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Endometrial cancer

Endometrial cancer — recognising PMB and the GP pathway

By Dr HB Lo, FACRRM

- Reviewed 15 August 2026
- 10 min read

Endometrial cancer is Australia's most common gynaecological malignancy — about 3,300 new cases per year — with an 83 per cent five-year survival rate. The key symptom is postmenopausal bleeding (PMB): any vaginal bleeding after menopause, even one episode. About 1 in 10 women with PMB have endometrial cancer. Any episode warrants transvaginal ultrasound; if the lining exceeds 4 mm, endometrial biopsy follows.

Risk factors include obesity, diabetes, PCOS, Lynch syndrome, and tamoxifen. The GP role is to investigate promptly and refer to gynaecological oncology.

What endometrial cancer is and why early recognition matters

Endometrial cancer — also called uterine cancer or corpus uteri carcinoma — arises from the lining of the uterus (the endometrium). According to the Australian Institute of Health and Welfare, it is now the most common gynaecological cancer in Australia, with approximately 3,300 new cases diagnosed each year and about 660 deaths annually. Five-year survival sits at roughly 83 per cent — substantially better than ovarian cancer — because most women present while the cancer is still confined to the uterus.

The reason for this favourable profile is that endometrial cancer reliably produces a visible symptom early: postmenopausal bleeding. That window makes the GP role critical. Recognise the symptom, arrange urgent investigation, and refer promptly when findings are concerning.

Incidence has approximately doubled over thirty years, driven by rising rates of obesity and type 2 diabetes across the Australian population.

The Australian Cancer

Plan 2024–2033 formally recognises a two-week suspected-cancer pathway from GP presentation to transvaginal ultrasound and specialist consultation — a significant shift towards systematic early detection.

- Core clinical — the AU general-practice framework

The cardinal symptom: postmenopausal bleeding Cancer Australia’s 2024 guideline on postmenopausal bleeding and RANZCOG Clinical Guideline C-Gyn 39 are concordant: approximately 1 in 10 women with postmenopausal bleeding have endometrial malignancy.

Postmenopausal bleeding means any vaginal bleeding — spotting, blood-stained discharge, or frank bleeding — occurring 12 or more months after the last menstrual period. Every episode warrants investigation regardless of how minor it appears.

The most common causes are benign: vaginal atrophy (about 60 per cent of cases), endometrial polyps, and atrophic endometrium. But because roughly 10 per cent represent cancer, attributing bleeding to atrophy without imaging is clinically unsafe.

Women aged over 40 with heavy, persistent, or irregular uterine bleeding plus significant risk factors — obesity, type 2 diabetes, PCOS, Lynch syndrome family history, or tamoxifen use — also warrant lower-threshold investigation, even before menopause.

Additional Presentations That Require Assessment Include

- Persistent intermenstrual bleeding in women over 40
- Vaginal discharge that is watery or blood-stained in a postmenopausal woman
- Incidental finding of endometrial cells on cervical cytology in women aged 40 or over (cervical screening is not a tool for endometrial cancer detection, but this finding is reportable and requires separate endometrial assessment)

Investigation pathway in general practice Step 1: Transvaginal ultrasound. This is the first-line investigation, rebatable under MBS item 55070. The key measurement is the endometrial thickness measured as the maximum double-layer echo in the sagittal plane:

- ≤ 4 mm in a postmenopausal woman with PMB → atrophic endometrium likely; negative predictive value for endometrial cancer approximately 99 per cent per the Smith-Bindman JAMA 1998 meta-analysis. Biopsy is needed only if symptoms recur or persist despite a thin lining.
- > 4 mm → endometrial sampling is required.

Step 2: Endometrial biopsy. The Pipelle or Endocell office biopsy — a thin versátil catheter inserted through the cervix to sample cells from the uterine lining — is the standard first-line tissue test. Sensitivity for endometrial carcinoma is approximately 91 per cent in postmenopausal women. False-negative rate is roughly 10 per cent overall, rising to about 25 per cent for focal lesions (polyps, focal hyperplasia) where blind sampling may miss the abnormality. Cervical stenosis is the commonest reason for an inadequate sample in postmenopausal women.

Step 3: Hysteroscopy and curettage. Arranged by a gynaecologist when the Pipelle sample is inadequate, when ultrasound shows a focal intracavitary lesion, or when bleeding persists despite a negative biopsy. This is the definitive tissue test with direct visualisation of the endometrial cavity.

What To Include Alongside The Referral

- Transvaginal ultrasound report and images
- Biopsy histology where available
- Full blood count, blood glucose or HbA1c, serum ferritin if anaemic
- Current medication list, especially hormone therapy or tamoxifen
- BMI and blood pressure
- Three-generation family pedigree if Lynch syndrome is suspected

What not to order routinely: CA-125 is not a screening or diagnostic test for endometrial cancer. It is non-specific and should be reserved for staging of confirmed high-grade tumours or suspected extra-uterine spread.

Examination

Weight and BMI (recalculate explicitly — clinically relevant to risk stratification and management), blood pressure, abdominal palpation for masses, and pelvic examination including speculum inspection to exclude visible cervical or vaginal pathology. Cervical screening if due.

- Risk factors and the two biological pathways

Endometrial cancer is not one disease. The original pathological framework of Bokhman 1983, refined by the Cancer Genome Atlas molecular classification, describes two dominant biological pathways with distinct risk profiles, histologies, and prognoses. Type 1 — endometrioid (approximately 80 per cent of cases)

Driven by chronic unopposed oestrogen stimulation of the endometrial lining.

The biological sequence: anovulation or oestrogen excess → endometrial proliferation → hyperplasia → grade 1 endometrioid adenocarcinoma. Anything that prolongs oestrogen exposure without adequate progestogen opposition raises risk:

Risk factor Approximate relative risk BMI ≥ 30 ~3× BMI ≥ 40 ~5–7× Type 2 diabetes ~2× (independent of BMI) PCOS with chronic anovulation Elevated (unopposed oestrogen) Tamoxifen use ~2–3× Oestrogen-only hormone therapy (intact uterus) Substantially elevated Late menopause after age 55 Elevated Nulliparity, early menarche Moderately elevated

Protective factors include parity, breastfeeding, and combined oral contraceptive use (approximately 30 per cent risk reduction per decade of use through sustained progestogen opposition).

Type 2 — non-endometrioid (approximately 20 per cent of cases)

Includes serous, clear cell, and carcinosarcoma histologies. These arise independently of oestrogen exposure, carry near-universal TP53 mutations, and behave more aggressively — often presenting at an advanced stage despite the uterus appearing to be a site of minimal bleeding. Anti-oestrogen strategies are ineffective; chemotherapy and radiotherapy are the treatment cornerstones.

Lynch syndrome — the hereditary pathway

Lynch syndrome (germline mutations in MLH1, MSH2, MSH6, PMS2, or EPCAM) is the most clinically important hereditary endometrial cancer risk. Lifetime endometrial cancer risk is 40–60 per cent. In female Lynch carriers, endometrial cancer is frequently the sentinel cancer — the first Lynch-related malignancy to present, often before bowel cancer.



Ask explicitly about a family history of endometrial, colorectal, gastric, ovarian, urothelial, or sebaceous cancers across three generations.

eviQ protocols and Cancer Council Australia now recommend universal mismatch repair immunohistochemistry (MLH1, MSH2, MSH6, PMS2) on all endometrial cancer specimens at diagnosis. When protein loss is found without an MLH1 promoter methylation explanation, cascade germline genetic testing is offered to first-degree relatives via a Family Cancer Clinic.

Cowden syndrome (PTEN hamartoma tumour syndrome) carries a 28 per cent lifetime endometrial cancer risk and warrants surveillance.

- Treatment and what to expect after diagnosis

Once endometrial cancer is confirmed histologically, management transfers to a gynaecological oncology multidisciplinary team. The GP role shifts to community coordination, comorbidity management, and survivorship support. Staging investigations — specialist-ordered
- Pelvic MRI to assess myometrial invasion depth and cervical stromal involvement
- CT chest, abdomen, and pelvis for suspected or advanced-stage disease
- Molecular subtype profiling — POLE mutation testing, mismatch repair immunohistochemistry, p53 staining — increasingly informs adjuvant therapy intensity decisions and is embedded in the FIGO 2023 staging revision

FIGO staging at diagnosis in Australia: approximately 70 per cent Stage I (confined to uterus), 10 per cent Stage II, 15 per cent Stage III, 5 per cent Stage IV.

Surgery

Laparoscopic total hysterectomy with bilateral salpingo-oophorectomy is the standard for most cases, with shorter hospital stay and lower wound infection rates than open surgery. Pelvic and para-aortic lymph node assessment guides adjuvant therapy decisions.

Adjuvant treatment

Guided By FIGO Stage And Molecular Subtype

- Low-risk Stage I: surgery alone
- Intermediate-risk: vaginal brachytherapy (localised pelvic radiotherapy)
- High-risk and Stage III–IV: external-beam radiotherapy plus carboplatin and paclitaxel chemotherapy

Immune checkpoint inhibitors for advanced disease Immune checkpoint inhibitors have transformed treatment for advanced and recurrent endometrial cancer. Pembrolizumab combined with lenvatinib (KEYNOTE-775, NEJM 2022) significantly improved progression-free and overall survival versus chemotherapy alone in women with recurrent or advanced disease. Pembrolizumab combined with carboplatin and paclitaxel (NRG-GY018, NEJM 2023) is now first-line for advanced disease and is available on the Pharmaceutical Benefits Scheme (PBS Authority Required, Section 100), with greatest benefit in tumours showing mismatch repair deficiency.

Fertility-sparing treatment For carefully selected women — grade 1, Stage IA endometrioid tumours without myometrial invasion, who wish to preserve fertility — high-dose progestogen therapy (medroxyprogesterone acetate or levonorgestrel-releasing intrauterine system) is an option. This requires specialist supervision and close hysteroscopic surveillance given recurrence risks.

- Australian operations

MBS items for general practice
- Consultations — items 23/36/44 (Level B/C/D); Level C or D is appropriate for a new postmenopausal bleeding workup with risk-factor inventory and referral co-ordination
- Transvaginal ultrasound — item 55070
- Lynch syndrome germline testing — item 73296 (proband) and item 73297 (cascade testing first-degree relatives), Authority Required; pre-test genetic counselling is recommended per RACGP Genomics guidance
- Mental Health Care Plan — items 2715/2717 for cancer-related distress and adjustment disorders (very common across the treatment journey)
- ATSI Health Assessment — item 715: incorporate proactive postmenopausal bleeding enquiry at every Aboriginal and Torres Strait Islander Health Assessment

Referral pathway The Australian Cancer Plan 2024–2033 stipulates a two-week suspected-cancer pathway from GP presentation to transvaginal ultrasound and specialist consultation. Document clinical suspicion explicitly in referral letters and include the TVUSS report, biopsy histology, medication list, BMI, and family pedigree. All postmenopausal bleeding with endometrial thickness > 4 mm, persistent symptoms regardless of endometrial thickness, atypical hyperplasia on biopsy, or confirmed malignancy → gynaecological oncology multidisciplinary team.

eviQ hosts current AU-specific endometrial cancer treatment protocols. ANZGOG coordinates clinical trials across Australia and New Zealand.

Survivorship in general practice

After treatment, the GP role includes: managing lymphoedema after pelvic lymphadenectomy; supporting sexual function post-radiotherapy (vaginal dilators, pelvic floor physiotherapy, non-hormonal lubricants); surveillance for Lynch-related second malignancies (colonoscopy every one to two years, urinary cytology and ultrasound); comorbidity loop (weight, glycaemic control, blood pressure, lipids, vaccination, bone health after bilateral salpingo-oophorectomy, mood); and cancer-related fatigue and distress support.

- Special populations

Aboriginal and Torres Strait Islander women. Higher all-cancer mortality and documented gaps in stage at presentation and access to specialist services are described by the AIHW. Proactive postmenopausal bleeding enquiry at every contact and ATSI Health Assessment is warranted. Coordinate with Aboriginal Community Controlled Health Organisations; Closing the Gap PBS Co-payment applies to post-treatment medications. Lynch syndrome carriers. RACGP Genomics guidance and eviQ protocols recommend annual endometrial ultrasound assessment from age 35, and discussion of risk-reducing total hysterectomy plus bilateral salpingo-oophorectomy at ages 35–40 after childbearing is complete. Refer to a Family Cancer Clinic for genetic counselling and a structured surveillance plan.

Premenopausal women. Endometrial cancer in women under 50 is uncommon (approximately 15 per cent of cases) but occurs in the context of obesity, PCOS with chronic anovulation, and Lynch syndrome. Heavy or persistent irregular uterine bleeding in women over 40 with significant risk factors warrants endometrial assessment at lower threshold than in younger women.

Elderly women. Older women may attribute postmenopausal bleeding to non-uterine causes or delay presentation. Maintain a high index of clinical suspicion. Frailty and comorbidity influence treatment intensity discussions but do not preclude appropriate investigation and specialist review.

Tamoxifen users. Annual clinical review for symptoms of abnormal uterine bleeding is standard practice for all women taking tamoxifen. Routine screening TVUSS in asymptomatic tamoxifen users is not recommended due to high false-positive rates from tamoxifen-induced subepithelial cystic changes that mimic endometrial thickening; however, any symptomatic bleeding warrants investigation as with non-tamoxifen users.

When to escalate

Refer promptly or arrange emergency assessment in the following situations:

- Any postmenopausal bleeding → urgent transvaginal ultrasound within two weeks (suspected-cancer pathway)
- Endometrial thickness > 4 mm on TVUSS → same-week gynaecological oncology referral
- Atypical hyperplasia or endometrial intraepithelial neoplasia on biopsy → urgent gynaecological oncology (approximately 30–40 per cent have concurrent endometrial cancer at hysterectomy)
- Persistent symptoms despite negative Pipelle biopsy → hysteroscopy via gynaecology




- Suspected postmenopausal pyometra (uterine fluid collection) → urgent referral (strong association with endometrial malignancy)
- Heavy bleeding with haemodynamic compromise → emergency department
- MMR protein loss on tumour immunohistochemistry → Family Cancer Clinic for germline testing and cascade counselling

What this article is and is not This is general health information drawn from Cancer Australia, RANZCOG, AIHW, Cancer Council Australia, eviQ, and peer-reviewed clinical trials. It does not constitute personal medical advice and does not establish a doctor–patient relationship. Decisions about investigation, biopsy, referral, and treatment are made with your own GP and specialist gynaecological oncology team.

For Australian consumer resources: Cancer Council 13 11 20 — Uterine cancer, Jean Hailes for Women’s Health, HealthDirect — Uterine cancer, ANZGOG patient information, and Inherited Cancers Australia for Lynch families.

For cancer-related distress: Cancer Council helpline 13 11 20, Beyond Blue 1300 22 4636.

Sources cited

- Cancer Australia — Investigation of postmenopausal bleeding (2024)
- AIHW — Cancer data in Australia (2024)
- RANZCOG — C-Gyn 39: Investigation of postmenopausal bleeding
- Cancer Council Australia — Uterine cancer
- HealthDirect — Uterine cancer
- eviQ — Endometrial cancer treatment protocols
- ANZGOG
- Jean Hailes for Women’s Health
- RACGP — Genomics in general practice
- Australian Cancer Plan 2024–2033
- Smith-Bindman R et al. — Endovaginal ultrasound to exclude endometrial cancer (JAMA 1998)
- Makker V et al. — KEYNOTE-775: pembrolizumab plus lenvatinib (NEJM 2022)
- Eskander RN et al. — NRG-GY018: pembrolizumab plus chemotherapy (NEJM 2023)
- Luo J et al. — Intentional weight loss and endometrial cancer risk (JCO 2017)
- NICE NG12 — Suspected cancer: recognition and referral

Frequently asked questions
- What counts as postmenopausal bleeding and why does it matter? Postmenopausal bleeding means any vaginal bleeding — including light spotting or blood-stained discharge — occurring 12 or more months after the last menstrual period. About 1 in 10 women with postmenopausal bleeding have endometrial cancer, while most have benign causes such as vaginal atrophy or a polyp. Because the proportion with cancer is meaningful, every episode warrants medical assessment within two weeks. Even a single episode of light spotting should not be attributed to atrophy without first arranging a transvaginal ultrasound to measure the endometrial lining.
- What investigations will my GP arrange? The first test is a transvaginal ultrasound to measure the endometrial thickness. If the lining is thicker than 4 mm in a postmenopausal woman, an endometrial biopsy is required — a brief in-rooms procedure using a thin sampling tube (Pipelle or Endocell). If the biopsy is inadequate, or if a focal lesion is seen on ultrasound, a gynaecologist will arrange a hysteroscopy and curettage under anaesthetic. Routine blood tests include a full blood count and glucose. CA-125 is not a routine endometrial cancer test and should not be used as a screening or rule-out measure.
- What are the main risk factors for endometrial cancer? The dominant risk factors relate to chronic oestrogen exposure without adequate progestogen opposition: obesity raises risk three to five times through peripheral oestrogen production in fat tissue; type 2 diabetes independently doubles the risk; PCOS with chronic anovulation prolongs unopposed oestrogen exposure; late menopause, early menarche, and nulliparity accumulate lifetime exposure; tamoxifen (used in breast cancer treatment) partially stimulates the endometrium; and oestrogen-only hormone therapy taken by women who retain their uterus substantially elevates risk unless adequately opposed with progestogen.
- What is Lynch syndrome and why does it matter for endometrial cancer? Lynch syndrome is an inherited condition caused by a defect in a DNA mismatch repair gene (MLH1, MSH2, MSH6, PMS2, or EPCAM). It carries a 40 to 60 per cent lifetime risk of endometrial cancer, often presenting as the first Lynch-related malignancy in women — before bowel cancer. Pathologists now routinely test every endometrial cancer specimen for mismatch repair protein loss. When loss is found without a methylation explanation, cascade genetic testing is offered to family members. Lynch carriers may discuss risk-reducing hysterectomy and bilateral salpingo-oophorectomy after completing their family, from around age 35 to 40.
- What treatment options are available if I am diagnosed? Early-stage endometrial cancer confined to the uterus is usually treated by laparoscopic hysterectomy with removal of both fallopian tubes and ovaries. Some Stage I tumours require surgery alone; higher-risk tumours receive vaginal brachytherapy with or without chemotherapy based on molecular subtype. Advanced or recurrent disease is now treated with immune checkpoint inhibitors — pembrolizumab combined with lenvatinib, or with carboplatin and paclitaxel chemotherapy — both available on the Pharmaceutical Benefits Scheme, with the greatest benefit in tumours showing mismatch repair deficiency.
- Can I reduce my risk of endometrial cancer? Yes. Sustained weight loss of 5 to 10 per cent reduces risk by lowering peripheral oestrogen production. Optimising blood sugar control in type 2 diabetes also helps, with observational data suggesting metformin provides an additional risk-modulating effect. Women with an intact uterus taking systemic oestrogen hormone therapy must have adequate progestogen to protect the endometrial lining — this is non-negotiable. The oral contraceptive pill taken for five or more years reduces lifetime risk by roughly 30 per cent per decade of use. Lynch carriers should discuss risk-reducing surgery with a gynaecological oncologist from around age 35 to 40.

Source quality Sources grouped by evidence tier. AU primary tier first; international where AU is silent or lagging; named-author reconstruction where guidelines have not yet caught up. How tiers work.
- T1 AU primary 10 sources
- Cancer Australia — Investigation of postmenopausal bleeding (2024)
- AIHW — Cancer data in Australia (2024 update)
- RANZCOG — Investigation of postmenopausal bleeding (C-Gyn 39)
- Cancer Council Australia — Uterine cancer
- HealthDirect — Uterine cancer
- eviQ — Endometrial cancer treatment protocols and Lynch syndrome surveillance
- ANZGOG — Australia New Zealand Gynaecological Oncology Group
- Jean Hailes for Women's Health
- RACGP — Genomics in general practice
- Australian Cancer Plan 2024–2033

- T2 International primary 1 source

- NICE NG12 — Suspected cancer: recognition and referral

- T3 Named-author reconstruction 4 sources

- Smith-Bindman R et al. — Endovaginal ultrasound to exclude endometrial cancer (JAMA 1998)
- Makker V et al. — Pembrolizumab plus lenvatinib in advanced endometrial cancer (KEYNOTE-775, NEJM 2022)
- Eskander RN et al. — Pembrolizumab plus chemotherapy in advanced endometrial cancer (NRG-GY018, NEJM 2023)
- Luo J et al. — Intentional weight loss and endometrial cancer risk (JCO 2017)

Where to next
- The Tiredness Workup — if tiredness is part of your picture: a free tool that helps you prepare for a thorough GP conversation. No card, no sign-up to start.
- Patient tools — free, private tools for preparing questions, decoding results, and mapping decisions with your GP.
- Work with me — The Workup membership: the weekly member-deep work-up, the 12-week pathway, and the monthly live call.

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📌 Endometrial cancer — recognising PMB and the GP pathway (Mazatlán)
🏢 Dr Hb Lo
📍 Mazatlán