{"entity":{"id":"uterine-carcinosarcoma","kind":"cancer","name":"Uterine carcinosarcoma","aka":["Malignant mixed Mullerian tumour","MMMT","Endometrial carcinosarcoma"],"tldr":"Uterine carcinosarcoma is a two-faced cancer with a carcinoma part and a sarcoma-like part that both come from the same faulty epithelial cell. It is treated as a high-grade endometrial cancer, with surgery, carboplatin-paclitaxel and often radiotherapy, and its frequent HER2 expression is opening a route to antibody-drug conjugates.","summary":"Carcinosarcoma contains both a carcinomatous component, usually serous or high-grade endometrioid, and a sarcomatous component, which may resemble fibrosarcoma, leiomyosarcoma or heterologous tissue such as cartilage or skeletal muscle. Sequencing shows that both components share the same TP53, PIK3CA, FBXW7 and PPP2R1A mutations, so the tumour is a carcinoma that has undergone epithelial-to-mesenchymal transition rather than a true sarcoma, and it is classified and staged as an endometrial carcinoma. Almost all are p53-abnormal; a minority are mismatch-repair deficient and a few POLE-ultramutated, and HER2 is expressed or amplified in a substantial minority. Patients are older than average, tamoxifen exposure and prior pelvic radiotherapy are risk factors, and the tumour often presents as a polypoid mass protruding through the cervix.\n\nSurgery with hysterectomy, salpingo-oophorectomy, nodal assessment and omental sampling is followed by chemotherapy for almost every stage. Ifosfamide-paclitaxel had been the standard after GOG-0161, but GOG-0261 showed carboplatin-paclitaxel non-inferior and less toxic, and it is now the regimen of choice. Radiotherapy improves local control and is added for pelvic-confined disease with risk factors, and the ESGO/ESTRO/ESP guideline treats carcinosarcoma as p53-abnormal high-risk disease for adjuvant decisions. RUBY included carcinosarcoma among its histologies, so dostarlimab with chemotherapy is an option in advanced disease, with the largest benefit in the mismatch-repair-deficient minority.\n\nHER2 is the most promising target. The Japanese STATICE trial gave trastuzumab deruxtecan to HER2-expressing carcinosarcoma and reported responses in about half of patients, and DESTINY-PanTumor02 included carcinosarcoma in its endometrial cohort, which underpins the tumour-agnostic approval for HER2 3+ tumours. Trials of WEE1 and ATR inhibitors exploit the p53-null cell cycle, and PARP inhibition is being tested on the same homologous recombination logic as in ovarian cancer. Rarity keeps carcinosarcoma out of most dedicated randomised trials, so its evidence base is borrowed from serous endometrial cancer.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Uterine_carcinosarcoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Uterine_carcinosarcoma"}],"tags":["subtype-page"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"gynaecologic","burden":"About five percent of uterine cancers but a far larger share of deaths; most patients are older women, half present with disease beyond the uterus, and even stage I tumours recur in a third of cases.","subtypes":["Homologous carcinosarcoma (sarcoma element resembles uterine tissue)","Heterologous carcinosarcoma (cartilage, bone or skeletal muscle elements)","Serous-type carcinoma component (most common, p53-abnormal)","HER2-expressing carcinosarcoma (trastuzumab deruxtecan)","Mismatch-repair-deficient carcinosarcoma (minority, immunotherapy-responsive)","Stage I carcinosarcoma (adjuvant chemotherapy with or without radiotherapy)"],"biomarkers":["p53 immunohistochemistry (abnormal in most)","HER2 immunohistochemistry and in situ hybridisation","MMR immunohistochemistry (deficient in a minority)","POLE (rare, favourable)","Percentage of sarcomatous component and heterologous elements","CA-125"],"standardOfCare":[{"setting":"Surgery","approach":"Hysterectomy with bilateral salpingo-oophorectomy, sentinel node mapping or lymphadenectomy, and omental sampling.","refs":["hysterectomy","sentinel-node","robotic-surgery"]},{"setting":"Adjuvant, all stages","approach":"Carboplatin-paclitaxel (GOG-0261), with pelvic radiotherapy and vaginal brachytherapy for stage I to III disease with risk factors; ifosfamide-paclitaxel is the older alternative.","refs":["carboplatin","paclitaxel","ifosfamide","imrt-igrt","brachytherapy","portec-3"]},{"setting":"Advanced or recurrent","approach":"Carboplatin-paclitaxel with dostarlimab (RUBY included carcinosarcoma); trastuzumab deruxtecan for HER2-expressing disease; lenvatinib-pembrolizumab after platinum.","refs":["dostarlimab","ruby","trastuzumab-deruxtecan","destiny-pantumor02","her2","lenvatinib","pembrolizumab"]}],"stateOfArt":["Genomics reclassified carcinosarcoma from sarcoma to a metaplastic carcinoma, so it follows endometrial cancer guidelines.","GOG-0261 replaced ifosfamide-paclitaxel with carboplatin-paclitaxel.","HER2-directed antibody-drug conjugates are the first targeted therapy to show activity."],"history":[{"year":2007,"title":"GOG-0161: ifosfamide-paclitaxel improves survival over ifosfamide alone","refs":["ifosfamide","paclitaxel"]},{"year":2014,"title":"WHO classifies carcinosarcoma as a metaplastic carcinoma rather than a sarcoma","refs":[]},{"year":2017,"title":"TCGA sequencing confirms a shared clonal origin of both components with frequent TP53 mutation","refs":["tp53"]},{"year":2022,"title":"GOG-0261: carboplatin-paclitaxel non-inferior to ifosfamide-paclitaxel","refs":["carboplatin","paclitaxel"]},{"year":2023,"title":"STATICE: trastuzumab deruxtecan active in HER2-expressing carcinosarcoma","refs":["trastuzumab-deruxtecan"]}],"pipeline":["trastuzumab-deruxtecan","dostarlimab","wee1","atr","idea-her2-adc-serous-endometrial"],"openProblems":["No dedicated randomised trials for a tumour that behaves worse than the serous cancers it is grouped with.","Whether the sarcomatous component needs different drugs.","High relapse rate after apparently complete treatment of stage I disease."],"parent":"endometrial"},"route":"/cancers/uterine-carcinosarcoma/","neighbours":{"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"ifosfamide","kind":"drug","name":"Ifosfamide","route":"/drugs/ifosfamide/"},{"id":"lenvatinib","kind":"drug","name":"Lenvatinib","route":"/drugs/lenvatinib/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"target":[{"id":"atr","kind":"target","name":"ATR","route":"/targets/atr/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"},{"id":"wee1","kind":"target","name":"WEE1","route":"/targets/wee1/"}],"idea":[{"id":"idea-her2-adc-serous-endometrial","kind":"idea","name":"HER2 ADCs as standard for HER2-positive serous endometrial cancer","route":"/ideas/idea-her2-adc-serous-endometrial/"}],"term":[{"id":"hysterectomy","kind":"term","name":"Hysterectomy","route":"/terms/hysterectomy/"}],"technology":[{"id":"brachytherapy","kind":"technology","name":"Brachytherapy","route":"/technologies/brachytherapy/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"robotic-surgery","kind":"technology","name":"Robotic & minimally invasive surgery","route":"/technologies/robotic-surgery/"},{"id":"sentinel-node","kind":"technology","name":"Sentinel lymph node biopsy","route":"/technologies/sentinel-node/"}],"trial":[{"id":"destiny-pantumor02","kind":"trial","name":"DESTINY-PanTumor02","route":"/trials/destiny-pantumor02/"},{"id":"portec-3","kind":"trial","name":"PORTEC-3","route":"/trials/portec-3/"},{"id":"ruby","kind":"trial","name":"RUBY / ENGOT-EN6 / GOG-3031","route":"/trials/ruby/"}],"cancer":[{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"}]}}