The first 60 days: Endometrial cancer with no specific molecular profile
Endometrial cancer with no specific molecular profile is the default class: no POLE mutation, intact mismatch repair and normal p53. Most are low-grade, oestrogen-driven tumours cured by hysterectomy, and hormone-blocking drugs are their most natural treatment when they do recur. Below, week by week, is what OnCo's record of Endometrial cancer with no specific molecular profile 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.
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.
- SurgeonNamed in the standard of care for: Low risk (stage IA grade 1 to 2, no substantial LVSI), Fertility-sparing (grade 1, stage IA, no invasion).
- Medical oncologistNamed in the standard of care for: Intermediate and high-intermediate risk, Fertility-sparing (grade 1, stage IA, no invasion), Advanced or recurrent, first line, After platinum.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Intermediate and high-intermediate risk.
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.
Hysterectomy with bilateral salpingo-oophorectomy and sentinel node mapping; no adjuvant treatment.
Vaginal brachytherapy (PORTEC-2) or pelvic radiotherapy; chemotherapy adds little in this class.
Levonorgestrel intrauterine device or oral progestin with hysteroscopic sampling every three to six months; hysterectomy after childbearing.
Carboplatin-paclitaxel with pembrolizumab or dostarlimab (smaller benefit than in dMMR); endocrine therapy for low-grade receptor-positive disease.
Lenvatinib with pembrolizumab (KEYNOTE-775); aromatase inhibitor with or without a CDK4/6 inhibitor in receptor-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 Negative POLE, MMR and p53 results, Oestrogen and progesterone receptor expression, L1CAM expression, CTNNB1 exon 3 mutation, Grade, depth of invasion and lymphovascular space invasion), 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 Low-grade endometrioid, oestrogen receptor-positive NSMP, CTNNB1-mutant low-grade NSMP, L1CAM-positive or oestrogen receptor-negative NSMP.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Low risk (stage IA grade 1 to 2, no substantial LVSI)
- For my situation (low risk (stage ia grade 1 to 2, no substantial lvsi)), which of the standard options do you recommend and why?Guideline options include: Hysterectomy with bilateral salpingo-oophorectomy and sentinel node mapping; no adjuvant treatment.
- 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.
Intermediate and high-intermediate risk
- For my situation (intermediate and high-intermediate risk), which of the standard options do you recommend and why?Guideline options include: Vaginal brachytherapy (PORTEC-2) or pelvic radiotherapy; chemotherapy adds little in this class.
- How do the results of PORTEC-3 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: Levonorgestrel intrauterine device or oral progestin with hysteroscopic sampling every three to six 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.
Advanced or recurrent, first line
- For my situation (advanced or recurrent, first line), which of the standard options do you recommend and why?Guideline options include: Carboplatin-paclitaxel with pembrolizumab or dostarlimab (smaller benefit than in dMMR); endocrine therapy for low-grade receptor-positive disease.
- 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 NRG-GY018 / KEYNOTE-868 and RUBY / ENGOT-EN6 / GOG-3031 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
After platinum
- For my situation (after platinum), which of the standard options do you recommend and why?Guideline options include: Lenvatinib with pembrolizumab (KEYNOTE-775); aromatase inhibitor with or without a CDK4/6 inhibitor in receptor-positive disease.
- Am I a candidate for Lenvatinib, Pembrolizumab, Letrozole (and other aromatase inhibitors) 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 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 Abemaciclib, Letrozole (and other aromatase inhibitors), Molecular-class-directed adjuvant therapy in endometrial cancer, XPORT-EC-042 / ENGOT-EN20 / GOG-3083?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 “Splitting the class into truly low-risk and higher-risk tumours with L1CAM, CTNNB1 and receptor status”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Whether progestins can replace chemotherapy after surgery”. How does that affect my plan?Open problems are where trials and second opinions matter most.
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 with no specific molecular profile: the full pageEndometrial cancer with no specific molecular profile is the default class: no POLE mutation, intact mismatch repair and normal p53. Most are low-grade, oestrogen-driven tumours cured by hysterectomy, and hormone-blocking drugs are their most natural treatment when they do recur.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- 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.
- 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'.
- Hysterectomy: Removing the uterus (womb), often with the cervix, tubes and ovaries.
Every term links to the glossary.