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Endometrial cancer with no specific molecular profile: the decisions you may face

5 treatment settings, 5 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.

Early / localised

Low risk (stage IA grade 1 to 2, no substantial LVSI)

2 options

Hysterectomy with bilateral salpingo-oophorectomy and sentinel node mapping; no adjuvant treatment.

The options, in plain words

Removing just the first lymph node a tumour drains to, instead of all of them, to check for spread.

  • Avoids lymphoedema from full dissection

Surgeons operate through small incisions using robotic arms with tremor-free precision and 3D vision.

  • Precision, shorter stay
  • Enables complex minimally invasive resections
The evidence behind it
The main trade-offs on record
  • False negatives in ~5-10%
  • Cost
  • Loss of haptic feedback
  • Not superior for every indication
Questions to ask about this decision
  1. Between Sentinel lymph node biopsy and Robotic & minimally invasive surgery, 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.
  2. 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.
  3. How closely do I match the people in FIRES & SENTOR (sentinel node mapping), 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.
  4. 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.
  5. For my situation (low risk (stage ia grade 1 to 2, no substantial lvsi)), which of the standard options do you recommend and why?
    Why: Guideline options include: Hysterectomy with bilateral salpingo-oophorectomy and sentinel node mapping; no adjuvant treatment.
  6. How do the results of FIRES & SENTOR (sentinel node mapping) 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.

Early / localised

Intermediate and high-intermediate risk

2 options

Vaginal brachytherapy (PORTEC-2) or pelvic radiotherapy; chemotherapy adds little in this class.

The options, in plain words
BrachytherapyStandard of care

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
The evidence behind it
  • 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
The main trade-offs on record
  • Invasive
  • Declining expertise in some regions
  • Low-dose bath to normal tissue
  • Motion management
Questions to ask about this decision
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. For my situation (intermediate and high-intermediate risk), which of the standard options do you recommend and why?
    Why: Guideline options include: Vaginal brachytherapy (PORTEC-2) or pelvic radiotherapy; chemotherapy adds little in this class.
  6. 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.

Special situations

Fertility-sparing (grade 1, stage IA, no invasion)

2 options

Levonorgestrel intrauterine device or oral progestin with hysteroscopic sampling every three to six months; hysterectomy after childbearing.

The options, in plain words

For young women with the earliest, low-grade endometrial cancers, progestin pills or a hormonal IUD can clear the cancer and allow pregnancy before a later hysterectomy.

  • Preserves fertility in a disease increasingly diagnosed in women under 45
  • Minimal toxicity

Progesterone-like hormones that can reverse early endometrial cancer in women who want to keep their uterus, and control advanced hormone-sensitive disease.

The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
  • Recurrence risk ~30%
  • Requires strict imaging and biopsy follow-up
  • Not appropriate for grade 2-3, p53-abnormal, or invasive disease
Questions to ask about this decision
  1. Between Fertility-sparing hormonal treatment of early endometrial cancer and Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD), 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.
  2. 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.
  3. 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.
  4. For my situation (fertility-sparing (grade 1, stage ia, no invasion)), which of the standard options do you recommend and why?
    Why: Guideline options include: Levonorgestrel intrauterine device or oral progestin with hysteroscopic sampling every three to six months; hysterectomy after childbearing.
  5. Am I a candidate for Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD), 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.

Second line

Advanced or recurrent, first line

Carboplatin-paclitaxel with pembrolizumab or dostarlimab (smaller benefit than in dMMR); endocrine therapy for low-grade receptor-positive disease.

The options, in plain words

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.

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.

Dostarlimab is a PD-1 blocker famous for making rectal cancer disappear without surgery in every patient with a mismatch-repair-deficient tumour.

Daily pills that stop the body making oestrogen after menopause, the backbone of hormone therapy for most breast cancers.

Progesterone-like hormones that can reverse early endometrial cancer in women who want to keep their uterus, and control advanced hormone-sensitive disease.

The evidence behind it
The main trade-offs on record
  • Dose by Calvert formula using GFR (see the calculators).
Side effectAny gradeGrade 3+
Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients8%-
Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients3.4%-
Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients1.7%-
Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients0.7%-
  • 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.

Questions to ask about this decision
  1. Between Carboplatin, Paclitaxel / nab-paclitaxel, Pembrolizumab 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.
  2. 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.
  3. How closely do I match the people in NRG-GY018 / KEYNOTE-868 and RUBY / ENGOT-EN6 / GOG-3031, 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.
  4. 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.
  5. 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.
  6. 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 pembrolizumab or dostarlimab (smaller benefit than in dMMR); endocrine therapy for low-grade receptor-positive disease.
  7. Am I a candidate for Carboplatin, Paclitaxel / nab-paclitaxel, Pembrolizumab or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  8. How do the results of NRG-GY018 / KEYNOTE-868 and RUBY / ENGOT-EN6 / GOG-3031 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.

Lenvatinib with pembrolizumab (KEYNOTE-775); aromatase inhibitor with or without a CDK4/6 inhibitor in receptor-positive disease.

The options, in plain words

An oral anti-angiogenic pill that matched sorafenib in liver cancer with higher response rates, and partners with pembrolizumab in kidney and endometrial cancer.

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.

Daily pills that stop the body making oestrogen after menopause, the backbone of hormone therapy for most breast cancers.

Abemaciclib was the first CDK4/6 inhibitor approved after surgery for high-risk hormone-positive breast cancer.

The evidence behind it
The main trade-offs on record
  • Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
  • Reduce to 14 mg (thyroid) or 10 mg (RCC) in severe impairment.
  • Reduce in severe renal impairment.
Side effectAny gradeGrade 3+
Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients8%-
Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients3.4%-
Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients1.7%-
Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients0.7%-
  • 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 effectAny gradeGrade 3+
Neutropenia · 37-46% any grade; 19-32% grade 3-442%19%
Diarrhoea · 81-90% any grade; 8-20% grade 3 across trials85%8%
Infections · monarchE / MONARCH 2-3%
Venous thromboembolism · 2-5% across trials-2%
  • Avoid grapefruit. Diarrhoea: start loperamide at the first loose stool.
  • Reduce to once daily in severe impairment.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Questions to ask about this decision
  1. Between Lenvatinib, Pembrolizumab, Letrozole (and other aromatase inhibitors) 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.
  2. 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.
  3. How closely do I match the people in KEYNOTE-775 / Study 309, 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.
  4. Which side effects of Pembrolizumab or Abemaciclib 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.
  5. 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.
  6. For my situation (after platinum), which of the standard options do you recommend and why?
    Why: Guideline options include: Lenvatinib with pembrolizumab (KEYNOTE-775); aromatase inhibitor with or without a CDK4/6 inhibitor in receptor-positive disease.
  7. Am I a candidate for Lenvatinib, Pembrolizumab, Letrozole (and other aromatase inhibitors) or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  8. How do the results of KEYNOTE-775 / Study 309 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.

How to read this page. Options and results come from OnCo records with their sources; the settings are the standard-of-care rows on the cancer page, and the lines of therapy are on the sequencing grid. Where a setting names one path, the choice is usually about timing, trials and where to be treated: see expert centres. OnCo is orientation, not medical advice.