Loading
Mismatch-repair-deficient endometrial cancer has lost the machinery that corrects copying errors in DNA, so it accumulates thousands of mutations that make it visible to the immune system. Adding dostarlimab or pembrolizumab to chemotherapy in advanced disease cut the risk of progression by about seventy percent, and many patients remain in remission years later.
Loss of MLH1, PMS2, MSH2 or MSH6 on immunohistochemistry, or microsatellite instability on a molecular test, defines this class. In most tumours the cause is methylation of the MLH1 promoter; in a minority it is a germline mutation in a mismatch-repair gene, which is Lynch syndrome, so every deficient tumour without MLH1 methylation should prompt germline testing and family cascade testing. Mismatch-repair-deficient tumours are usually endometrioid, often high grade, with abundant tumour-infiltrating lymphocytes, and they carry an intermediate prognosis at early stage. The class has the same recurrence risk as no specific molecular profile after adjuvant radiotherapy, and PORTEC-3 found no benefit from adding chemotherapy in this group.
The mutational load makes these tumours the most immunotherapy-responsive solid cancers outside melanoma. Pembrolizumab's tumour-agnostic approval for mismatch-repair-deficient tumours in 2017 and dostarlimab's approval after the GARNET trial in 2021 established single-agent checkpoint inhibition after chemotherapy. RUBY then moved immunotherapy to the first line: dostarlimab with carboplatin-paclitaxel raised progression-free survival at two years from 15.7 to 61.4 percent in the deficient population, with a hazard ratio of 0.28. NRG-GY018 found the same with pembrolizumab, a hazard ratio of 0.30 for progression in deficient tumours, and DUO-E with durvalumab a hazard ratio of 0.42. Both dostarlimab and pembrolizumab gained approvals with chemotherapy in 2023 and 2024.
The next question is whether chemotherapy is needed at all. KEYNOTE-C93 compares pembrolizumab alone with platinum doublet chemotherapy as first-line treatment of deficient advanced disease. In the adjuvant setting KEYNOTE-B21 did not improve disease-free survival overall when pembrolizumab was added to chemotherapy after surgery, but the mismatch-repair-deficient subgroup appeared to benefit, and RAINBO's MMRd-GREEN trial randomises deficient stage II to III tumours to radiotherapy with or without durvalumab. Prevention in Lynch carriers rests on surveillance, aspirin and risk-reducing hysterectomy once childbearing is complete, and frameshift neoantigen vaccines are in early trials.
About a quarter to three in ten endometrial cancers, the largest molecular class after no specific molecular profile; most are sporadic and caused by MLH1 promoter methylation, and about three percent of all endometrial cancers arise in Lynch syndrome carriers.
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.
Same organ: Adenosquamous carcinoma of the cervix, Small cell neuroendocrine carcinoma of the cervix, Bartholin gland carcinoma, Vulvar melanoma, Vaginal melanoma, High-grade serous ovarian cancer, Low-grade serous ovarian cancer, Clear cell ovarian cancer, Mucinous ovarian cancer, Adult granulosa cell tumour of the ovary, Ovarian cancer, Endometrial cancer, Cervical cancer, Vulvar cancer, Gestational trophoblastic neoplasia, Uterine sarcoma, Vaginal cancer, POLE-ultramutated endometrial cancer, p53-abnormal endometrial cancer, including uterine serous carcinoma, Endometrial cancer with no specific molecular profile, Advanced or recurrent endometrial cancer, Uterine carcinosarcoma, Early cervical cancer and fertility-sparing surgery, Locally advanced cervical cancer, Recurrent or metastatic cervical cancer, Platinum-sensitive ovarian cancer, Platinum-resistant ovarian cancer, HPV-associated vulvar squamous cell carcinoma, HPV-independent vulvar squamous cell carcinoma (p53-mutant), Vaginal squamous cell carcinoma (HPV-associated), Vaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma), Low-risk gestational trophoblastic neoplasia (FIGO score 0 to 6), High-risk gestational trophoblastic neoplasia (FIGO score 7 or more, including ultra-high-risk), Placental-site trophoblastic tumour and epithelioid trophoblastic tumour
Universal MMR immunohistochemistry on every endometrial cancer; MLH1 methylation testing on MLH1-deficient tumours; germline testing and cascade testing of relatives when methylation is absent.
Adjuvant therapy by stage and risk factors as for no specific molecular profile: vaginal brachytherapy for intermediate risk, pelvic radiotherapy for high-intermediate risk; chemotherapy adds little (PORTEC-3).
Carboplatin-paclitaxel with dostarlimab (RUBY) or pembrolizumab (NRG-GY018), continued as maintenance; durvalumab (DUO-E) is an alternative.
Single-agent dostarlimab or pembrolizumab, with durable responses in a large minority.
Annual surveillance from the mid-thirties where offered, aspirin, and risk-reducing hysterectomy with salpingo-oophorectomy after childbearing.
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.
Together with RUBY, this trial made chemo-immunotherapy the first-line standard for advanced endometrial cancer in both molecular groups, with the largest effect in mismatch repair-deficient tumours.
Women with newly diagnosed advanced or recurrent endometrial cancer should receive a PD-1 antibody (dostarlimab or pembrolizumab) with their chemotherapy, and mismatch repair testing is now essential because women with dMMR tumours gain a very large and durable benefit. The gain in mismatch-repair-proficient tumours is real but smaller, and molecular classification (POLE, p53, MMR) is increasingly used to decide who benefits most.
Dostarlimab was approved for previously treated mismatch repair-deficient endometrial cancer on these data, before moving into first-line combination in RUBY.
Molecular class is now a predictive factor for adjuvant therapy: chemotherapy for p53-abnormal disease, de-escalation for POLE-mutated tumours, and trials of immunotherapy for mismatch repair-deficient disease.
Molecular classification of every endometrial cancer, now embedded in the WHO classification and the ESGO/ESTRO/ESP guideline, rests on ProMisE; it decides adjuvant therapy and identifies candidates for immunotherapy.
Query for this cancer: (TITLE:"Mismatch-repair-deficient endometrial cancer" OR ABSTRACT:"Mismatch-repair-deficient endometrial cancer" OR TITLE:"dMMR endometrial cancer" OR ABSTRACT:"dMMR endometrial cancer" OR TITLE:"MSI-high endometrial cancer" OR ABSTRACT:"MSI-high endometrial cancer" OR TITLE:"MMRd endometrial cancer" OR ABSTRACT:"MMRd endometrial cancer" OR TITLE:"Lynch-associated endometrial cancer" OR ABSTRACT:"Lynch-associated endometrial cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Mismatch-repair-deficient endometrial cancer, not a curated reading list.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Dose by Calvert formula using GFR (see the calculators).
During chemotherapy a temperature over 37.5 C or below 36 C, shivering, or feeling unwell even with a normal temperature means ringing the hospital's 24-hour line straight away; breathing very fast, confusion, mottled skin or no urine in a day means 999.
Eyebrows and eyelashes usually fall later than scalp hair and come back later, and their absence is felt more than people expect, because they frame the face and keep dust and sweat out of the eyes.
See all on the product pages:CarboplatinDostarlimabDurvalumabPaclitaxel / nab-paclitaxelPembrolizumab·Printable cards in the navigator
Newly diagnosed? Read the first 60 days with Mismatch-repair-deficient endometrial cancer, 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.
Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record.
Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked.