Latest Cancer TreatmentsDr. Mohammadreza Dabiri
Dr. Mohammadreza Dabiriفارسی
Cancer type

Endometrial (womb) cancer

Take bleeding after the menopause seriously: most womb cancers are found early and are cured by surgery

Updated: 28 October 202616 min read45 references
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Key points

  • Endometrial cancer (cancer of the womb) starts in the inner lining of the womb and is different from cervical cancer [3]. In high-income countries it is the most common cancer of the female reproductive organs, and the main reason it is becoming more common is obesity [1].
  • The most important sign is bleeding after the menopause: about 9 in 10 patients have it. But fewer than 1 in 10 women who bleed after the menopause have cancer [5].
  • There is no screening test for women at average risk, and a smear test (Pap test) does not find womb cancer; the best thing to do is to see a doctor promptly about any unusual bleeding [7].
  • Because this cancer usually causes symptoms early, most patients are diagnosed early and are cured by surgery to remove the womb [1, 9].
  • Today the tumour's "genetic type" (four molecular groups) is also tested; it helps each patient get exactly the treatment she needs: no less, no more [2, 11].
  • In advanced or recurrent disease, adding immunotherapy to chemotherapy has delayed the growth of the cancer and, in one large study, also helped patients live longer; the benefit is largest in tumours with a DNA repair defect (dMMR) [26, 28, 29].

What is endometrial (womb) cancer?

The womb (uterus) is a hollow, muscular organ in the pelvis where a baby grows. Its inner lining is called the endometrium, and endometrial cancer starts in the cells of this lining [3]. The lower, narrow end of the womb is the cervix, which opens into the vagina; cervical cancer is a different disease [3]. Cancer that starts in the muscle of the womb wall (uterine sarcoma) is also separate and is treated differently [3].

Endometrial cancer is the most common cancer of the female reproductive organs in high-income countries, and it is becoming more common worldwide; an ageing population and, above all, obesity are the main reasons [1]. In 2020 about 417,000 women worldwide were diagnosed with it and about 97,000 died of it [2].

The good news is that this cancer usually shows itself early through bleeding, so most patients are diagnosed early and are cured by surgery [1, 9].

For patients

The pathologist writes the tumour type in the report. Endometrial cancers fall into two broad groups [11]:

  • Less aggressive types (endometrioid, grade 1 or 2): if they are still inside the womb, the outlook is good [11].
  • Aggressive types (grade 3 endometrioid, serous, clear cell, carcinosarcoma and a few rare types): they need more complete treatment [11].

Signs and symptoms

The most common and most important symptom is bleeding after the menopause, meaning any bleeding from the womb that happens one year or more after the last period [8]. About 9 in 10 women with womb cancer have this symptom [5]. Even a single episode of bleeding or spotting needs to be checked [8].

Other symptoms [4]:

  • Vaginal bleeding or discharge not related to periods (for example, between periods)
  • Pain or difficulty passing urine
  • Pain during sex
  • Pain in the pelvis

Most women who bleed after the menopause do not have cancer: fewer than 1 in 10 do [5]. But because almost all patients have this symptom, checking this bleeding is the best way to find the cancer early [5]. Read more: Symptoms of womb cancer

When should I see a doctor?

If you have any of these, see a doctor (ideally a gynaecologist) promptly:

  • Any bleeding or spotting after the menopause, even once and even if it is light [8, 4]
  • Unusual bleeding or discharge not related to your periods [4]
  • Any vaginal bleeding while you are taking tamoxifen [7]
  • Bleeding that continues or comes back after a first check [8]
  • Pelvic pain, pain during sex or pain on passing urine that does not go away [4]

Most of these bleeds have a harmless cause [5], but the check is simple and finding cancer early makes treatment simpler.

Risk factors, Lynch syndrome and screening

Most risk factors come down to the endometrium being exposed to the hormone oestrogen for many years [6]. The main ones [6, 10]:

  • Obesity and weight gain in adult life; the main reason this cancer is increasing worldwide [1, 6]
  • Type 2 diabetes and "metabolic syndrome" (extra fat around the waist, high blood sugar, high blood pressure and high blood fats) [6]
  • Oestrogen-only hormone therapy after the menopause; the longer it is used, the higher the risk. Oestrogen combined with a progestogen does not raise the risk of womb cancer, but it does raise the risk of breast cancer [6].
  • Tamoxifen (a breast cancer medicine) taken for more than 2 years, especially after the menopause [6]. Do not stop it on your own; just tell your doctor promptly about any bleeding [7].
  • Polycystic ovary syndrome [6]
  • Lynch syndrome (an inherited condition), and womb cancer in a mother, sister or daughter [6]
  • Early first period, late menopause and never having been pregnant [6]
  • Abnormal thickening of the womb lining (hyperplasia) [6]

On the other hand, pregnancy and breastfeeding, the combined contraceptive pill, physical activity and weight-loss (bariatric) surgery lower the risk [6].

Is there a screening test for womb cancer?

For women at average risk, no. No regular test has been shown to reduce deaths from womb cancer [7]. The smear test (Pap test) is for cervical cancer and is not used to find womb cancer [7]. Regular ultrasound scans in women without symptoms, even women taking tamoxifen, are not useful; in these women a scan is needed only if they have bleeding [7].

This cancer usually causes bleeding and is found early [7], so the best "screening" is to take any unusual bleeding seriously.

Lynch syndrome: special check-ups

Lynch syndrome is an inherited condition that greatly increases the risk of womb cancer [6] and is also linked to bowel and ovarian cancer [7, 2]. The European guideline recommends for these women [2]:

  • from about age 30, a vaginal ultrasound every year and a sample of the womb lining every 1 or 2 years, until the womb is removed;
  • once they have finished having children, removal of the womb, tubes and ovaries by keyhole surgery; for most types of the syndrome preferably before age 40, and for one type (PMS2) around the menopause;
  • if the ovaries are removed before the menopause, hormone replacement is offered.

Also, the tumour of every woman with womb cancer should be tested for MMR, so that if Lynch syndrome is possible, genetic counselling and testing can be offered to her and her family [2]. Read more: Is cancer hereditary?

Diagnosis and staging

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How womb cancer is diagnosed

  1. 1

    Ultrasound and a tissue sample at the first visit

    For most women who bleed after the menopause, a vaginal ultrasound (to measure the thickness of the womb lining) and a sample of the womb lining are recommended together [8]. Ultrasound alone is enough only for a small group: a single episode of bleeding, a thin and fully seen womb lining, no major risk factors, and quick access to follow-up [8].

  2. 2

    Endometrial biopsy

    The doctor passes a thin, flexible tube through the cervix and takes a little of the womb lining to be examined under a microscope [9].

  3. 3

    Hysteroscopy or D&C

    Sometimes the doctor looks inside the womb with a thin camera (hysteroscopy) and takes a sample from the suspicious area, or takes a larger sample by dilatation and curettage (D&C) [9].

  4. 4

    Genetic tests on the sample

    The same sample is tested for MMR, p53, POLE and the oestrogen receptor [2]. The results help choose treatment and show whether genetic counselling for Lynch syndrome is needed [2].

  5. 5

    Imaging

    Usually an examination, a vaginal ultrasound, a pelvic MRI to see how deeply the tumour has grown into the womb wall, and blood tests [10]. In high-risk patients, a CT or PET scan to look for spread in the body [10].

  6. 6

    Staging at surgery

    The final stage is set after surgery, once the womb, tubes, ovaries and sentinel lymph nodes have been examined [2, 11].

For patients
Stages of womb cancer in plain words
StageWhat it means
1The cancer is only in the body of the womb [11]
2It is still in the womb but has reached the tissue of the cervix, or is seen in many small vessels, or is an aggressive type that has grown into the womb wall [11]
3It has spread outside the womb: to an ovary or tube, the outer surface of the womb, the vagina, the tissues beside the womb, the lining of the pelvis or the lymph nodes [11]
4It has reached the inner lining of the bladder or bowel, or has spread into the abdomen beyond the pelvis or to distant parts of the body [11]

In the new staging system, the result of the tumour's genetic tests can also move the stage down or up [11].

For physiciansFIGO 2023 staging of endometrial cancer
For physicians
FIGO 2023 staging of endometrial cancer
StageDefinition
IA1Non-aggressive histological type limited to a polyp or confined to the endometrium [11]
IA2Non-aggressive type with invasion of less than 50% of the myometrium and no or focal LVSI [11]
IA3Low-grade endometrioid carcinoma limited to the uterus with simultaneous low-grade endometrioid ovarian involvement (myoinvasion less than 50%, no substantial LVSI, no other metastases, unilateral ovarian tumour limited to the ovary without capsule rupture) [11]
IBNon-aggressive type with invasion of 50% or more of the myometrium and no or focal LVSI [11]
ICAggressive type without any myometrial invasion (limited to a polyp or the endometrium) [11]
IIAInvasion of the cervical stroma by a non-aggressive type [11]
IIBSubstantial LVSI in a non-aggressive type [11]
IICAggressive type with any myometrial invasion [11]
IIIA1Spread to the ovary or fallopian tube (except cases meeting stage IA3 criteria) [11, 2]
IIIA2Involvement of the uterine subserosa or spread through the uterine serosa [11, 2]
IIIB1Metastasis or direct spread to the vagina and/or parametria [11, 2]
IIIB2Metastasis to the pelvic peritoneum [11, 2]
IIIC1Pelvic lymph node metastasis: IIIC1i micrometastasis, IIIC1ii macrometastasis [11, 2]
IIIC2Para-aortic lymph node metastasis up to the renal vessels: IIIC2i micrometastasis, IIIC2ii macrometastasis [11, 2]
IVAInvasion of the bladder and/or intestinal mucosa [11, 2]
IVBPeritoneal metastasis beyond the pelvis [11, 2]
IVCDistant metastasis [11, 2]
IAm POLEmutStage I and II disease with a pathogenic POLE mutation [2, 11]
IICm p53abnStage I and II disease with abnormal p53 and myometrial invasion [2, 11]

Aggressive types: grade 3 endometrioid, serous, clear cell, undifferentiated, mixed, mesonephric-like, gastrointestinal-type mucinous carcinoma and carcinosarcoma; non-aggressive types: grade 1 and 2 endometrioid [11]. Micrometastasis: deposits larger than 0.2 mm and up to 2 mm, or more than 200 cells; the significance of isolated tumour cells (0.2 mm or less) is unclear [IV, C] [2]. When the molecular classification is known, the stage is reported with "m" and the molecular subtype [11].

Molecular classification: four genetic groups of tumour

For patients

Today, as well as the stage, the tumour's "genetic type" is also tested. Endometrial cancers fall into four groups [12, 2]:

  • POLE mutation: even if it looks aggressive under the microscope, the outlook is excellent; in one large study almost none of these patients had their cancer come back [13]. Often no further treatment is needed after surgery [2].
  • DNA repair defect (dMMR): responds very well to immunotherapy [26, 28] and is sometimes a sign of Lynch syndrome [2].
  • Abnormal p53: the most aggressive group; stronger treatment (chemotherapy with radiotherapy) helps these patients most [13].
  • No specific molecular profile: the risk depends mostly on the tumour grade and the oestrogen receptor [2].

Ask your doctor what these test results show in your report; they may make your treatment lighter or more complete [2].

For physiciansMolecular groups, prognosis (in the high-risk PORTEC-3 population) and treatment implications
For physicians
Molecular groups, prognosis (in the high-risk PORTEC-3 population) and treatment implications
GroupHow it is identifiedPrognosis in PORTEC-3Treatment implications (ESGO/ESTRO/ESP 2025)
POLEmutSequencing of all 11 pathogenic POLE exonuclease domain variants [IV, B] [2]12% of patients; 5-year recurrence-free survival 98% (100% with chemoradiotherapy vs 97% with radiotherapy) [13]Stages I and II → IAm POLEmut and low risk, no adjuvant therapy; in IIIm and IVAm data are insufficient and de-escalation after multidisciplinary discussion can be considered [IV, B] [2]
MMRdIHC for MMR proteins (two-‎ and four-antibody approaches are equivalent); MLH1 promoter methylation testing when MLH1 is lost; MSI by PCR if results are equivocal [IV, B] [2]33%; 5-year recurrence-free survival 72%; no benefit from adding chemotherapy (68% vs 76%) [13]Advanced or recurrent disease: immune checkpoint inhibitor + carboplatin–paclitaxel, then maintenance [I, A]; after surgery in IIIm and IVAm: chemotherapy + immune checkpoint inhibitor should be considered [II, B] [2]
p53abnp53 IHC (overexpression, null or cytoplasmic pattern); TP53 sequencing if the pattern is equivocal or heterogeneous [IV, B] [2]23%; 5-year recurrence-free survival 48%; 59% with chemoradiotherapy vs 36% with radiotherapy (P=0.019) [13]Stages I and II with myometrial invasion → IICm p53abn and high risk: external beam radiotherapy with concurrent and adjuvant chemotherapy [I, A] [2]
NSMPNone of the three features above; oestrogen receptor by IHC (positive: 10% or more) [IV, A] [2]32%; 5-year recurrence-free survival 74% (80% vs 68%; P=0.243) [13]Low-grade ER-positive NSMP versus high-grade or ER-negative NSMP determines the risk group [2]

Multiple classifiers: POLEmut with MMRd or p53abn → POLEmut; MMRd with p53abn → MMRd [IV, B]. Testing on the biopsy or curettage specimen is preferred and is repeated on the hysterectomy specimen only in specific situations [IV, B]. In advanced or recurrent p53abn cancer and in all serous carcinomas and carcinosarcomas, HER2 overexpression can be assessed by IHC [IV, C] [2].

Treatment by stage

The main treatments

Surgery

The main treatment: removal of the whole womb and cervix together with both tubes and ovaries, and checking of the sentinel lymph nodes [2]. Most patients have keyhole surgery (laparoscopic or robotic), which has fewer complications and a shorter hospital stay and works as well as open surgery [2, 14, 16].

Radiotherapy

After surgery, to lower the chance of the cancer coming back in the vagina or pelvis: internal radiotherapy to the vagina (brachytherapy) or external radiotherapy to the pelvis, depending on the risk [2, 19]. If surgery is not possible, radiotherapy can be the main treatment [2].

Chemotherapy

For high-risk or spread disease; usually two drugs, carboplatin and paclitaxel, every 3 weeks; in advanced disease usually 6 cycles [10, 2].

Immunotherapy

Medicines that switch the immune system on against the cancer; given with chemotherapy in advanced or recurrent disease, especially in dMMR tumours [2, 26, 28].

Hormone therapy

Progestogen tablets or anti-oestrogen medicines; for less aggressive, slow-growing tumours with hormone receptors [2], and for young women who want to keep the womb for a while [33].

For patients

Treatment at each stage, in plain words

  1. 1

    Stage 1, low risk

    Surgery alone; usually no other treatment is needed [2].

  2. 2

    Stage 1 or 2, intermediate risk

    Surgery, and often internal radiotherapy to the vagina (brachytherapy), which in the main study was 3 short sessions one week apart [2, 20]; sometimes external radiotherapy to the pelvis [2]. Some younger patients, or those with a low-grade tumour, can skip radiotherapy [2].

  3. 3

    Stage 1 or 2 high risk, and stage 3

    Surgery, followed by chemotherapy with radiotherapy, or chemotherapy alone [2, 22, 23]. In stage 3 dMMR tumours, adding immunotherapy may also be considered [2].

  4. 4

    Stage 4 or cancer that has come back

    Chemotherapy with immunotherapy [2, 26, 28]; for less aggressive, slow-growing tumours with hormone receptors, hormone tablets [2]. If the cancer comes back after chemotherapy, immunotherapy alone or with the tablet lenvatinib [2, 32]. Sometimes surgery or radiotherapy is also used for limited disease [2].

  5. 5

    If surgery is not possible

    External radiotherapy and radiotherapy inside the womb instead of surgery [2].

For physiciansAdjuvant treatment by risk group (ESGO/ESTRO/ESP 2025)
For physicians

Adjuvant treatment by risk group (ESGO/ESTRO/ESP 2025)

  1. 1

    Low risk

    IAm (IA1, IA2, IA3) POLEmut, MMRd or low-grade ER-positive NSMP; IBm POLEmut; ICm POLEmut or MMRd; IIm POLEmut. No adjuvant therapy is recommended [II, A] [2].

  2. 2

    Intermediate risk

    IBm MMRd or low-grade ER-positive NSMP; IIAm low-grade ER-positive NSMP; IICm MMRd with myometrial invasion, without cervical stromal invasion and without substantial LVSI. Adjuvant vaginal brachytherapy should be considered [I, A]; no adjuvant therapy is also an option [III, C], especially under 60 years or for low-grade tumours [II, A] [2].

  3. 3

    High–intermediate risk

    IIAm MMRd; IIBm MMRd or low-grade ER-positive NSMP; IICm MMRd with cervical invasion or substantial LVSI. External beam radiotherapy for optimal pelvic control [II, A]; vaginal brachytherapy is an alternative, especially after nodal staging with pN0 [II, B]; no adjuvant therapy can be considered in pN0 without substantial LVSI and low grade [IV, B] [2].

  4. 4

    High risk

    IA2m, IA3m, IBm and IIm in high-grade or ER-negative NSMP or p53abn; IIIm and IVAm in MMRd, NSMP and p53abn. External beam radiotherapy with concurrent and adjuvant chemotherapy [I, A] or sequential chemotherapy and radiotherapy [I, B]; chemotherapy with or without brachytherapy is an alternative [I, B]; in IIIm and IVAm MMRd, chemotherapy plus an immune checkpoint inhibitor (with or without external beam radiotherapy) should be considered [II, B] [2].

  5. 5

    Uncertain risk

    IA1m and ICm in high-grade or ER-negative NSMP or p53abn: scarce data; adjuvant therapy is generally not recommended [IV, C]. IIIm and IVAm POLEmut: after multidisciplinary discussion, de-escalation from high-risk treatment can be considered [IV, B] [2].

  6. 6

    Medically unfit for surgery

    Definitive radiotherapy: EBRT plus image-guided intrauterine brachytherapy for high-grade tumours or deep myometrial invasion; for low-grade tumours without deep invasion, brachytherapy alone is an alternative [II, B]. Vaginal hysterectomy with bilateral salpingo-oophorectomy if feasible [IV, C] [2].

Keeping the womb for pregnancy in young women

For patients

In young women who still want to become pregnant, the womb can be kept for a while in one specific group: grade 1 endometrioid cancer that is only in the womb lining and has not grown into the womb wall [33]. This decision should be made at a specialist centre, together with a gynaecological cancer specialist and a fertility specialist [33].

The best approach is removal of the lesion by hysteroscopy followed by progestogen tablets or a hormone-releasing coil (IUD) [33]. Treatment usually lasts 6 to 12 months and is checked with regular biopsies [33]. Losing weight improves the chances of the treatment working and of pregnancy [33]. Once you have finished having children, removal of the womb is recommended [33]. Read more: Sex and fertility

For physiciansESGO/ESHRE/ESGE guideline
For physicians

ESGO/ESHRE/ESGE guideline: fertility-sparing treatment for grade 1 endometrioid carcinoma, stage IA without myometrial invasion and without risk factors [V, A]; for grade 2, case by case [IV, C]. Hysteroscopic-guided biopsy is preferred over blind biopsy [III, A]; myometrial invasion should be assessed by MRI or transvaginal ultrasound by a specialised radiologist or sonographer [III, A], CT should not be used for this [III, A], and MRI or CT for nodes and metastases [II, B]. Hysteroscopic resection followed by oral progestogens and/or an LNG-IUD gives the highest complete response and live birth rates [II, B]; GnRH analogues are not first line [II, B] [33].

Complete response should be reached within 6 to 12 months [III, B], with a maximum of 15 months [IV, C]; no response at all at 6 months → multidisciplinary counselling [IV, B]. Success: two consecutive biopsies showing complete response at least 3 months apart [IV, C]; follow-up with examination and ultrasound every 3 months and histological assessment by hysteroscopy every 3 to 6 months [IV, B]. Conservative treatment is inappropriate for p53abn tumours [IV, D]; MMR IHC is mandatory to identify Lynch syndrome [III, A], and in Lynch syndrome the decision is case by case [II, A]. Definitive surgery for non-response, inability to conceive, recurrence or progression [II, A], and completion surgery after childbearing [II, A]; removal of the ovaries case by case [III, B] [33]. Doses are given in the section "Treatment regimens and doses (for doctors)".

If the cancer is advanced or comes back

For patients

If the cancer has spread beyond the pelvis or has come back after treatment, chemotherapy and immunotherapy are usually given together, and then immunotherapy continues on its own [2]. In large studies this combination delayed the growth of the cancer [26, 28], and in one of them it also helped patients live longer [29]. The benefit was largest in dMMR tumours: one year after starting treatment, about twice as many patients were free of cancer growth [26].

For less aggressive, slow-growing tumours with hormone receptors, hormone tablets (progestogens) can be the first treatment [2]. If the cancer comes back after chemotherapy, immunotherapy alone (in dMMR tumours) or with the tablet lenvatinib are the next options [2, 32]. If only one or a few limited spots are affected, surgery or radiotherapy may also be possible [2]. Read about the side effects of immunotherapy: Immunotherapy side effects

What should I do after the diagnosis?

What should I do after a womb cancer diagnosis?1 / 7
1

Most womb cancers can be cured

Because this cancer is usually found early, most patients are cured by surgery [1, 9]. You do not have to make every decision in one day.

2

Be treated at a specialist centre

It is best to have surgery and plan treatment at a centre with a specialist gynaecological cancer team, especially if the disease is high risk or advanced [2].

3

Ask these questions

What type and grade is the tumour? What stage is it? What do the tumour's genetic tests (MMR, p53 and POLE) show? Will I need radiotherapy or chemotherapy after surgery?

4

If you want to become pregnant

Tell your doctor before surgery. In a specific group of young women, hormone treatment that keeps the womb for a while is possible [33]. In women under 45 with low-risk disease, the ovaries can sometimes be kept too [2].

5

Think about your family too

If your tumour is dMMR, you may need genetic counselling for Lynch syndrome; the result also helps your sisters, daughters and other relatives [2].

6

Regular follow-up

For high-risk disease you are usually examined every 3 months for the first 3 years and then every 6 months up to 5 years [10]. Tell your doctor promptly about any new symptom between visits [2].

7

Get back to healthy living

A healthy weight, physical activity, a balanced diet and stopping smoking are recommended; also talk to your doctor about sexual health, menopausal symptoms and any need for emotional support [2]. Read more: Exercise during treatment

Frequently asked questions

Is womb cancer different from cervical cancer?

Yes. Womb (endometrial) cancer starts in the inner lining of the body of the womb; the cervix is the lower, narrow part of the womb that opens into the vagina, and cancer there is a different disease [3]. The tests are different too: the smear test (Pap test) is for the cervix and does not find endometrial cancer [7].

Does bleeding after the menopause mean I have cancer?

Not necessarily. Fewer than 1 in 10 women who bleed after the menopause have womb cancer [5]. But because almost all patients with womb cancer have this symptom, any bleeding after the menopause should be checked promptly [5, 8].

Do I need a yearly ultrasound to prevent it?

For women at average risk without symptoms, no; no study has shown that regular ultrasound scans reduce deaths from this cancer [7]. The exception is women with Lynch syndrome, who have a special check-up plan [2].

Does keyhole (laparoscopic) surgery work as well as open surgery?

Yes. In two large studies, results with keyhole surgery were about the same as with open surgery [15, 16], with fewer complications and a shorter hospital stay [14]. The European guideline names keyhole surgery as the preferred approach, even for high-risk disease [2]. This is different from cervical cancer, where keyhole surgery gave worse results [17].

Are all the lymph nodes removed?

Usually not. With the "sentinel node" method, the first node or nodes that drain the womb are found with a special dye and removed [2]. In one study this method found almost all cases of spread to the nodes and can spare patients the side effects of removing all the nodes [18].

Will I go through the menopause after removal of the womb?

If you have not yet reached the menopause and your ovaries are removed too, yes. That is why, in women under 45 with low-risk disease, the ovaries are sometimes kept, as long as there is no inherited risk such as Lynch syndrome or a BRCA mutation [2]. Talk to your doctor about menopausal symptoms and how to manage them [2].

What is internal radiotherapy (brachytherapy)?

A small cylinder is placed in the vagina and the radiation reaches only the upper part of the vagina; in the main study this was 3 sessions one week apart [20]. It prevented the cancer coming back in the vagina as well as external radiotherapy to the pelvis did, with far fewer bowel side effects [19].

Does immunotherapy help every patient?

Not every patient. In advanced or recurrent disease it helps when given with chemotherapy, and much more so in dMMR tumours [26, 28]. But after complete surgery for high-risk disease, adding it to chemotherapy did not reduce the chance of the cancer coming back in patients overall [24]. Your doctor decides based on the stage and the MMR test.

Is womb cancer hereditary?

Sometimes. Lynch syndrome, which is inherited, greatly increases the risk [6]; that is why every patient's tumour is tested for MMR and, if needed, genetic counselling and testing are offered [2].

Evidence and recent advances (for doctors)

Show detailsHide
For physicians
HR 0.30
Progression or death with pembrolizumab + carboplatin–paclitaxel in dMMR
12-month progression-free survival 74% vs 38%; pMMR: HR 0.54; NRG-GY018 [26]
HR 0.69
Reduction in the risk of death with dostarlimab + chemotherapy in the overall population
dMMR/MSI-H: HR 0.32; RUBY, second interim analysis [29]
5%
Absolute gain in 5-year overall survival with chemoradiotherapy in high-risk disease
81.4% vs 76.1%; HR 0.70; stage III: 78.5% vs 68.5%; PORTEC-3 [22]
97.2%
Sensitivity of ICG sentinel node mapping for nodal disease
Negative predictive value 99.6%; FIRES [18]
For physicians

Surgery

Standard surgery for stage I and II disease is total hysterectomy with bilateral salpingo-oophorectomy and lymph node staging [II, A for stage I; IV, B for stage II]; infracolic omentectomy only for serous carcinoma, carcinosarcoma and undifferentiated carcinoma [IV, B]. Minimally invasive surgery is the preferred approach, including for high-risk disease [I, A]; any intraperitoneal tumour spillage, including rupture or morcellation (even in a bag), should be avoided [III, A] [2]. In LAP2 (2616 patients with clinical stage I to IIA), laparoscopy had fewer moderate-to-severe postoperative adverse events (14% vs 21%) and fewer hospital stays longer than 2 days (52% vs 94%); 74.2% of laparoscopies were completed without conversion [14]. The recurrence HR of 1.14 did not meet the prespecified non-inferiority criterion, but 3-year recurrence was 11.4% vs 10.2% and 5-year overall survival was 89.8% in both arms [15]. In LACE (760 patients with stage I endometrioid cancer), 4.5-year disease-free survival was 81.6% with laparoscopy and 81.3% with laparotomy (equivalence) [16]. This must not be confused with cervical cancer: in LACC, minimally invasive radical hysterectomy had lower 4.5-year disease-free survival (86.0% vs 96.5%) [17].

Sentinel lymph node biopsy is recommended for all patients with presumed uterus-confined disease [II, A]; ICG with cervical injection is the preferred technique; if no sentinel node is found on one side, side-specific systematic lymphadenectomy in high–intermediate and high risk [II, A]; all sentinel nodes should undergo ultrastaging [II, A] [2]. In FIRES (340 patients), at least one sentinel node was mapped in 86%; sensitivity was 97.2% and negative predictive value 99.6% [18]. Ovarian preservation can be considered in women under 45 with FIGO 2023 IA1 or IA2 and low risk by molecular classification, with bilateral salpingectomy, but not in carriers of BRCA mutations or Lynch syndrome [IV, B] [2]. In stage III and IV disease, cytoreduction (including removal of suspicious nodes) should be considered when complete resection is feasible with acceptable morbidity; systematic lymphadenectomy is not recommended [IV, B] [2].

For physicians

Adjuvant treatment: brachytherapy or external beam radiotherapy

In PORTEC-2 (427 patients with stage I or IIA high–intermediate-risk disease), 5-year vaginal recurrence was 1.8% with vaginal brachytherapy and 1.6% with external beam radiotherapy (HR 0.78), with no difference in overall survival (84.8% vs 79.6%) or disease-free survival; acute grade 1–2 gastrointestinal toxicity at the end of radiotherapy was 12.6% vs 53.8% [19]. At 10 years, vaginal recurrence was 3.4% vs 2.4% and overall survival 69.5% vs 67.6%; pelvic recurrence was more frequent with brachytherapy (6.3% vs 0.9%), mostly together with distant metastases; substantial LVSI, p53-mutant expression and L1CAM expression were risk factors for pelvic and distant recurrence, and external beam radiotherapy reduced pelvic recurrence in these cases [20].

Adjuvant treatment in high-risk disease

In PORTEC-3 (660 high-risk patients), chemoradiotherapy (two cycles of concurrent cisplatin followed by 4 cycles of carboplatin–paclitaxel) improved 5-year failure-free survival in the first final analysis (75.5% vs 68.6%; HR 0.71) but not overall survival significantly (HR 0.76); grade 3 or worse adverse events during treatment were 60% vs 12% [21]. In the updated analysis at a median follow-up of 72.6 months, 5-year overall survival was 81.4% vs 76.1% (HR 0.70; p=0.034) and failure-free survival 76.5% vs 69.1% (HR 0.70); the largest absolute benefit was in stage III (overall survival 78.5% vs 68.5%; HR 0.63) and serous cancers (71.4% vs 52.8%; HR 0.48); grade 2 or worse sensory neuropathy at 5 years was 6% vs 0% [22]. In the molecular analysis, the benefit of chemotherapy was significant only in p53abn (5-year recurrence-free survival 59% vs 36%), and POLEmut tumours did very well in both arms [13].

In GOG-258 (736 patients with stage III or IVA and residual disease of at most 2 cm), chemoradiotherapy did not improve relapse-free survival compared with 6 cycles of carboplatin–paclitaxel (59% vs 58% at 60 months; HR 0.90); vaginal recurrence (2% vs 7%) and pelvic and para-aortic nodal recurrence (11% vs 20%) were lower, but distant recurrence was higher (27% vs 21%) [23]. So in stage III both strategies are accepted: ESGO lists external beam radiotherapy with concurrent and adjuvant chemotherapy [I, A] and chemotherapy with or without brachytherapy as an alternative [I, B] [2].

For physicians
Adjuvant immunotherapy in all high-risk patients: a negative result

In KEYNOTE-B21 (1095 high-risk patients with no residual disease after surgery), adding pembrolizumab to adjuvant chemotherapy (with or without radiotherapy) did not improve disease-free survival (HR 1.02; 2-year disease-free survival 75% vs 76%), and grade 3 or worse adverse events were more frequent (71% vs 63%) [24]; the FDA label also records a "lack of effectiveness for adjuvant treatment" [37]. In the dMMR subgroup (281 patients) the HR was 0.31, and in pMMR 1.20 (prespecified subgroup analysis) [24]. ESGO considers adding an immune checkpoint inhibitor to adjuvant chemotherapy only in IIIm and IVAm MMRd disease [II, B] [2].

For physicians

Advanced or recurrent disease: first line

Carboplatin–paclitaxel has been the global standard since GOG-0209: in 1381 patients it was non-inferior to TAP (paclitaxel, doxorubicin and cisplatin) (median overall survival 37 vs 41 months; HR 1.002) and less toxic [25]. In four phase 3 trials, adding an immune checkpoint inhibitor to this regimen, followed by maintenance, improved progression-free survival, with the largest benefit in dMMR (table below) [26, 28, 30, 31].

In NRG-GY018, overall survival data are still immature, but the HRs favoured pembrolizumab (pMMR 0.79; dMMR 0.55) [27]. In RUBY, overall survival in the overall population was significantly better at the second interim analysis (HR 0.69); in pMMR/MSS the HR was 0.79 [29]. In DUO-E, adding olaparib to maintenance durvalumab gave more benefit in pMMR (HR 0.57 vs 0.77) [30]. In AtTEnd, the benefit of atezolizumab in the overall population was small, and interim overall survival did not cross the stopping boundary [31].

ESGO 2025: in MMRd, an immune checkpoint inhibitor (such as pembrolizumab, dostarlimab or durvalumab) with carboplatin–paclitaxel, followed by maintenance [I, A]; in non-MMRd with rapidly growing or symptomatic disease, carboplatin–paclitaxel [I, A], and adding an immune checkpoint inhibitor (such as pembrolizumab or dostarlimab), or an immune checkpoint inhibitor followed by maintenance with durvalumab and olaparib, can be considered [I, B]; the standard chemotherapy is 6 cycles of carboplatin–paclitaxel [I, A]. If chemotherapy is contraindicated and a non-MMRd patient has had previous adjuvant or neoadjuvant chemotherapy, pembrolizumab + lenvatinib [III, C]; in HER2 ‎3+‎ disease when immune checkpoint inhibitors are contraindicated, carboplatin–paclitaxel + trastuzumab [II, B]. In low-grade ER-positive tumours that are low volume, asymptomatic or slowly growing, endocrine therapy is preferred: progestogens (medroxyprogesterone or megestrol) [III, A], with aromatase inhibitors and tamoxifen as alternatives [IV, C] [2].

For physicians
Phase 3 trials of first-line immunotherapy with carboplatin–paclitaxel
TrialInterventionProgression-free survival in dMMRProgression-free survival in pMMR or overallOverall survival
NRG-GY018 [26, 27]Pembrolizumab for 6 cycles with chemotherapy, then maintenance every 6 weeks for up to 14 cycles12-month 74% vs 38%; HR 0.30pMMR: median 13.1 vs 8.7 months; HR 0.54Immature; pMMR HR 0.79, dMMR HR 0.55
RUBY [28, 29]Dostarlimab for 6 cycles with chemotherapy, then maintenance for up to 3 years24-month 61.4% vs 15.7%; HR 0.28Overall: 24-month 36.1% vs 18.1%; HR 0.64Overall HR 0.69 (significant); dMMR 0.32; pMMR 0.79
DUO-E [30]Durvalumab with chemotherapy, then durvalumab with or without olaparibHR 0.42 (durvalumab) and 0.41 (with olaparib)pMMR: HR 0.77 and 0.57; overall: 0.71 and 0.55Interim; overall HR 0.77 and 0.59
AtTEnd [31]Atezolizumab with chemotherapy for 6 to 8 cycles, then until progressionMedian not reached vs 6.9 months; HR 0.36Overall: median 10.1 vs 8.9 months; HR 0.74Interim: 38.7 vs 30.2 months; HR 0.82

There is no head-to-head comparison between these trials; eligibility, length of maintenance and timing of analyses differ. NRG-GY018 excluded carcinosarcoma, whereas AtTEnd included it. The MMR subgroup analyses in DUO-E were exploratory.

For physicians

Second line and beyond

In KEYNOTE-775 (827 patients after platinum-based chemotherapy), lenvatinib + pembrolizumab improved overall survival compared with doxorubicin or weekly paclitaxel in pMMR (median 17.4 vs 12.0 months; HR 0.68) and in all patients (18.3 vs 11.4 months; HR 0.62); grade 3 or worse adverse events were 88.9% vs 72.7% [32]. Single-agent pembrolizumab in MSI-H or dMMR disease after prior systemic therapy (KEYNOTE-158, 90 patients) gave an objective response rate of 46% with 12% complete responses [37]; single-agent dostarlimab is also FDA-approved for dMMR disease after a platinum-containing regimen [38].

ESGO 2025: in immunotherapy-naive patients, MMRd → immune checkpoint inhibitor monotherapy (pembrolizumab or dostarlimab) [III, A], with pembrolizumab + lenvatinib as an option [I, B]; non-MMRd → pembrolizumab + lenvatinib [I, A]. If this is not suitable, or the patient received immunotherapy in the first line: a platinum combination, doxorubicin, weekly paclitaxel or endocrine therapy [IV, B]; for HER2-overexpressing tumours, HER2-targeting strategies [II, B and III, B]. If feasible, MMR testing should be repeated on a sample of the recurrence [IV, B]. For locoregional recurrence without previous radiotherapy, external beam radiotherapy with or without brachytherapy and chemotherapy [IV, A], and for oligometastatic disease (1 to 5 lesions in up to 3 regions) local treatment [IV, B] [2].

Hormone therapy: in a GOG trial, oral medroxyprogesterone 200 mg daily gave a 25% response rate (17% complete) and 1000 mg daily was not better (15%); responses were more frequent in well-differentiated, progesterone receptor-positive tumours and only 8% to 9% in poorly differentiated or progesterone receptor-low tumours [34]. Everolimus + letrozole gave an objective response rate of 32% (9 complete responses among 35 patients) in a phase 2 study, and serous histology was the strongest predictor of no response [35]. In the randomised phase 2 GOG-3007 trial, the response rate was 22% with everolimus + letrozole and 25% with medroxyprogesterone alternating with tamoxifen; in chemotherapy-naive patients, median progression-free survival with everolimus + letrozole was 28 months, and grade 3–4 thromboembolic events occurred only with medroxyprogesterone/tamoxifen (11%) [36].

Treatment regimens and doses (for doctors)

Show detailsHide
Treatment regimens and doses: index19 regimens
For physicians
Shared safety points

Carboplatin: dose by the Calvert formula: total dose (mg) = target AUC × (GFR + 25); a cycle should not be repeated until neutrophils are at least 2000 and platelets at least 100,000 [42].

Paclitaxel: premedication for all patients: dexamethasone 20 mg orally about 12 and 6 hours before the infusion, diphenhydramine 50 mg IV and cimetidine 300 mg or ranitidine 50 mg IV 30 to 60 minutes before the infusion. Do not give if baseline neutrophils are below 1500; after severe neutropenia (below 500 for a week or longer) or severe peripheral neuropathy, reduce the dose of later cycles by 20% [43].

Immune checkpoint inhibitors (pembrolizumab, dostarlimab, durvalumab): determine MMR status with a validated test before starting [2]. No dose reductions are recommended; withhold for severe (grade 3) immune-mediated reactions, and discontinue permanently for grade 4 reactions, recurrent grade 3 reactions needing systemic immunosuppression, or inability to taper corticosteroids to 10 mg prednisone or less per day within 12 weeks [37, 38, 39]; grade 2 or higher myocarditis on pembrolizumab → permanent discontinuation [37]. On shared days, give pembrolizumab and dostarlimab before carboplatin and paclitaxel [37, 38].

Olaparib: blood counts at baseline and then monthly (MDS/AML in about 1.2% of patients across cancers); interrupt if pneumonitis is suspected and discontinue if confirmed; monitor for venous thromboembolism; avoid strong or moderate CYP3A inhibitors (if unavoidable, 100 or 150 mg twice daily); with creatinine clearance 31 to 50 mL/min, 200 mg twice daily [40].

Lenvatinib: control blood pressure before starting and monitor during treatment; withhold for grade 3 hypertension that persists despite optimal treatment and resume at a lower dose once controlled; discontinue permanently for grade 4 [41].

Progestogens: thrombophlebitis and pulmonary embolism (sometimes fatal) have been reported with megestrol, which should be used with caution in patients with a history of thromboembolism; it may worsen diabetes [44].

For physicians

After surgery: adjuvant radiotherapy and chemoradiotherapy

Vaginal brachytherapy (PORTEC-2)

Intermediate risk (preferred) or high–intermediate risk (alternative to external beam radiotherapy, especially pN0) after hysterectomyCycle length: Weekly

Intermediate risk (preferred) or high–intermediate risk (alternative to external beam radiotherapy, especially pN0) after hysterectomy

Before prescribing: Shared safety points
DrugDoseRouteSchedule
High-dose-rate (HDR) vaginal brachytherapy21 Gy in 3 fractions of 7 Gy, prescribed at 5 mm from the cylinder surfaceVaginal cylinder; upper half of the vaginaOne fraction per week
Cycle length
Weekly
Duration
3 fractions

In PORTEC-2, HDR was used in 85% of patients and 15% received an equivalent dose with LDR (0.5 to 0.7 Gy per hour) or MDR; radiotherapy started within 8 weeks of surgery [20]. LDR option in the original paper: 30 Gy [19]. ESGO: intermediate risk [I, A]; high–intermediate risk as an alternative to external beam radiotherapy [II, B] [2].

Evidence: PORTEC-2 (2010)

Pelvic external beam radiotherapy (PORTEC-2 and PORTEC-3)

High–intermediate risk (preferred); and the radiotherapy component of chemoradiotherapy in high-risk diseaseCycle length: Daily, 5 days a week

High–intermediate risk (preferred); and the radiotherapy component of chemoradiotherapy in high-risk disease

Before prescribing: Shared safety points
DrugDoseRouteSchedule
Pelvic external beam radiotherapy46 Gy in 23 fractions of 2 Gy (PORTEC-2); or 48.6 Gy in 1.8 Gy fractions (PORTEC-3)External beam, 3D-planned5 days a week
Cycle length
Daily, 5 days a week
Duration
23 to 27 fractions

Clinical target volume: proximal vagina, parametria, and internal, external and lower common iliac nodes [20]. In PORTEC-3 up to L5–S1, extended to the para-aortic region if nodes were involved; with cervical involvement, a brachytherapy boost equivalent to 14 Gy in 2 Gy fractions (suggested: 10 Gy HDR in 2 fractions of 5 Gy, at 5 mm depth); IMRT was allowed with approval, and 11 UK centres used 45 Gy [21].

Evidence: PORTEC-3 (2019), PORTEC-2 (2010)

Adjuvant chemoradiotherapy (PORTEC-3)

High risk (FIGO 2009): endometrioid IA grade 3 with LVSI, IB grade 3, II or III; or serous and clear cell stage I to III; WHO performance status 0 to 2

High risk (FIGO 2009): endometrioid IA grade 3 with LVSI, IB grade 3, II or III; or serous and clear cell stage I to III; WHO performance status 0 to 2

Before prescribing: Shared safety points
DrugDoseRouteSchedule
Concurrent with radiotherapy
Cisplatin50 mg/m²IVWeeks 1 and 4 of radiotherapy
Pelvic external beam radiotherapy48.6 Gy in 1.8 Gy fractionsExternal beam5 days a week
Then: 4 cycles
CarboplatinAUC 5IVDay 1 every 21 days
Paclitaxel175 mg/m²IVDay 1 every 21 days
Cycle length
Cisplatin in weeks 1 and 4 of radiotherapy; carboplatin–paclitaxel every 21 days
Duration
2 cycles of concurrent cisplatin, then 4 cycles of carboplatin–paclitaxel

Eligibility: white cells at least 3.0×10⁹/L, platelets at least 100×10⁹/L, bilirubin at most 1.5 times the upper limit, creatinine clearance above 60 mL/min; grade 2 or worse neuropathy was an exclusion criterion [22]. For toxicity, cisplatin was postponed by one week and stopped for grade 2 or worse neuropathy; paclitaxel was postponed for grade 2 neuropathy and stopped for grade 3 [21]. Grade 3 or worse adverse events during treatment: 60% [21].

Evidence: PORTEC-3 (2019)

Cisplatin and radiotherapy, then carboplatin–paclitaxel (GOG-258 chemoradiotherapy arm)

Stage III or IVA (FIGO 2009) with residual disease of at most 2 cm; or serous and clear cell stage I and II with positive peritoneal washings

Stage III or IVA (FIGO 2009) with residual disease of at most 2 cm; or serous and clear cell stage I and II with positive peritoneal washings

Before prescribing: Shared safety points
DrugDoseRouteSchedule
Concurrent with radiotherapy
Cisplatin50 mg/m²IVDays 1 and 29
Volume-directed external beam radiotherapy45 Gy in 25 fractions of 1.8 GyPelvis with or without para-aortic fields5 days a week
Then: 4 cycles
CarboplatinAUC 5 to 6IVDay 1 every 21 days
Paclitaxel175 mg/m²IVDay 1 every 21 days
Cycle length
Cisplatin on days 1 and 29 of radiotherapy; carboplatin–paclitaxel every 21 days
Duration
About 6 months (median 21 weeks)

With G-CSF support during carboplatin–paclitaxel; IMRT and vaginal cuff brachytherapy were allowed; 75% completed all 4 cycles [23]. This arm was not superior to chemotherapy alone but had fewer vaginal and pelvic recurrences [23].

Evidence: GOG-258 (2019)

Adjuvant carboplatin–paclitaxel, 6 cycles (GOG-258 chemotherapy arm)

Stage III or IVA after surgery; ESGO: chemotherapy with or without brachytherapy is an alternative to chemoradiotherapy in high-risk disease [I, B]Cycle length: Every 21 days

Stage III or IVA after surgery; ESGO: chemotherapy with or without brachytherapy is an alternative to chemoradiotherapy in high-risk disease [I, B]

Before prescribing: Shared safety points
DrugDoseRouteSchedule
CarboplatinAUC 6IVDay 1
Paclitaxel175 mg/m²IVDay 1
Cycle length
Every 21 days
Duration
6 cycles

85% of patients completed all 6 cycles in a median of 17 weeks; acute grade 4 or worse adverse events 30% vs 14% with chemoradiotherapy [23]. Place in the guideline: [2].

Evidence: GOG-258 (2019)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

For physicians

Advanced or recurrent disease: first line

Carboplatin + paclitaxel every 3 weeks

First line for unresectable stage III or IV disease or recurrence; non-MMRd with rapidly growing or symptomatic disease, or any patient not receiving immunotherapyCycle length: Every 21 days

First line for unresectable stage III or IV disease or recurrence; non-MMRd with rapidly growing or symptomatic disease, or any patient not receiving immunotherapy

Before prescribing: Shared safety points
DrugDoseRouteSchedule
Paclitaxel175 mg/m² (3-hour infusion)IVDay 1
CarboplatinAUC 5 to 6IVDay 1
Cycle length
Every 21 days
Duration
6 cycles [I, A]

Pan-Asian ESMO: carboplatin AUC 5 to 6 + paclitaxel 175 mg/m² every 21 days for 6 cycles is the first-line standard [I, A] [10]; ESGO also considers 6 cycles the standard [I, A] [2]. In GOG-0209 (carboplatin AUC 6 + paclitaxel 175 for 7 cycles), neutropenia was 80% and sensory neuropathy above grade 2 occurred in 20% [25]. 3-hour paclitaxel infusion as in NRG-GY018 [26].

Evidence: NRG-GY018 (KEYNOTE-868) (2023)

Pembrolizumab + carboplatin–paclitaxel (NRG-GY018)

First line: measurable stage III or IVA, IVB or recurrence; dMMR and pMMR; prior adjuvant chemotherapy allowed if at least 12 months earlier; ECOG 0 to 2; carcinosarcoma excluded

First line: measurable stage III or IVA, IVB or recurrence; dMMR and pMMR; prior adjuvant chemotherapy allowed if at least 12 months earlier; ECOG 0 to 2; carcinosarcoma excluded

Before prescribing: Shared safety points
DrugDoseRouteSchedule
With chemotherapy: 6 cycles every 21 days
Pembrolizumab200 mg (30-minute infusion)IVDay 1, before chemotherapy
Paclitaxel175 mg/m² (3-hour infusion)IVDay 1
CarboplatinAUC 5 (‎30-‎ to 60-minute infusion)IVDay 1
Maintenance: up to 14 cycles
Pembrolizumab400 mg (30-minute infusion)IVDay 1 every 6 weeks
Cycle length
21 days with chemotherapy, then 6 weeks
Duration
Up to 20 cycles of pembrolizumab (about 24 months), or until progression or unacceptable toxicity

Patients with measurable disease and a partial response or stable disease after cycle 6 could continue chemotherapy with pembrolizumab for up to 10 cycles at the investigator's discretion [26, 37]. FDA label: 200 mg every 3 weeks or 400 mg every 6 weeks with carboplatin–paclitaxel, regardless of MMR status, for up to 24 months [37]. Grade 3 or worse adverse events: dMMR 63.3% vs 47.2%; pMMR 55.1% vs 45.3% [26].

Evidence: NRG-GY018 (KEYNOTE-868) (2023)

Dostarlimab + carboplatin–paclitaxel (RUBY)

First line: primary stage III or IV or first recurrence; FDA indication regardless of MMR status

First line: primary stage III or IV or first recurrence; FDA indication regardless of MMR status

Before prescribing: Shared safety points
DrugDoseRouteSchedule
With chemotherapy: 6 cycles every 21 days
Dostarlimab500 mg (30-minute infusion)IVDay 1, before chemotherapy
CarboplatinAUC 5IVDay 1
Paclitaxel175 mg/m²IVDay 1
Maintenance
Dostarlimab1000 mgIVEvery 6 weeks
Cycle length
21 days for the first 6 cycles, then every 6 weeks
Duration
Until progression, unacceptable toxicity or up to 3 years

Dose source: the paper and the FDA label [28, 38]. Severe and serious adverse events were more frequent with dostarlimab; the most common adverse events were nausea (53.9%), alopecia (53.5%) and fatigue (51.9%) [28]. Regimen page: Dostarlimab with carboplatin–paclitaxel

Evidence: RUBY (ENGOT-EN6/GOG-3031) (2023)

Durvalumab + carboplatin–paclitaxel (DUO-E, dMMR)

First line for primary advanced or recurrent dMMR disease (FDA indication)

First line for primary advanced or recurrent dMMR disease (FDA indication)

Before prescribing: Shared safety points
DrugDoseRouteSchedule
With chemotherapy: 6 cycles every 21 days
Durvalumab1120 mg (60-minute infusion)IVDay 1
CarboplatinAUC 5 or 6IVDay 1
Paclitaxel175 mg/m²IVDay 1
Maintenance
Durvalumab1500 mgIVEvery 4 weeks
Cycle length
21 days for the first 6 cycles, then every 4 weeks
Duration
Until progression or unacceptable toxicity

Body weight below 30 kg: 15 mg/kg with chemotherapy, then 20 mg/kg every 4 weeks [39]. Dose source: the paper and the FDA label [30, 39].

Evidence: DUO-E (2024)

Durvalumab + carboplatin–paclitaxel, then durvalumab + olaparib (DUO-E, pMMR)

First line for primary advanced or recurrent disease; the benefit of adding olaparib was largest in pMMR; ESGO for non-MMRd [I, B]; olaparib has no endometrial cancer indication in the FDA labelEach drug’s schedule in the table

First line for primary advanced or recurrent disease; the benefit of adding olaparib was largest in pMMR; ESGO for non-MMRd [I, B]; olaparib has no endometrial cancer indication in the FDA label

Before prescribing: Shared safety points
DrugDoseRouteSchedule
With chemotherapy: 6 cycles every 21 days
Durvalumab1120 mgIVDay 1
CarboplatinAUC 5 or 6IVDay 1
Paclitaxel175 mg/m²IVDay 1
Maintenance
Durvalumab1500 mgIVEvery 4 weeks
Olaparib300 mg twice daily (tablets)OralDaily, continuously
Cycle schedule
Durvalumab every 3 weeks with chemotherapy, then every 4 weeks; olaparib daily and continuously during maintenance
Duration
Until progression or unacceptable toxicity

Dose source: full text of the paper [30]. Olaparib dose reductions: 250 mg, then 200 mg twice daily [40]. Grade 3 or worse adverse events: 67.2% over the whole treatment and 41.1% during maintenance [30].

Evidence: DUO-E (2024)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

For physicians

Advanced or recurrent disease: after platinum-based chemotherapy

Lenvatinib + pembrolizumab (KEYNOTE-775)

Progression after prior systemic therapy in any setting, not a candidate for curative surgery or radiotherapy; pMMR or not MSI-H (FDA indication); ESGO: non-MMRd without prior immunotherapy [I, A]Each drug’s schedule in the table

Progression after prior systemic therapy in any setting, not a candidate for curative surgery or radiotherapy; pMMR or not MSI-H (FDA indication); ESGO: non-MMRd without prior immunotherapy [I, A]

Before prescribing: Shared safety points
DrugDoseRouteSchedule
Lenvatinib20 mg once dailyOralDaily, continuously
Pembrolizumab200 mg (or 400 mg every 6 weeks per the label)IVDay 1 every 3 weeks
Cycle schedule
Lenvatinib daily and continuously; pembrolizumab every 3 weeks
Duration
Until progression or unacceptable toxicity; pembrolizumab for up to 24 months

Lenvatinib dose reductions: 14 mg, then 10 mg, then 8 mg daily; with creatinine clearance below 30 or severe hepatic impairment (Child-Pugh C), 10 mg daily [41]. In the label, hypertension 67% (grade 3–4: 39%) and hypothyroidism 67% [41]; grade 3 or worse adverse events in the trial 88.9% [32]. Regimen page: Lenvatinib with pembrolizumab

Evidence: KEYNOTE-775 (2022)

Single-agent pembrolizumab (MSI-H or dMMR)

Progression after prior systemic therapy, not a candidate for curative surgery or radiotherapy; no prior immunotherapy; ESGO [III, A]

Progression after prior systemic therapy, not a candidate for curative surgery or radiotherapy; no prior immunotherapy; ESGO [III, A]

Before prescribing: Shared safety points
DrugDoseRouteSchedule
Pembrolizumab200 mg every 3 weeks or 400 mg every 6 weeks (30-minute infusion)IVDay 1
Cycle length
Every 3 or every 6 weeks
Duration
Until progression, unacceptable toxicity or up to 24 months

KEYNOTE-158 (90 patients): objective response rate 46%, complete response 12%; 68% of responses lasted 12 months or longer [37].

Single-agent dostarlimab (dMMR)

dMMR recurrent or advanced disease progressing on or after a platinum-containing regimen, not a candidate for curative surgery or radiotherapy

dMMR recurrent or advanced disease progressing on or after a platinum-containing regimen, not a candidate for curative surgery or radiotherapy

Before prescribing: Shared safety points
DrugDoseRouteSchedule
First 4 cycles
Dostarlimab500 mg (30-minute infusion)IVEvery 3 weeks
Then
Dostarlimab1000 mgIVEvery 6 weeks
Cycle length
Every 3 weeks for the first 4 cycles, then every 6 weeks
Duration
Until progression or unacceptable toxicity

Dose source: FDA label [38].

Doxorubicin every 3 weeks (KEYNOTE-775 control arm)

After platinum-based chemotherapy, especially after first-line immunotherapy or when lenvatinib + pembrolizumab is not suitable [IV, B]Cycle length: Every 21 days

After platinum-based chemotherapy, especially after first-line immunotherapy or when lenvatinib + pembrolizumab is not suitable [IV, B]

Before prescribing: Shared safety points
DrugDoseRouteSchedule
Doxorubicin60 mg/m²IVDay 1
Cycle length
Every 21 days
Duration
Until progression or unacceptable toxicity, within the cumulative dose limit

Dose source: [32]; place in the guideline: [2]. The risk of cardiomyopathy rises with the cumulative dose (1% to 20% at cumulative doses of 300 to 500 mg/m² given every 3 weeks); check LVEF before and regularly during treatment [45].

Evidence: KEYNOTE-775 (2022)

Weekly paclitaxel (KEYNOTE-775 control arm)

After platinum-based chemotherapy [IV, B]Cycle length: Every 28 days

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

For physicians

Hormone therapy and fertility-sparing treatment

Oral medroxyprogesterone acetate

Low-grade, hormone receptor-positive advanced or recurrent disease, low volume or slowly growing [III, A]Cycle length: Daily, continuously

Low-grade, hormone receptor-positive advanced or recurrent disease, low volume or slowly growing [III, A]

Before prescribing: Shared safety points
DrugDoseRouteSchedule
Medroxyprogesterone acetate200 mg per dayOralDaily, continuously
Cycle length
Daily, continuously
Duration
Until progression or unacceptable toxicity

In the GOG trial, 200 mg per day gave a 25% response rate and 1000 mg per day 15%; there is no evidence for the higher dose [34]. Place in the guideline: [2].

Megestrol acetate

Low-grade, hormone receptor-positive advanced or recurrent disease [III, A]; label indication: palliative treatment of advanced endometrial carcinomaCycle length: Daily, continuously

Low-grade, hormone receptor-positive advanced or recurrent disease [III, A]; label indication: palliative treatment of advanced endometrial carcinoma

Before prescribing: Shared safety points
DrugDoseRouteSchedule
Megestrol acetate40 to 320 mg per day in divided dosesOralDaily, continuously
Cycle length
Daily, continuously
Duration
At least 2 months of continuous treatment to judge the effect; then until progression

Dose source: FDA label [44]. Place in the guideline: [2].

Letrozole + everolimus

Measurable recurrence after up to 2 prior cytotoxic regimens; largest benefit in endometrioid tumours and chemotherapy-naive patientsCycle length: 4-week cycles

Measurable recurrence after up to 2 prior cytotoxic regimens; largest benefit in endometrioid tumours and chemotherapy-naive patients

Before prescribing: Shared safety points
DrugDoseRouteSchedule
Letrozole2.5 mg once dailyOralDaily, continuously
Everolimus10 mg once dailyOralDaily, continuously
Cycle length
4-week cycles
Duration
Until progression, toxicity or complete response

Doses from phase 2 trials [35, 36]. Grade 3 anaemia in 24% and grade 3 mucositis in 5% [36].

Progestogen for fertility-sparing treatment

Grade 1 endometrioid, stage IA without myometrial invasion, in women who want to become pregnant; preferably after hysteroscopic resectionCycle length: Daily, continuously

Grade 1 endometrioid, stage IA without myometrial invasion, in women who want to become pregnant; preferably after hysteroscopic resection

Before prescribing: Shared safety points
DrugDoseRouteSchedule
One of these options
Megestrol acetate160 to 320 mg per dayOralDaily
Medroxyprogesterone acetate400 to 600 mg per dayOralDaily
Levonorgestrel-releasing intrauterine device52 mgIntrauterineAlone or with an oral progestogen
Cycle length
Daily, continuously
Duration
6 to 12 months; maximum 15 months to reach a complete response

ESGO/ESHRE/ESGE guideline: oral doses [III, B]; LNG-IUD 52 mg [III, B]; histological assessment by hysteroscopy every 3 to 6 months; after complete response, maintenance treatment until pregnancy is planned [II, A] [33].

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Scientific evidence

Show detailsHide

Key studies

7 items
Clinical trial

Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial

Lancet · 2010
1.8% vs 1.6%5-year vaginal recurrence
Summary
Clinical trial · Phase 3

Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial

Lancet Oncol · 2019
81.4% vs 76.1%5-year overall survival
Summary
Clinical trial · Phase 3

Adjuvant Chemotherapy plus Radiation for Locally Advanced Endometrial Cancer

N Engl J Med · 2019
59% vs 58%Alive and relapse-free at 60 months
Summary
Clinical trial · Phase 3

Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer

N Engl J Med · 2023
74% vs 38%dMMR: 12-month progression-free survival
Summary
Clinical trial · Phase 3

Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer

N Engl J Med · 2022
6.6 vs 3.8 monthsMedian progression-free survival (pMMR population)
Summary
Clinical trial · Phase 3

Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer

N Engl J Med · 2023
61.4% vs 15.7%dMMR/MSI-H: 24-month progression-free survival
Summary
Clinical trial · Phase 3

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

JCO · 2024
HR 0.71 (95% CI 0.57–0.89)Progression-free survival (all patients): durvalumab vs control
Summary

Clinical guidelines

1 item
Clinical guideline

ESGO-ESTRO-ESP guidelines for the management of patients with endometrial carcinoma: update 2025

Lancet Oncol · 2025
Summary

Common questions

Does obesity cause cancer?What are the symptoms of endometrial (womb) cancer?

Related drugs

Carboplatin (Paraplatin)Lenvatinib (Lenvima)Olaparib (Lynparza)Paclitaxel (Taxol)Pembrolizumab (Keytruda)Durvalumab (Imfinzi)

Treatment regimens (physicians)

Dostarlimab with carboplatin-paclitaxel in endometrial cancer (RUBY)Lenvatinib with pembrolizumab in endometrial cancer

References

45 references
Show all references, 9 with a study cardClose the reference list

Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.

  1. 1
    Endometrial cancerCrosbie EJ, Kitson SJ, McAlpine JN, et al · Lancet · 2022;399:1412-1428
    DOIPubMed Back to text: 1 2 3 4 5 6
  2. 2
    ESGO-ESTRO-ESP guidelines for the management of patients with endometrial carcinoma: update 2025Concin N, Matias-Guiu X, Cibula D, et al · Lancet Oncol · 2025;26:e423-e435
    Study cardDOIPubMed Back to text: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89
  3. 3
    What Is Endometrial Cancer?National Cancer Institute · cancer.gov · 2020
    Source Back to text: 1 2 3 4 5
  4. 4
    Endometrial Cancer SymptomsNational Cancer Institute · cancer.gov · 2020
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