Mismatch-repair-deficient endometrial cancer: the decisions you may face
5 treatment settings, 4 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.
Diagnosis and hereditary risk
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.
A test of the DNA you were born with, to find inherited risk genes such as BRCA or Lynch syndrome.
- Actionable for patient and relatives
- Cheap
Histopathology means looking at cancer cells under a microscope, and immunohistochemistry stains them for specific proteins. Together they are still the foundation of every diagnosis.
- Cheap, fast, universal
- Companion diagnostic for most targeted drugs
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- VUS burden
- Uptake and counselling capacity
- Subjective scoring
- Single-site sampling misses heterogeneity
- Between Germline (hereditary) testing and Histopathology & immunohistochemistry, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- For my situation (diagnosis and hereditary risk), which of the standard options do you recommend and why?Why: Guideline options include: 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.
Add these to your appointment list, or take the full question set for this cancer.
Early stage after surgery
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).
Brachytherapy places a radioactive source directly inside or next to the tumour.
- Highest conformality
- Short treatment
IMRT and IGRT shape the radiation beam to the tumour's outline from multiple angles and check the patient's position with a scan before every session, so surrounding organs receive less dose. Fewer, larger doses are now standard in breast and prostate cancer, but a low-dose bath still spreads across normal tissue.
- Conformal dose, fewer side effects
- Hypofractionation saves visits
- High-risk early or stage III endometrial cancer after surgery: chemoradiation + 4 cycles chemotherapy vs pelvic radiotherapy alone
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- 5-year OS 81.4% vs 76.1% (HR 0.70); benefit concentrated in p53-abnormal disease.
Overall survival at 5 years (%): Chemoradiation + chemotherapy 81.4 (n=330) vs Radiotherapy alone 76.1 (n=330) · HR 0.7 · source
- Invasive
- Declining expertise in some regions
- Low-dose bath to normal tissue
- Motion management
- Between Brachytherapy and IMRT / IGRT (modern external beam), which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in PORTEC-3, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- For my situation (early stage after surgery), which of the standard options do you recommend and why?Why: Guideline options include: 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).
- How do the results of PORTEC-3 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Advanced or recurrent, first line
Carboplatin-paclitaxel with dostarlimab (RUBY) or pembrolizumab (NRG-GY018), continued as maintenance; durvalumab (DUO-E) is an alternative.
Dostarlimab is a PD-1 blocker famous for making rectal cancer disappear without surgery in every patient with a mismatch-repair-deficient tumour.
Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.
A PD-L1 blocker that became standard after chemoradiation for stage III lung cancer, and now in bladder, biliary, and gastric cancers.
Carboplatin is a platinum chemotherapy that crosslinks DNA; it is part of the standard pre-surgery regimen for triple-negative breast cancer.
A microtubule poison discovered in the Pacific yew tree, among the most used chemotherapies in breast, lung, and ovarian cancer.
- Primary advanced (stage III-IV) or first recurrent endometrial cancer: dostarlimab + carboplatin-paclitaxel, then dostarlimab up to 3 years, vs chemotherapy
OS 44.6 vs 28.2 months overall (HR 0.69); dMMR PFS HR 0.28.
Progression-free survival at 24 months (dMMR/MSI-H) (%): Dostarlimab + chemo 61.4 vs Placebo + chemo 15.7 · HR 0.28 · source - Advanced or recurrent endometrial cancer: pembrolizumab + carboplatin-paclitaxel then pembrolizumab maintenance vs chemotherapy, analysed by MMR status
PFS HR 0.30 (dMMR), 0.54 (pMMR).
- Newly diagnosed advanced or recurrent endometrial cancer: chemotherapy + durvalumab, then durvalumab ± olaparib maintenance, vs chemotherapy
PFS HR 0.42 (dMMR, durvalumab); 0.57 (pMMR, durvalumab + olaparib).
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients | 8% | - |
| Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 3.4% | - |
| Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 1.7% | - |
| Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 0.7% | - |
- No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Pneumonitis (any cause, PACIFIC) · vs 12.8% placebo; 1.1% fatal | 18.3% | - |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Dose by Calvert formula using GFR (see the calculators).
- Between Dostarlimab, Pembrolizumab, Durvalumab and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in RUBY / ENGOT-EN6 / GOG-3031 and NRG-GY018 / KEYNOTE-868, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Pembrolizumab or Durvalumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- For my situation (advanced or recurrent, first line), which of the standard options do you recommend and why?Why: Guideline options include: Carboplatin-paclitaxel with dostarlimab (RUBY) or pembrolizumab (NRG-GY018), continued as maintenance; durvalumab (DUO-E) is an alternative.
- Am I a candidate for Dostarlimab, Pembrolizumab, Durvalumab or related drugs, 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 RUBY / ENGOT-EN6 / GOG-3031 and NRG-GY018 / KEYNOTE-868 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Recurrent after chemotherapy without prior immunotherapy
Single-agent dostarlimab or pembrolizumab, with durable responses in a large minority.
Dostarlimab is a PD-1 blocker famous for making rectal cancer disappear without surgery in every patient with a mismatch-repair-deficient tumour.
Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.
Immune checkpoint inhibitors are antibodies against CTLA-4, PD-1 or PD-L1 that release the brakes on T cells so they attack the cancer. They are approved in more than 20 tumour types and produce lasting, sometimes curative responses that chemotherapy rarely does, but most patients do not respond and autoimmune side effects are the cost.
- Durable, sometimes curative responses
- Broad applicability
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients | 8% | - |
| Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 3.4% | - |
| Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 1.7% | - |
| Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 0.7% | - |
- No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Most patients do not respond
- Autoimmune toxicity
- Biomarkers are imperfect
- Between Dostarlimab, Pembrolizumab and Immune checkpoint inhibitors, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- Which side effects of Pembrolizumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- For my situation (recurrent after chemotherapy without prior immunotherapy), which of the standard options do you recommend and why?Why: Guideline options include: Single-agent dostarlimab or pembrolizumab, with durable responses in a large minority.
- Am I a candidate for Dostarlimab, Pembrolizumab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.
Lynch carriers
Annual surveillance from the mid-thirties where offered, aspirin, and risk-reducing hysterectomy with salpingo-oophorectomy after childbearing.
A test of the DNA you were born with, to find inherited risk genes such as BRCA or Lynch syndrome.
- Actionable for patient and relatives
- Cheap
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- VUS burden
- Uptake and counselling capacity
- Is Germline (hereditary) testing the only reasonable path for me, or is there a trial, a different sequence or a wait-and-see option?Why: A single standard does not mean a single choice; timing and trials are decisions too.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- For my situation (lynch carriers), which of the standard options do you recommend and why?Why: Guideline options include: Annual surveillance from the mid-thirties where offered, aspirin, and risk-reducing hysterectomy with salpingo-oophorectomy after childbearing.
Add these to your appointment list, or take the full question set for this cancer.