Endometrial Cancer – Causes, Symptoms, Treatment

Endometrial cancer is the most common form of gynaecological cancer. Although symptoms usually appear even in the early stages, many women ignore them or mistake them for ordinary menstrual irregularities.

If endometrial cancer is detected early, the outlook is favourable. Among patients treated in the initial stages, the 5-year survival rate is over 80%. In this article we look at the causes and risk factors, the symptoms you shouldn't overlook, and the treatment options available today.

What is endometrial cancer

Endometrial cancer is a form of cancer that develops in the womb and affects the layer of cells forming the endometrium – the lining of the inside of the uterus, which thickens each month to support a possible pregnancy.

This type of cancer mainly affects women in middle or later life, with obesity being one of the most significant risk factors for the disease.

Unlike other gynaecological conditions, endometrial cancer usually produces visible symptoms even in the early stages, which is why early detection is possible. Much like endometriosis, endometrial cancer may present with abnormal vaginal bleeding, pelvic pain, discomfort when passing urine or during intercourse – signs that require prompt medical attention.

The difference between endometrial cancer and other forms of uterine cancer

Because the endometrium is the inner lining of the womb, some people use the term uterine cancer when they actually mean endometrial cancer. In reality, however, these are different conditions.

Endometrial cancer develops in the lining of the womb (the endometrium) and is the most common form of uterine cancer.

Other types of uterine cancer originate in the muscle tissue or in other supporting tissues of the womb. These are rarer and often more aggressive than endometrial cancer. Uterine sarcoma, for example, forms in the muscle of the womb. Cervical cancer develops in the cervix and has different causes, risk factors and prevention options.

The histological types of endometrial cancer

Depending on its microscopic appearance, aggressiveness and progression, endometrial cancer can be divided into several types. The histological type helps the doctor determine the most appropriate treatment and the prognosis. The main forms include:

• Endometrioid adenocarcinoma: this is the most common type of endometrial cancer and develops in the cells of the endometrial glands. It generally has a good prognosis, with slow progression and a good response to treatment, particularly when detected early.
• Serous adenocarcinoma: this form is more aggressive and requires more complex treatment, as it can spread quickly beyond the womb even in the early stages.
• Clear cell adenocarcinoma: a rare type of cancer with aggressive behaviour and a high risk of metastasis. The prognosis depends on the tumour grade and on how early the diagnosis is made.
• Mucinous carcinoma: a rarer form, characterised by excessive mucus production.
• Mixed carcinoma: involves two or more histological types, which may have different characteristics and require different treatment approaches.

Causes and risk factors of endometrial cancer

Although the exact causes of endometrial cancer are not known, specialists have identified a number of factors that significantly increase the risk of developing the disease.

What we know so far is that this type of cancer arises from a combination of genetic, environmental and hormonal factors that contribute to the abnormal development and uncontrolled multiplication of endometrial cells.

Hormonal imbalances and excess oestrogen

One of the most important factors involved is exposure to high levels of oestrogen without this being balanced by progesterone. This imbalance increases the risk of endometrial hyperplasia (excessive thickening of the womb lining) and, over time, may encourage malignant change.

Polycystic ovary syndrome or other ovarian disorders, hormone therapy without progesterone and a late menopause are among the situations associated with such excess oestrogen.

Obesity, diabetes and high blood pressure

Metabolic disorders have a considerable influence on hormonal health, and obesity is one of the leading risk factors for developing endometrial cancer. Fatty tissue produces additional amounts of oestrogen, and in obesity these levels can become far too high.

Diabetes and high blood pressure are also linked to chronic inflammation and hormonal disturbances that may increase the risk of endometrial cancer.

Age, menopause and nulliparity

The risk of endometrial cancer increases with age, particularly from the age of 50 onwards. Women who reach the menopause later, or those who had their first pregnancy late in life, are at greater risk because they have been exposed to oestrogen for longer.

Nulliparity (never having carried a pregnancy to term) is another risk factor, since pregnancy involves long periods of raised progesterone levels and natural hormonal protection for the endometrium.

Genetic factors: Lynch syndrome and family predisposition

Certain gene mutations considerably increase the risk of endometrial cancer. Lynch syndrome, for example, is an inherited condition that can raise the lifetime likelihood of developing this type of cancer to 20–60%.

A family history of endometrial, bowel or other tumours may also indicate a genetic predisposition and calls for closer monitoring.

Lifestyle and diet

Lack of exercise, a diet high in animal fats and a low fibre intake increase the risk of obesity, chronic inflammation and other hormonal imbalances linked to endometrial cancer.

The symptoms of endometrial cancer

Unlike other gynaecological cancers, endometrial cancer usually makes itself known even in the early stages. The sooner the signs are recognised and reported to a doctor, the earlier the diagnosis can be made and the greater the chances of effective treatment.

Abnormal vaginal bleeding

The most common symptom of endometrial cancer is abnormal vaginal bleeding.

In women who are still of reproductive age, there may be bleeding between periods, completely irregular cycles or very heavy bleeding requiring frequent changes of menstrual products.

In women who have been through the menopause, postmenopausal bleeding is the most common symptom. In such cases, even a single episode needs to be medically investigated.

Pelvic and abdominal pain

Persistent pain in the lower abdomen or the pelvic area may indicate local spread of the tumour or inflammation of the tissues near the womb. Although this pain can have many other causes, a medical assessment is important if it becomes persistent or severe.

Unusual vaginal discharge

Watery, pink, brown or blood-stained vaginal discharge with no obvious cause often appears before any pain begins. It is frequently overlooked, yet it may be a symptom of endometrial cancer.

Other general symptoms

In addition to the specific signs, some patients may experience general symptoms such as severe exhaustion, unexplained weight loss, bloating, pain during intercourse or swelling of the legs (due to compression of the lymph nodes). Chronic fatigue is also a common symptom associated with endometrial cancer.

Diagnosis and investigations for endometrial cancer

Diagnosing endometrial cancer involves a series of investigations that can detect changes in the womb lining and confirm the type of tumour. Early detection considerably improves the chances of effective treatment, which is why any unusual symptom should be assessed by a gynaecologist.

Gynaecological examination and transvaginal ultrasound

The first step in assessing a patient with suspected endometrial cancer is a full gynaecological examination.

Transvaginal ultrasound is often the first step, as it allows the doctor to assess the thickness of the endometrium and identify any structural changes. A visibly thickened endometrium, particularly in women who have been through the menopause, raises suspicion and calls for further investigation.

Endometrial biopsy and dilatation and curettage

A definitive diagnosis can only be made through histopathological examination of endometrial tissue. An endometrial biopsy is a minimally invasive procedure in which a small tissue sample is taken and examined under the microscope.

In some cases, particularly when suspicious changes are seen on ultrasound, the doctor may recommend dilatation and curettage – a method that allows a larger amount of tissue to be obtained and provides more accurate diagnostic results.

Imaging and tumour markers

Once the diagnosis is confirmed, the disease is staged – that is, the depth of invasion is determined and any metastases in the pelvis or abdomen are identified.

MRI allows assessment of infiltration into the myometrium and mapping of local spread, while CT scanning is useful for detecting possible metastases in the lymph nodes, the abdomen or the chest.

Although they are not specific to endometrial cancer, certain tumour markers such as CA125 and HE4 may be measured in advanced cases to monitor disease progression and response to treatment.

The stages of endometrial cancer

The cancer stage describes how far the disease has spread, and determining it is crucial in establishing the treatment plan.

In other words, when metastasis occurs, the cancer spreads from the endometrium to other areas of the body. Cancer cells can travel to other organs and form a metastatic tumour of the same type as the primary tumour. So if the cancer cells reach the lungs, for example, this is not lung cancer but metastatic endometrial cancer.

The medical literature distinguishes 4 stages of endometrial cancer:

• Stage I: tumour confined to the womb – this is the most common point of diagnosis and also the stage with the best prognosis. At this stage, the cancer is present only in the womb.
  • Only the endometrial cells and a small part of the muscle layer of the womb may be affected – this situation is classified as stage IA.
  • Half or more of the muscle layer of the womb may be affected – this situation is classified as stage IB.
• Stage II: involvement of the cervix – this stage means the tumour has spread from the womb to the tissue of the cervix, but has not yet gone beyond the structures of the uterus.
• Stage III: spread to the pelvic organs – at this point, the cancer has extended beyond the womb and cervix to the ovaries, fallopian tubes, vagina or pelvic lymph nodes, without, however, leaving the pelvic area. There are three substages of stage III:
  • Stage IIIA, when the cancer spreads outside the womb to the fallopian tubes, ovaries or the uterine ligaments.
  • Stage IIIB, when the cancer cells reach the vagina and/or the connective tissue around the vagina.
  • Stage IIIC, when the lymph nodes in the pelvis or alongside the aorta are affected.
• Stage IV: distant metastases – at this stage the cancer is present outside the pelvis and the cancer cells have spread to distant organs. Two phases of stage IV are distinguished:
  • Stage IVA, when the bladder or the bowel wall is affected.
  • Stage IVB, when the cancer reaches other organs such as the lungs or liver.

Tumour grade and the significance of the lymph nodes

Alongside the stages, the histological grade of the tumour plays a decisive role in the prognosis. It reflects how aggressive the disease is and indicates how closely the cancer cells still resemble healthy cells.

• Grade 1 (G1): the tumours are well differentiated and progress slowly.
• Grade 2 (G2): there is moderate differentiation between healthy and abnormal cells.
• High tumour grade (G3): the tumours are poorly differentiated, aggressive and carry an increased risk of spread.

Assessing the pelvic and para-aortic lymph nodes is an important step in correct staging, because the presence of cancer cells in these areas indicates a more advanced stage of disease and may change the treatment strategy.

Treatment options for endometrial cancer

Treatment for endometrial cancer depends on the stage of the disease, the histological type, the tumour grade, and the patient's age and general health. Treatment is usually complex and may involve surgery, radiotherapy, chemotherapy or modern, personalised therapies.

Surgical treatment of endometrial cancer – total hysterectomy

The most common procedure used to treat endometrial cancer involves removing the womb together with the cervix, the ovaries and the fallopian tubes (total hysterectomy) in order to prevent the disease from spreading. The operation can be performed as open surgery, laparoscopically or with robotic assistance.

Patients who undergo this procedure before reaching the menopause will no longer have periods and cannot become pregnant after a hysterectomy. In addition, night sweats, hot flushes and vaginal dryness may occur following the procedure.

Radiotherapy for endometrial cancer

Radiotherapy is mainly recommended after surgery for patients at increased risk of recurrence. It may be delivered as external beam radiotherapy or as internal radiotherapy to the vagina or cervix. The aim of treatment is to destroy any cancer cells remaining after the operation and to prevent the tumour from returning.

Chemotherapy and targeted therapies

Chemotherapy involves giving medicines to destroy cancer cells and is used in advanced stages (III–IV) or where there is a high risk of metastasis. The standard regimen combines carboplatin and paclitaxel, whose effectiveness in controlling the disease is well established.

In certain situations, the doctor may recommend targeted therapies that act on specific cancer cells. Compared with chemotherapy and radiotherapy, targeted therapy destroys only the cancer cells and not healthy cells. As a result, this form of treatment also does not cause side effects throughout the body.

Immunotherapy and modern treatments for endometrial cancer

In recent years, immunotherapy has emerged as a promising option, particularly for patients with MSI-H tumours or a DNA repair defect (dMMR).

The medicine pembrolizumab has shown favourable results in recurrent or advanced forms, by prompting the immune system to recognise and eliminate cancer cells.

Palliative and supportive care in endometrial cancer

For patients at advanced stages or with serious co-existing conditions, palliative care serves to improve quality of life. This includes measures to control pain and symptoms (bleeding, discharge, swelling), nutritional support, psychological counselling and emotional support.

This approach is essential for the patient's wellbeing and for maintaining a good quality of life – whatever the stage of the disease.

Progression and prognosis of endometrial cancer

The prognosis for endometrial cancer depends on a wide range of factors – from the stage at the time of diagnosis to the response to treatment.

Generally speaking, the disease has a favourable prognosis when detected early, since most cases produce early symptoms such as abnormal vaginal bleeding. Stage I also has the best long-term survival rate, as the tumour is confined to the womb and can be treated with a hysterectomy.

The histological type and tumour grade are also key factors. Aggressive or high-grade (G3) tumours may progress more quickly and carry an increased risk of recurrence.

The course of the disease varies from one patient to another, and the prognosis must be assessed individually, in collaboration with an oncologist and a specialist gynaecologist. A good response to treatment, regular check-ups and control of risk factors all contribute considerably to prolonging survival and improving quality of life.

Preventing endometrial cancer and ways to reduce your risk

As the causes are not precisely known, endometrial cancer is difficult to prevent. However, general preventive measures can be taken, such as controlling risk factors and monitoring gynaecological health, which lower the risk of disease and increase the chances of early detection:

• Controlling weight and metabolic conditions: obesity, diabetes and insulin resistance raise oestrogen levels, which encourages hyperplasia and malignant changes in the endometrium. A healthy weight, well-managed diabetes and blood pressure control are essential in reducing risk.
• Physical activity and a balanced diet: an active lifestyle helps maintain an optimal weight and reduces systemic inflammation. A nutrient-rich diet with plenty of vegetables, fruit, protein and healthy fats supports hormonal balance and helps lower the risk of endometrial cancer.
• Genetic counselling and hormone therapy: women with a family history of endometrial cancer, particularly those with Lynch syndrome, are advised to have genetic testing and specialist monitoring. Hormone therapy with progesterone or combined contraceptives can also reduce the risk of hyperplasia and endometrial cancer, but should only be taken on medical advice after weighing up the risks and benefits.

Frequently asked questions about endometrial cancer (FAQ)

Endometrial cancer – like any other cancer – is a diagnosis that can hit us hard and leave many uncertainties about symptoms, treatment options and the chances of recovery. It is important to discuss all these questions openly with your doctor, because a proper understanding of the condition can ease anxiety, aid early detection and guide well-informed decisions.

In the hope of offering you a little more clarity, we have put together below some brief, easy-to-understand answers to a few of the most common questions about endometrial cancer.

What is the difference between uterine cancer and endometrial cancer?

Endometrial cancer is the most common form of uterine cancer and develops in the lining of the womb (the endometrium). Other types of uterine cancer develop in the muscle tissue or other supporting tissues of the womb and have different causes, risk factors and prevention options.

Can endometrial cancer be prevented?

Endometrial cancer cannot always be prevented, but the risk can be reduced: by maintaining a healthy weight, controlling diabetes and high blood pressure, taking regular physical exercise, eating a balanced diet, using hormonal contraceptives as advised by a doctor, and having genetic monitoring where there is a family predisposition (e.g. Lynch syndrome).

What are the chances of recovery from endometrial cancer?

The prognosis depends on the histological type, the tumour grade and the response to treatment. For tumours confined to the womb (stage I), the 5-year survival rate is over 80%. This is precisely why seeing a doctor at the very first unusual signs is crucial for early detection.

Which investigations are needed to diagnose endometrial cancer?

Diagnosis involves a gynaecological examination and a transvaginal ultrasound, followed by an endometrial biopsy or dilatation and curettage for histopathological analysis, as well as imaging (MRI, CT) for staging. Tumour markers such as CA125 or HE4 may be helpful in advanced forms.

What treatments are available for advanced endometrial cancer?

In stages III–IV or in recurrent forms, chemotherapy, targeted therapies, immunotherapy, radiotherapy and palliative care may be recommended to relieve symptoms and improve quality of life.

How are patients monitored after treatment?

Follow-up involves regular gynaecological check-ups, assessment of symptoms, ultrasound or MRI scans, and blood tests including tumour markers. How often check-ups take place depends on the initial stage and the oncologist's recommendation, usually at shorter intervals during the first few years after treatment.

Can endometrial cancer come back?

Yes, endometrial cancer can recur, particularly with aggressive tumours or at advanced stages. For this reason, regular check-ups are recommended, as is promptly reporting any new symptoms (bleeding, pain, bloating).

What role does diet play in endometrial cancer?

A nutrient-rich diet with plenty of vegetables, fruit, wholegrains and protein, along with a moderate intake of animal fats, helps maintain a healthy weight and hormonal balance, and lowers the risk of endometrial cancer developing or returning.

What is a hysterectomy in endometrial cancer?

A hysterectomy is the surgical procedure in which the womb and often also the adnexa (ovaries and fallopian tubes) are removed. It is the mainstay of treatment for most patients; the approach may be open, laparoscopic or robotically assisted.

How often should gynaecological screening be carried out?

Women without major risk factors should have a gynaecological check-up once a year. Where there is a family history of endometrial cancer, Lynch syndrome or other hormonal conditions, the doctor may recommend more frequent check-ups and additional investigations.

Image source: Pexels.com