Endometrial Cancer

Original Editor - Muskan Rastogi Top Contributors - Muskan Rastogi, Candace Goh, Vidya Acharya and Alexandra Stead

Introduction

Endometrial cancer is a malignant tumour which originates within the epithelial lining of the uterus, known as the endometrium. It is the most common gynaecological cancer in high-income countries and the sixth most common cancer in women worldwide. Two principal histological subtypes are recognised: Type I (endometrioid), which accounts for approximately 80–90% of cases and is associated with oestrogen excess, and Type II (non-endometrioid), which is less common but carries a poorer prognosis. As survivorship improves, physiotherapists play an increasingly important role in managing treatment-related sequelae, including fatigue, lymphoedema, pelvic floor dysfunction, and reduced physical function.

Endometrial Cancer

Epidemiology

In 2022, there were approximately 420,368 new cases of endometrial cancer globally, with China, the United States, and Russia recording the highest number of cases. Although endometrial cancer predominantly affects peri- and postmenopausal women, with most cases diagnosed between the ages of 45 and 74, an increasing number of women of reproductive age are being diagnosed with the condition. Approximately 4% of women diagnosed with endometrial cancer are under the age of 40, and of these, around 70% are nulliparous.

Globally, the age-standardised incidence rate increased by 0.69% per year between 1990 and 2019. The estimated age-standardised incidence rates (ASRs) vary considerably across countries, with the highest rates found in nations with a very high Human Development Index (HDI), where corpus uteri cancer incidence is positively associated with HDI level. Low rates are observed in several Sub-Saharan African, Middle-Eastern, and South-Central Asian countries.

Endometrial cancer is one of the few cancers with rising mortality, with the death rate increasing by 1.6% per year from 2014 to 2023.

Stages

Stages of Endometrial Cancer

The system used for staging endometrial cancer is the 2023 FIGO (International Federation of Gynaecology and Obstetrics) system.

STAGE	SUBSTAGE	DESCRIPTION
I	IA	Disease limited to the endometrium OR non-aggressive histological type, i.e. low-grade endometroid, with invasion of less than half of myometrium with no or focal lymphovascular space involvement (LVSI) OR good prognosis disease IA1 Non-aggressive histological type limited to an endometrial polyp OR confined to the endometrium IA2 Non-aggressive histological types involving less than half of the myometrium with no or focal LVSI IA3 Low-grade endometrioid carcinomas limited to the uterus and ovary
I	IB	Non-aggressive histological types with invasion of half or more of the myometrium, and with no or focal LVSI
I	IC	Aggressive histological types limited to a polyp or confined to the endometrium
II	IIA	Invasion of the cervical stroma of non-aggressive histological types
II	IIB	Substantial LVSI of non-aggressive histological types
II	IIC	Aggressive histological types with any myometrial involvement
III	IIIA	Invasion of uterine serosa, adnexa, or both by direct extension or metastasis IIIA1 Spread to ovary or fallopian tube (except when meeting stage IA3 criteria) IIIA2 Involvement of uterine subserosa or spread through the uterine serosa
III	IIIB	Metastasis or direct spread to the vagina and/or to the parametria or pelvic peritoneum IIIB1 Metastasis or direct spread to the vagina and/or the parametria IIIB2 Metastasis to the pelvic peritoneum
III	IIIC	Metastasis to the pelvic or para-aortic lymph nodes or both IIIC1 Metastasis to the pelvic lymph nodes IIIC1i Micrometastasis IIIC1ii Macrometastasis IIIC2 Metastasis to para-aortic lymph nodes up to the renal vessels, with or without metastasis to the pelvic lymph nodes IIIC2i Micrometastasis IIIC2ii Macrometastasis
IV	IVA	Invasion of the bladder mucosa and/or the intestinal/bowel mucosa
IV	IVB	Abdominal peritoneal metastasis beyond the pelvis
IV	IVC	Distant metastasis, including metastasis to any extra- or intra-abdominal lymph nodes above the renal vessels, lungs, liver, brain, or bone

Risk Factors/Aetiology

Risk factors for endometrial cancer can be divided into modifiable and non-modifiable categories. Many are related to prolonged oestrogen exposure, metabolic dysfunction, and reproductive history. Understanding these risk factors is important for early identification and prevention. Key risk factors include:

• Obesity, type 2 diabetes, smoking, and physical inactivity.
• Insulin resistance has been positively correlated with endometrial cancer risk.
• Lower circulating levels of adiponectin and higher leptin levels have been related to a raised risk for endometrial cancer.
• Continuous exposure to oestrogen. ( hormone replacement therapy)
• Nulliparity.
• Tamoxifen.
• Polycystic Ovary Syndrome (PCOS).
• Lynch syndrome.
• Late menopause.

Clinical Presentation

The most common presenting symptom of endometrial cancer is abnormal uterine bleeding, which occurs in approximately 90% of cases. Other symptoms may include:

• Postmenopausal symptoms
• Abnormal vaginal discharge
• Pyometra (an accumulation of pus within the uterine cavity, which can occur secondary to obstruction of the cervical os by the tumour)
• Abdominal pain
• Abdominal distention

Assessment

Diagnosis of endometrial cancer involves a combination of clinical assessment, tissue sampling, and imaging. The following investigations are commonly used:

• Office-based pipelle sampling - An endometrial biopsy procedure performed quickly in the clinic without anaesthesia. A speculum is gently inserted into the vaginal opening to obtain a clear view of the cervix. A suction tube is then inserted to collect tissue samples, which are subsequently analysed in the laboratory. It is the recommended first-line investigation due to its simplicity and high diagnostic accuracy.
• Biopsy - A tissue sample taken from the endometrium for histological examination. It is used to confirm the diagnosis and determine the histological subtype and grade of the tumour, which inform staging and treatment planning.
• Dilation and curettage or hysteroscopy - A surgical procedure performed under anaesthesia in which the cervix is dilated and the uterine lining is scraped to obtain tissue for analysis. It is typically performed when pipelle sampling is inconclusive or insufficient.
• Magnetic Resonance Imaging (MRI) - The preferred imaging modality for preoperative staging, providing detailed assessment of myometrial invasion depth and cervical involvement.
• Transvaginal ultrasound - Used to measure endometrial thickness. An endometrial thickness of greater than 4–5mm in postmenopausal women warrants further investigation.

Non-Conservative Management

1.The traditional remedy for endometrial cancer is surgery involving

• Total hysterectomy with bilateral salpingo-oophorectomy
• Lymph node assessment
• Pelvic washings
• Pelvic and paraaortic lymphadenectomy

2. Radiotherapy

• Radiotherapy may be used as a primary treatment for those unfit for surgery, or as adjuvant therapy following surgery to reduce the risk of local recurrence. It may be delivered as external beam radiotherapy (EBRT) to the pelvis, or as vaginal brachytherapy, which targets the vaginal vault and is associated with fewer side effects.

3. Chemotherapy

• Chemotherapy is typically used in advanced or recurrent endometrial cancer, or in high-risk histological subtypes such as serous or clear cell carcinoma. Carboplatin and paclitaxel are the most commonly used agents. More recently, immunotherapy agents such as pembrolizumab have been incorporated into treatment protocols for tumours with mismatch repair deficiency.

Physiotherapy Management

Goals and Plans of Management

Physiotherapy plays an important role across the endometrial cancer care continuum, from pre-operative optimisation through to long-term survivorship. Management should be person-centred and tailored to the individual's treatment history, functional status, and goals of care. The key aims of physiotherapy management include:

• Counselling (e.g. diet requirements, about the condition etc.)
• To perform a complete urogynaecological assessment for protocol planning( pre, peri and post-operative assessment if possible).
• To increase physical activity.
• To increase strength and endurance.
• To reduce fatigue.
• To reduce lymphoedema after surgery. Physiotherapy management of lymphoedema can be read here.
• To plan a tailored exercise programme suitable for each individual.
• To prevent complications (for eg. urinary incontinence, weakening of pelvic floor muscles).
• To improve quality of life.

Pelvic Floor Rehabilitation

Surgery and radiotherapy for endometrial cancer frequently result in pelvic floor dysfunction, including urinary incontinence, bowel dysfunction, sexual dysfunction, and pelvic organ prolapse. Physiotherapists should conduct a thorough pelvic floor assessment pre- and post-operatively, and where indicated, deliver a structured pelvic floor muscle training (PFMT) programme tailored to the individual's symptoms and treatment history.

Pelvic floor rehabilitation may include:

• Pelvic floor muscle training to address urinary and bowel incontinence
• Vaginal dilator therapy following radiotherapy to manage vaginal stenosis
• Education on bladder and bowel habits
• Sexual rehabilitation and psychosexual support referral where appropriate
• Manual therapy and scar tissue management following surgery

Evidence supports the integration of pelvic floor and education-based therapies to improve bladder, bowel, vaginal, sexual, and psychological function, as well as overall quality of life in women treated for gynaecological cancer. Referral to a pelvic health physiotherapist should be considered for all women undergoing surgery or radiotherapy for endometrial cancer.

Exercise Program in Endometrial Cancer ; Feasibility and Acceptability Survivorship Trial (EPEC-FAST) Programme

People living with and beyond endometrial cancer face a high burden of treatment-related side effects, including fatigue, reduced physical function, weight gain, and increased cardiovascular risk. Many of these side effects are exacerbated by physical inactivity. Despite this, structured exercise programmes specifically designed for this population were largely absent prior to the development of EPEC-FAST. The EPEC-FAST was developed to address this gap, aiming to establish whether a supervised, personalised exercise intervention was feasible, acceptable, and beneficial for endometrial cancer survivors. EPEC-FAST programme consists of 60 minutes customised (one-to-one) training sessions with a personal trainer, once a week, for 10 consecutive weeks. It can be given to endometrial cancer survivors.

According to a study 79.5-85.8% of persons with endometrial cancer should be referred to a supervised exercise programme. Supervised exercise is particularly important in this population because many individuals present with co-morbidities such as obesity, type 2 diabetes, and cardiovascular disease, which require careful exercise prescription and monitoring. Supervised programmes ensure exercises are performed safely, at an appropriate intensity, and can be progressively adjusted in response to treatment side effects such as fatigue, lymphoedema, and reduced musculoskeletal function. Evidence suggests that structured physical activity improves cardiorespiratory fitness, reduces cancer-related fatigue, supports healthy weight management, and enhances overall quality of life in endometrial cancer survivors.

Exercise Phase	Descriptors
Warm-up
10 min	Low intensity warm-up using an exercise bike or a treadmill
Exercise phase
40 min	Aerobic exercise (20 min) Walking on a treadmill or cycling on an exercise bike. The exercise phase will be performed at a level of 40–60% of the maximum heart rate.
	Pillar strength training (10 min) Consists of 4 exercises to improve stability and strength of the hip, and 3 exercises to improve core stability and strength. Patients are recommended to perform 8 repetitions of each of the hip stability movements per leg, and a set of 10–15 repetitions of each core muscle exercise. A stability ball may be used to facilitate some of the exercises
	Hip movements: Hip flexion Hip extension Hip adduction Hip abduction	Core movements: Crunch Back Opposite arm/leg raise
	Resistance training (10 min) Consists of 1 set of 8 to 12 repetitions of 8 exercises that include all the major muscle groups. After initial phase of repetitions, this can be increased up to 20–25 repetitions (40–60% of 1 RM) during 1 session. A dumbbell, stability ball or bench may be used to facilitate the exercises. Exercises: Basic squat Lateral raise Dumb-bell deadlift Shoulder press Hamstring curl Dumb-bell biceps curl Overhead triceps extension Calf raise
Cool down
10 min	Set of 6 stretching and flexibility exercises. Four repetitions of each of the following muscle groups will be performed for10–30 s. Lower back Tensor fasciae latae Hip flexor Quadriceps Hamstring Calf

Follow-Up

When endometrial cancers recur, most are detected within the first 2 years after treatment. The person should undergo examination every 3 to 4 months for the first 2 years, every 6 months for the next 3 years, and yearly after 5 years. Vaginal cytology should be performed at least on yearly basis.