this cancer's products.
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topQuery for this cancer: (TITLE:"Uterine sarcoma" OR ABSTRACT:"Uterine sarcoma" OR TITLE:"Leiomyosarcoma of the uterus" OR ABSTRACT:"Leiomyosarcoma of the uterus" OR TITLE:"Endometrial stromal sarcoma" OR ABSTRACT:"Endometrial stromal sarcoma" OR TITLE:"Undifferentiated uterine sarcoma" OR ABSTRACT:"Undifferentiated uterine sarcoma" OR TITLE:"Uterine LMS" OR ABSTRACT:"Uterine LMS" OR TITLE:"ESS" OR ABSTRACT:"ESS") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Uterine sarcoma, not a curated reading list.
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