Undifferentiated pleomorphic sarcoma (UPS)
Undifferentiated pleomorphic sarcoma is the diagnosis for a high-grade soft tissue sarcoma whose cells show no recognisable line of differentiation. It is treated with surgery and radiotherapy, with doxorubicin-based chemotherapy for high-risk or spread disease, and it is one of the few sarcomas in which the immunotherapy drug pembrolizumab has clear activity.
Overview
Undifferentiated pleomorphic sarcoma is a diagnosis of exclusion: a genomically complex, high-grade sarcoma with no line of differentiation on histology, immunohistochemistry or molecular testing. It replaced the older label malignant fibrous histiocytoma once many such tumours were reclassified as dedifferentiated liposarcoma, myxofibrosarcoma or pleomorphic leiomyosarcoma. It arises mostly in the deep soft tissues of the limbs in people over 60, less often in the retroperitoneum, and its genome shows widespread copy number change with TP53, RB1, CDKN2A and ATRX loss rather than a driver fusion.
Localised disease is treated with wide resection and radiotherapy, given preoperatively or postoperatively, following the principles established for extremity sarcoma. In the Italian Sarcoma Group ISG-STS 1001 trial, three cycles of neoadjuvant epirubicin and ifosfamide improved relapse-free and overall survival in high-risk limb and trunk sarcomas, a benefit driven partly by the UPS group, and full-dose anthracycline-ifosfamide is offered to fit patients with large, deep, high-grade tumours. Advanced disease is treated with doxorubicin alone or with ifosfamide, gemcitabine-docetaxel, trabectedin or pazopanib.
UPS stands out among sarcomas for immunotherapy: in the SARC028 phase 2 trial pembrolizumab produced objective responses in undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma but almost none in leiomyosarcoma or synovial sarcoma, and the randomised SU2C-SARC032 trial found that pembrolizumab added to preoperative radiotherapy and surgery improved disease-free survival in stage III UPS and dedifferentiated liposarcoma of the limbs. Tertiary lymphoid structures and B-cell-rich immune classes predict who benefits.
State of the art
- SARC028 identified UPS as the sarcoma with the clearest response to PD-1 blockade.
- SU2C-SARC032 showed pembrolizumab with preoperative radiotherapy improves disease-free survival in stage III limb UPS and dedifferentiated liposarcoma.
- Immune classification by B-cell signatures is being tested to select patients for immunotherapy.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowBowel perforation
Sudden severe abdominal pain, a hard or very tender abdomen, or abdominal pain with vomiting and fever. Boxed warning for gastrointestinal perforation on bevacizumab.
- Emergency services nowFainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
- Check before combiningFood and drink: Doxorubicin
Cumulative dose: risk rises steeply above 400-550 mg/m² (see the anthracycline calculator).
- Check before combiningFood and drink: Pazopanib
Take on an empty stomach (1 hour before or 2 hours after food).
See all on the product pages:DocetaxelDoxorubicinGemcitabineIfosfamidePazopanibPembrolizumabTrabectedin·Printable cards in the navigator
Anatomy and lymph node drainage
- Metaphysis, near the growth plate (osteosarcoma)
- Shaft (Ewing sarcoma)
- Deep soft tissue compartment
- Skeletal muscle (rhabdomyosarcoma)
- Neurovascular bundle (limb salvage decision)
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)Undifferentiated round cell and spindle cell sarcomas (separate WHO categories, fusion-defined)
- Deep soft tissue compartmentUndifferentiated pleomorphic sarcoma of the limbs (commonest) · Undifferentiated pleomorphic sarcoma of the trunk and retroperitoneum · Radiation-associated undifferentiated sarcoma · Undifferentiated round cell and spindle cell sarcomas (separate WHO categories, fusion-defined)
- Skeletal muscle (rhabdomyosarcoma)Undifferentiated pleomorphic sarcoma of the limbs (commonest) · Undifferentiated pleomorphic sarcoma of the trunk and retroperitoneum · Undifferentiated round cell and spindle cell sarcomas (separate WHO categories, fusion-defined)
- 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: Leiomyosarcoma, Liposarcoma, Synovial sarcoma, Sarcomas (soft tissue, bone, GIST), Osteosarcoma, Ewing sarcoma, Rhabdomyosarcoma, Chordoma, Desmoid tumour, Tenosynovial giant cell tumour (TGCT), Epithelioid sarcoma, Vascular tumours (angiosarcoma, epithelioid haemangioendothelioma, kaposiform haemangioendothelioma), Chondrosarcoma, Angiosarcoma, Myxofibrosarcoma, Alveolar soft part sarcoma, Perivascular epithelioid cell tumour (PEComa), Epithelioid haemangioendothelioma, Malignant peripheral nerve sheath tumour (MPNST), Retroperitoneal sarcoma, Soft tissue sarcoma of the extremity (localised and advanced)
One of the commonest soft tissue sarcomas of older adults, usually a deep, fast-growing mass in the thigh or upper arm; about a third of patients with high-grade limb tumours develop lung metastases despite surgery and radiotherapy.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Wide resection with preoperative or postoperative radiotherapy; neoadjuvant anthracycline-ifosfamide for large, deep, high-grade tumours in fit patients (ISG-STS 1001).
Doxorubicin alone or doxorubicin plus ifosfamide (EORTC 62012) when response matters.
Gemcitabine-docetaxel, trabectedin, pazopanib; pembrolizumab in trials or off label after SARC028.
Subtypes & biomarkers
top- Undifferentiated pleomorphic sarcoma of the limbs (commonest)
- Undifferentiated pleomorphic sarcoma of the trunk and retroperitoneum
- Radiation-associated undifferentiated sarcoma
- Undifferentiated round cell and spindle cell sarcomas (separate WHO categories, fusion-defined)
- FNCLCC grade, size and depth (risk)
- Exclusion of specific differentiation by immunohistochemistry and molecular testing
- TP53, RB1, CDKN2A and ATRX alterations
- Tertiary lymphoid structures and B-cell-rich immune class (immunotherapy response)
How often this target appears
- 1964O'Brien and Stout describe malignant fibrous histiocytoma
- 2002WHO abandons malignant fibrous histiocytoma as a diagnosis in favour of undifferentiated pleomorphic sarcoma
- 2014EORTC 62012: doxorubicin plus ifosfamide improves response and progression-free but not overall survival
- 2017ISG-STS 1001: neoadjuvant epirubicin-ifosfamide improves survival in high-risk limb sarcoma
- 2017SARC028: pembrolizumab responses concentrated in UPS and dedifferentiated liposarcoma
- 2024SU2C-SARC032: pembrolizumab plus preoperative radiotherapy improves disease-free survival
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 9 changes by month →- 2026-09-17This recordUndifferentiated pleomorphic sarcoma (UPS)Facts on this page last checked
When this page itself was last checked or edited.
- 2024MilestonePembrolizumabSU2C-SARC032: pembrolizumab plus preoperative radiotherapy improves disease-free survival
A milestone in how this cancer is treated.
- 2017Trial resultISG-STS 1001ISG-STS 1001 reported
Standard arm DFS HR ~0.
- 2017MilestoneISG-STS 1001ISG-STS 1001: neoadjuvant epirubicin-ifosfamide improves survival in high-risk limb sarcoma
A milestone in how this cancer is treated.
- 2017MilestonePembrolizumabSARC028: pembrolizumab responses concentrated in UPS and dedifferentiated liposarcoma
A milestone in how this cancer is treated.
- 2014Trial resultEORTC 62012EORTC 62012 reported
Median OS 14.
What is in development for Undifferentiated pleomorphic sarcoma (UPS), drawn from the whole corpus: 2 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Trials reported · 2
- ISG-STS 1001 · phase 3 · 2017 · positive
- EORTC 62012 · phase 3 · 2014 · completed
Open problems and what is being done
No molecular driver to target; the diagnosis is defined by what the tumour is not.
A third of high-grade limb tumours still metastasise to the lungs.
and how the field plans to fix it →What is being done about thisAdvanced and metastatic diseaseAvailable now- DocetaxelApproved
- IMRT / IGRT (modern external beam)Standard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Atlas of advanced disease · Invasion and metastasis.
Which patients gain from neoadjuvant chemotherapy versus immunotherapy is not settled.
Trials
topTrials recruiting now
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.
Landmark trials
Expert centres
topExpert centres
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Amsterdam · cancer center | Netherlands | none recorded | 0 | 1,451 | 25,873 | #45 | |
Wuhan · hospital | China | none recorded | 0 | 2,478 | 31,527 | - | |
Utrecht · cancer center | Netherlands | none recorded | 0 | 1,422 | 20,323 | - | |
Beijing · cancer center | China | none recorded | 0 | 1,344 | 18,195 | - | |
Leiden · university | Netherlands | none recorded | 0 | 1,245 | 16,125 | - | |
Tianjin · cancer center | China | none recorded | 0 | 1,219 | 11,455 | - | |
Hangzhou · cancer center | China | none recorded | 0 | 1,219 | 17,635 | - | |
Lyon · cancer center | France | none recorded | 0 | 1,071 | 14,301 | - | |
Rozzano (Milan) · hospital | Italy | none recorded | 0 | 1,031 | 10,720 | - | |
Zhengzhou · cancer center | China | none recorded | 0 | 970 | 12,409 | - | |
Padua · cancer center | Italy | none recorded | 0 | 962 | 12,326 | - | |
Naples · cancer center | Italy | none recorded | 0 | 961 | 15,028 | - | |
Changsha · cancer center | China | none recorded | 0 | 930 | 14,477 | - | |
Jinan · cancer center | China | none recorded | 0 | 920 | 7,804 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Undifferentiated pleomorphic sarcoma but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Undifferentiated pleomorphic 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 FNCLCC grade, size and depth, Exclusion of specific differentiation by immunohistochemistry and molecular testing, TP53, RB1, CDKN2A and ATRX alterations, Tertiary lymphoid structures and B-cell-rich immune class), 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 Undifferentiated pleomorphic sarcoma of the limbs, Undifferentiated pleomorphic sarcoma of the trunk and retroperitoneum, Radiation-associated undifferentiated sarcoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Localised, limb or trunk
- For my situation (localised, limb or trunk), which of the standard options do you recommend and why?Why: Guideline options include: Wide resection with preoperative or postoperative radiotherapy; neoadjuvant anthracycline-ifosfamide for large, deep, high-grade tumours in fit patients (ISG-STS 1001).
- Am I a candidate for Doxorubicin, Ifosfamide, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ISG-STS 1001 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Advanced, first line
- For my situation (advanced, first line), which of the standard options do you recommend and why?Why: Guideline options include: Doxorubicin alone or doxorubicin plus ifosfamide (EORTC 62012) when response matters.
- Am I a candidate for Doxorubicin, Ifosfamide, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of EORTC 62012 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Later lines
- For my situation (later lines), which of the standard options do you recommend and why?Why: Guideline options include: Gemcitabine-docetaxel, trabectedin, pazopanib; pembrolizumab in trials or off label after SARC028.
- Am I a candidate for Gemcitabine, Docetaxel, Trabectedin 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 Pembrolizumab, Immune checkpoint inhibitors, ISG-STS 1001?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 “No molecular driver to target; the diagnosis is defined by what the tumour is not”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “A third of high-grade limb tumours still metastasise to the lungs”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Undifferentiated pleomorphic sarcoma, then print the one-page appointment sheet with room for the answers.
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
8targets
3drugs
7companies
5terms
1trials
2Latest papers
topQuery for this cancer: (TITLE:"Undifferentiated pleomorphic sarcoma" OR ABSTRACT:"Undifferentiated pleomorphic sarcoma" OR TITLE:"UPS" OR ABSTRACT:"UPS" OR TITLE:"Malignant fibrous histiocytoma historic" OR ABSTRACT:"Malignant fibrous histiocytoma historic" OR TITLE:"MFH" OR ABSTRACT:"MFH" OR TITLE:"Pleomorphic sarcoma, not otherwise specified" OR ABSTRACT:"Pleomorphic sarcoma, not otherwise specified") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Undifferentiated pleomorphic sarcoma (UPS), not a curated reading list.
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