Epithelioid sarcoma
Epithelioid sarcoma is a rare soft tissue cancer that has lost a gene brake called SMARCB1, leaving it dependent on the enzyme EZH2. Surgery cures localised tumours, and the EZH2 inhibitor tazemetostat, the first epigenetic drug approved for a solid tumour, gives durable disease control in some advanced cases.
Overview
Epithelioid sarcoma is defined by loss of SMARCB1 (INI1), a core subunit of the SWI/SNF chromatin-remodelling complex, in over 90 percent of cases. SWI/SNF loss makes cells dependent on the antagonistic polycomb repressive complex 2 and its catalytic subunit EZH2, a synthetic-lethal relationship demonstrated in preclinical models and confirmed in patients. The distal (classic) type presents as slow-growing nodules on the hands and forearms of young adults and is often misdiagnosed as a benign lesion; the proximal type, in the pelvis, perineum and trunk, is larger and more aggressive, with rhabdoid features. Both spread to lymph nodes, which is unusual for sarcomas, and to lung.
Localised disease is treated with wide resection and radiotherapy according to soft tissue sarcoma principles; sentinel node evaluation is considered because of nodal spread. Conventional chemotherapy (anthracycline, ifosfamide, gemcitabine-docetaxel) has modest activity. Tazemetostat received FDA accelerated approval in January 2020 for metastatic or locally advanced epithelioid sarcoma not eligible for complete resection, on the basis of the single-arm EZH-202 cohort (objective responses in a minority, but durable, with a benign safety profile). The confirmatory randomised trial EZH-301 adds tazemetostat to doxorubicin in the first line; its result determines whether the accelerated approval is converted or withdrawn, and at the time of writing the read-out is pending.
Beyond EZH2, checkpoint inhibitors have produced occasional responses (SWI/SNF-deficient tumours are immunogenic in some settings), and combinations of tazemetostat with doxorubicin or immunotherapy are the main directions.
State of the art today
- Tazemetostat is the first EZH2 inhibitor and the first epigenetic drug approved for a solid tumour, and epithelioid sarcoma is the disease that made the SWI/SNF-EZH2 synthetic lethality a clinical reality.
- The approval rests on a single-arm cohort; the randomised EZH-301 confirmatory trial with doxorubicin is the test of whether the benefit holds in first line.
- Nodal spread and frequent misdiagnosis of distal lesions mean that expert pathology review and sarcoma-centre referral change outcomes.
- SMARCB1 loss links this tumour to ATRT, poorly differentiated chordoma and renal medullary carcinoma, allowing shared trials across rare SWI/SNF-deficient cancers.
Where it starts and where it drains
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)
- Shaft (Ewing sarcoma)
- Deep soft tissue compartmentProximal type (large cell, rhabdoid features)
- 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: Sarcomas (soft tissue, bone, GIST), Osteosarcoma, Ewing sarcoma, Rhabdomyosarcoma, Chordoma, Desmoid tumour, Tenosynovial giant cell tumour (TGCT), Vascular tumours (angiosarcoma, epithelioid haemangioendothelioma, kaposiform haemangioendothelioma)
Under one case per million people per year; the distal type peaks in young adults aged 20 to 40, the proximal type in older adults.
- 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.
Wide resection with negative margins plus radiotherapy for large, deep or close-margin tumours; lymph node assessment considered because of nodal spread.
Tazemetostat (accelerated approval 2020, EZH-202) or anthracycline-based chemotherapy; clinical trial enrolment encouraged, including EZH-301 (doxorubicin with or without tazemetostat).
Subtypes & biomarkers
top- Distal (classic) type
- Proximal type (large cell, rhabdoid features)
- SMARCB1/INI1 loss by immunohistochemistry (diagnostic)
- CD34 and cytokeratin co-expression
- Regional lymph node status
- Tumour size and depth (proximal vs distal)
Target prevalence in this cancer
- 1970Enzinger describes epithelioid sarcoma
Named for its resemblance to carcinoma and granuloma.
- 2005SMARCB1/INI1 loss recognised
Modena and colleagues link the tumour to SWI/SNF deficiency.
- 2013EZH2 dependency of SMARCB1-deficient cells
Knutson and colleagues, PNAS: EZH2 inhibition kills INI1-negative cells.
- 2020Tazemetostat accelerated approval
FDA, 23 January 2020, based on EZH-202 (Gounder and colleagues, Lancet Oncol 2020).
- 2020EZH-301 confirmatory trial opens
Doxorubicin with or without tazemetostat, first line (NCT04204941).
Open problems, and what is being done about each
Response rate to tazemetostat monotherapy is modest: combinations with doxorubicin (EZH-301) and immunotherapy are being tested.
Confirmatory evidence for the accelerated approval is still pending.
Late diagnosis of distal lesions mistaken for warts or granulomas.
and how the field plans to fix it →What is being done about thisFinding cancer earlierAvailable now- 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
In trialsIdeas and roadmaps- 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.
Proximal-type disease remains chemoresistant and rapidly progressive.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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.
Expert centres
topCentres linked to this cancer in OnCo
- via Sentinel lymph node biopsy
- Aarhus University HospitalAarhus, DKvia IMRT / IGRT (modern external beam)
- Alliance for Clinical Trials in OncologyChicago, IL, USvia Sentinel lymph node biopsy
- American Society for Radiation OncologyArlington, VA, USvia IMRT / IGRT (modern external beam)
- Centre Antoine LacassagneNice, FRvia IMRT / IGRT (modern external beam)
- Centre Oscar LambretLille, FRvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Comprehensive Cancer Center Freiburg (CCCF)Freiburg im Breisgau, DEvia IMRT / IGRT (modern external beam)
- European Society for Radiotherapy and OncologyBrussels, BEvia IMRT / IGRT (modern external beam)
- European Society of Surgical OncologyBrussels, BEvia Sentinel lymph node biopsy
- Geneva University Hospitals (HUG)Geneva, CHvia IMRT / IGRT (modern external beam)
- Groote Schuur Hospital / University of Cape TownCape Town, ZAvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Hacettepe University Cancer InstituteAnkara, TRvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Ho Chi Minh City Oncology HospitalHo Chi Minh City, VNvia IMRT / IGRT (modern external beam)
- Hokkaido University HospitalSapporo, JPvia IMRT / IGRT (modern external beam)
- Hunan Cancer HospitalChangsha, CNvia IMRT / IGRT (modern external beam)
- Institut BergoniéBordeaux, FRvia IMRT / IGRT (modern external beam)
- Institut National d'Oncologie, RabatRabat, MAvia IMRT / IGRT (modern external beam)
- Institut Salah AzaïezTunis, TNvia IMRT / IGRT (modern external beam)
- Institute of Oncology LjubljanaLjubljana, SIvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- International Extranodal Lymphoma Study GroupBellinzona, CHvia IMRT / IGRT (modern external beam)
- IRCCS Humanitas Research HospitalRozzano (Milan), ITvia IMRT / IGRT (modern external beam)
- Istanbul University Institute of OncologyIstanbul, TRvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Juravinski Cancer Centre / Escarpment Cancer Research InstituteHamilton, ON, CAvia IMRT / IGRT (modern external beam)
- Keio University HospitalTokyo, JPvia Sentinel lymph node biopsy
- Kenyatta National HospitalNairobi, KEvia IMRT / IGRT (modern external beam)
- Korle Bu Teaching HospitalAccra, GHvia IMRT / IGRT (modern external beam)
- Lagos University Teaching HospitalLagos, NGvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- National Institute of Oncology, HungaryBudapest, HUvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- NSABP FoundationPittsburgh, PA, USvia Sentinel lymph node biopsy
- Ocean Road Cancer InstituteDar es Salaam, TZvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Rajiv Gandhi Cancer Institute and Research CentreNew Delhi, INvia IMRT / IGRT (modern external beam)
- Rambam Health Care CampusHaifa, ILvia IMRT / IGRT (modern external beam)
- Rigshospitalet – Copenhagen University HospitalCopenhagen, DKvia IMRT / IGRT (modern external beam)
- Royal Adelaide HospitalAdelaide, AUvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Siriraj Hospital, Mahidol UniversityBangkok, THvia IMRT / IGRT (modern external beam)
- Society of Surgical OncologyRosemont, IL, USvia Sentinel lymph node biopsy
- Tata Medical Center, KolkataKolkata, INvia IMRT / IGRT (modern external beam)
- Tawam HospitalAl Ain, AEvia IMRT / IGRT (modern external beam)
- Tel Aviv Sourasky Medical CenterTel Aviv, ILvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- TROG Cancer ResearchNewcastle, NSW, AUvia IMRT / IGRT (modern external beam)
- UMC Utrecht Cancer CenterUtrecht, NLvia IMRT / IGRT (modern external beam)
- University of Malaya Medical CentreKuala Lumpur, MYvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Velindre Cancer CentreCardiff, GBvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Zhejiang Cancer HospitalHangzhou, CNvia IMRT / IGRT (modern external beam)
Questions to ask
topQuestions to ask your oncologist about Epithelioid 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 SMARCB1/INI1 loss by immunohistochemistry, CD34 and cytokeratin co-expression, Regional lymph node status, Tumour size and depth), 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 Distaltype, Proximal type.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Localised
- For my situation (localised), which of the standard options do you recommend and why?Why: Guideline options include: Wide resection with negative margins plus radiotherapy for large, deep or close-margin tumours; lymph node assessment considered because of nodal spread.
Advanced or metastatic
- For my situation (advanced or metastatic), which of the standard options do you recommend and why?Why: Guideline options include: Tazemetostat (accelerated approval 2020, EZH-202) or anthracycline-based chemotherapy; clinical trial enrolment encouraged, including EZH-301 (doxorubicin with or without tazemetostat).
- Am I a candidate for Tazemetostat, Doxorubicin, Ifosfamide, 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 Tazemetostat?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 “Response rate to tazemetostat monotherapy is modest: combinations with doxorubicin (EZH-301) and immunotherapy are being tested”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Confirmatory evidence for the accelerated approval is still pending”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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
6targets
1drugs
3companies
1pathways
2terms
2bottlenecks
1Latest papers
topQuery for this cancer: (TITLE:"Epithelioid sarcoma" OR ABSTRACT:"Epithelioid sarcoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Epithelioid sarcoma, not a curated reading list.
Pages like this
not linked directly; found by shared links- CancerDesmoid tumour
Shares Limb-salvage surgery and endoprosthetic reconstruction, Rare cancers, Doxorubicin, Rare and paediatric cancers without markets and the tags nci-coverage, rare, sarcoma.
- CancerChordoma
Shares Tazemetostat, SWI/SNF chromatin remodelling, EZH2, Rare cancers and the tags nci-coverage, rare, sarcoma.
- CancerTenosynovial giant cell tumour (TGCT)
Shares Limb-salvage surgery and endoprosthetic reconstruction, Rare cancers, Rare and paediatric cancers without markets and the tags nci-coverage, rare, sarcoma.
- CancerVascular tumours (angiosarcoma, epithelioid haemangioendothelioma, kaposiform haemangioendothelioma)
Shares Rare cancers, Doxorubicin, Rare and paediatric cancers without markets, IMRT / IGRT (modern external beam) and the tags nci-coverage, rare, sarcoma.
- CancerNUT carcinoma (midline carcinoma with NUTM1 rearrangement)
Shares Ifosfamide, Rare cancers, Epigenetic reprogramming, Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET) and the tags nci-coverage, rare.
- CancerUterine sarcoma
Shares Rare cancers, Doxorubicin, Rare and paediatric cancers without markets, Cytotoxic chemotherapy and the tags nci-coverage, rare, sarcoma.
- CancerInflammatory myofibroblastic tumour (IMT)
Shares Limb-salvage surgery and endoprosthetic reconstruction, Rare cancers, Rare and paediatric cancers without markets and the tags nci-coverage, rare, sarcoma.
- CancerNasal cavity and paranasal sinus cancers (including esthesioneuroblastoma)
Shares SWI/SNF chromatin remodelling, Rare cancers, Rare and paediatric cancers without markets, IMRT / IGRT (modern external beam) and the tags nci-coverage, rare.