The first 60 days: Endometrial cancer
The gynaecological cancer where immunotherapy has had the biggest impact, guided by molecular classification. Below, week by week, is what OnCo's record of Endometrial cancer says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Endometrial biopsy for postmenopausal bleeding; MRI for myometrial and cervical invasion; molecular classification (p53, MMR IHC, POLE sequencing) on the diagnostic specimen.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- PathologistNamed in the standard of care for: Early, Prevention and hereditary risk, Diagnosis and staging, Early stage surgery and 4 more.
- RadiologistNamed in the standard of care for: Diagnosis and staging.
- SurgeonNamed in the standard of care for: Early, Prevention and hereditary risk, Early stage surgery, Fertility-sparing (grade 1, stage IA, no invasion).
- Medical oncologistNamed in the standard of care for: Early, Advanced/recurrent, Prevention and hereditary risk, Fertility-sparing (grade 1, stage IA, no invasion) and 6 more.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Adjuvant, low and intermediate risk, Adjuvant, high risk (stage III, serous, p53abn, deep invasion grade 3).
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Universal MMR testing of tumours to identify Lynch syndrome; risk-reducing hysterectomy and salpingo-oophorectomy for Lynch carriers after childbearing; levonorgestrel IUD and weight management reduce risk; no screening for average-risk women.
Hysterectomy; adjuvant therapy by molecular class.
Minimally invasive total hysterectomy and bilateral salpingo-oophorectomy with sentinel lymph node mapping (FIRES, SENTOR); omentectomy for serous histology.
Observation (low risk, POLEmut) or vaginal brachytherapy (intermediate risk; PORTEC-2); molecular class may de-escalate (PORTEC-4a).
Chemoradiation plus carboplatin-paclitaxel (PORTEC-3) or chemotherapy alone (GOG-258); pembrolizumab or dostarlimab added for stage III-IV per RUBY/GY018 eligibility.
Chemotherapy + dostarlimab or pembrolizumab; lenvatinib-pembrolizumab; T-DXd if HER2+.
Progestin (oral or IUD) with re-biopsy every 3-6 months; hysterectomy after childbearing.
Carboplatin-paclitaxel plus dostarlimab (RUBY), pembrolizumab (NRG-GY018/KEYNOTE-868), or durvalumab (DUO-E; dMMR in the US), continued as maintenance up to 2-3 years.
Single-agent PD-1 blockade (dostarlimab GARNET, pembrolizumab) if immunotherapy-naive; otherwise chemotherapy or trials.
Trastuzumab with carboplatin-paclitaxel (randomised phase 2) or T-DXd for IHC 3+ after prior therapy.
Lenvatinib + pembrolizumab (KEYNOTE-775) if not previously given immunotherapy; T-DXd if HER2 IHC 3+; chemotherapy (doxorubicin, weekly paclitaxel); hormonal therapy for low-grade ER-positive disease.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example MMR/MSI, POLE, p53, HER2, ER/PR), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include Endometrioid, Serous, Clear-cell.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Early
- For my situation (early), which of the standard options do you recommend and why?Guideline options include: Hysterectomy; adjuvant therapy by molecular class.
Advanced/recurrent
- For my situation (advanced/recurrent), which of the standard options do you recommend and why?Guideline options include: Chemotherapy + dostarlimab or pembrolizumab; lenvatinib-pembrolizumab; T-DXd if HER2+.
- Am I a candidate for Dostarlimab, Pembrolizumab, Trastuzumab deruxtecan, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Prevention and hereditary risk
- For my situation (prevention and hereditary risk), which of the standard options do you recommend and why?Guideline options include: Universal MMR testing of tumours to identify Lynch syndrome; risk-reducing hysterectomy and salpingo-oophorectomy for Lynch carriers after childbearing; levonorgestrel IUD and weight management reduce risk; no screening for average-risk women.
- Am I a candidate for Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD), and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Diagnosis and staging
- For my situation (diagnosis and staging), which of the standard options do you recommend and why?Guideline options include: Endometrial biopsy for postmenopausal bleeding; MRI for myometrial and cervical invasion; molecular classification (p53, MMR IHC, POLE sequencing) on the diagnostic specimen.
Early stage surgery
- For my situation (early stage surgery), which of the standard options do you recommend and why?Guideline options include: Minimally invasive total hysterectomy and bilateral salpingo-oophorectomy with sentinel lymph node mapping (FIRES, SENTOR); omentectomy for serous histology.
- How do the results of FIRES & SENTOR (sentinel node mapping) apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Fertility-sparing (grade 1, stage IA, no invasion)
- For my situation (fertility-sparing (grade 1, stage ia, no invasion)), which of the standard options do you recommend and why?Guideline options include: Progestin (oral or IUD) with re-biopsy every 3-6 months; hysterectomy after childbearing.
- Am I a candidate for Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD), and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Adjuvant, low and intermediate risk
- For my situation (adjuvant, low and intermediate risk), which of the standard options do you recommend and why?Guideline options include: Observation (low risk, POLEmut) or vaginal brachytherapy (intermediate risk; PORTEC-2); molecular class may de-escalate (PORTEC-4a).
Adjuvant, high risk (stage III, serous, p53abn, deep invasion grade 3)
- For my situation (adjuvant, high risk (stage iii, serous, p53abn, deep invasion grade 3)), which of the standard options do you recommend and why?Guideline options include: Chemoradiation plus carboplatin-paclitaxel (PORTEC-3) or chemotherapy alone (GOG-258); pembrolizumab or dostarlimab added for stage III-IV per RUBY/GY018 eligibility.
- Am I a candidate for Carboplatin, Paclitaxel / nab-paclitaxel, Pembrolizumab or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of PORTEC-3 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Advanced or recurrent, first line (any MMR status)
- For my situation (advanced or recurrent, first line (any mmr status)), which of the standard options do you recommend and why?Guideline options include: Carboplatin-paclitaxel plus dostarlimab (RUBY), pembrolizumab (NRG-GY018/KEYNOTE-868), or durvalumab (DUO-E; dMMR in the US), continued as maintenance up to 2-3 years.
- Am I a candidate for Dostarlimab, Pembrolizumab, Durvalumab, and what side effects should I expect?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?Trial populations differ from individual patients; ask how closely you match.
Recurrent, pMMR, after platinum
- For my situation (recurrent, pmmr, after platinum), which of the standard options do you recommend and why?Guideline options include: Lenvatinib + pembrolizumab (KEYNOTE-775) if not previously given immunotherapy; T-DXd if HER2 IHC 3+; chemotherapy (doxorubicin, weekly paclitaxel); hormonal therapy for low-grade ER-positive disease.
- Am I a candidate for Lenvatinib, Pembrolizumab, Trastuzumab deruxtecan or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of KEYNOTE-775 / Study 309 and DESTINY-PanTumor02 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Recurrent, dMMR, after chemotherapy
- For my situation (recurrent, dmmr, after chemotherapy), which of the standard options do you recommend and why?Guideline options include: Single-agent PD-1 blockade (dostarlimab GARNET, pembrolizumab) if immunotherapy-naive; otherwise chemotherapy or trials.
- Am I a candidate for Dostarlimab, Pembrolizumab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
HER2-positive serous
- For my situation (her2-positive serous), which of the standard options do you recommend and why?Guideline options include: Trastuzumab with carboplatin-paclitaxel (randomised phase 2) or T-DXd for IHC 3+ after prior therapy.
- Am I a candidate for Trastuzumab, Trastuzumab deruxtecan, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of DESTINY-PanTumor02 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of Sacituzumab tirumotecan, Puxitatug samrotecan, Saruparib, HS-20089?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?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?Supportive care improves quality of life and helps patients complete treatment.
- I read that “p53-abnormal disease behaves like serous ovarian”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Obesity-driven incidence rising”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- A Clinical Study of the Anti-cancer Effects of an Investigational Therapy or Chemotherapy in Patients With Recurring Uterine CancerPhase 3 · recruiting · NCT06340568A Phase III, Randomized, Multi-site, Open-label Trial of BNT323/DB-1303 Versus Investigator's Choice of Chemotherapy in Previously Treated Patients With HER2- Expressing Recurrent Endometrial Cancer
- A Phase 3B Study to Evaluate Bone Mineral Density With Long-Term Use of Relugolix Combination Tablet in Women With Uterine Fibroids or EndometriosisPhase 3 · recruiting · NCT05862272A Phase 3B, Single-Arm, Open-Label Study to Evaluate Bone Mineral Density With Long-Term Use of Relugolix Combination Tablet in Premenopausal Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids or Moderate to Severe Pain Associated With Endometriosis
- A Study to Compare Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) Versus Pembrolizumab Alone as Treatment in ParticipanPhase 3 · recruiting · NCT06952504A Phase 3 Randomized, Open-label, Multicenter Study to Compare the Efficacy and Safety of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) in Combination With Pembrolizumab Versus Pembrolizumab Alone as First-line Maintenance Treatment in Participants With Mismatch Repair Proficient Endometrial Cancer (TroFuse-033/GOG-3119/ENGOT-en29)
- A Study to Evaluate the Use of Durvalumab in Combination With Platinum-based Chemotherapy Followed by Durvalumab With Olaparib as First-line TreatmentPhase 3 · active · NCT06746116A Phase IIIB Study to Evaluate the Use of Durvalumab in Combination With Platinum-based Chemotherapy Followed by Durvalumab With Olaparib as First-line Treatment in Patients With Newly Diagnosed pMMR Advanced or Recurrent Endometrial Cancer in Spain
- A Study to Investigate Mocertatug Rezetecan Compared With Chemotherapy in Participants With Endometrial Cancer After Platinum-based Chemotherapy and Immunotherapy (BEHOLD-Endometrial01)Phase 3 · recruiting · NCT07286331A Randomized, Open-label, Multicenter, Phase 3 Study to Investigate Mocertatug Rezetecan Compared With Chemotherapy in Participants With Endometrial Cancer After Platinum-based Chemotherapy and Immunotherapy
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Endometrial cancer: the full pageThe gynaecological cancer where immunotherapy has had the biggest impact, guided by molecular classification.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Guidelines comparedNCCN, ESMO and NICE side by side for this cancer.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- Endometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP): Four groups defined by a few tests that predict outcome better than the microscope: POLE-mutated (excellent), mismatch-repair deficient, p53-abnormal (worst), and 'no specific profile'.
- Glycaemic index and glycaemic load: How fast a food raises blood sugar (index) and how much, given the portion (load).
- Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR): The 'normal' result on the mismatch-repair test: the tumour has intact DNA spell-checking and few mutations.
- Lynch syndrome: Lynch syndrome is the most common inherited cancer syndrome: a faulty mismatch-repair gene raises lifetime bowel cancer risk to 40-80% and also endometrial and other cancers.
- Hysterectomy: Removing the uterus (womb), often with the cervix, tubes and ovaries.
- Metabolic syndrome and insulin resistance: Metabolic syndrome is a cluster of central obesity, high blood pressure, high blood sugar and abnormal blood fats.
- TP53-mutated (p53-abnormal): Loss of the p53 'guardian of the genome', the most commonly mutated gene in cancer.
- Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR): Microsatellite instability is the mark of a broken DNA spell-checker (loss of MLH1, MSH2, MSH6 or PMS2) that leaves thousands of mutations, so the tumour displays abnormal proteins that T cells can recognise.
- Tumour-agnostic (tissue-agnostic) approval: A tumour-agnostic approval lets a drug be used for any cancer carrying a specific molecular feature, regardless of where it started.
- Obesity-related cancers (IARC list of 13): Excess body fat is an established cause of thirteen cancers on the IARC list, including womb, oesophagus, kidney, liver, bowel, pancreas and postmenopausal breast cancer.
Every term links to the glossary.