Endometrial cancer is the most common form of gynecological cancer, and although symptoms usually appear in the early stages, many women ignore them or confuse them with regular menstrual disorders.

Diagnosed early, endometrial cancer has a favorable prognosis. In patients treated in the early stages, the 5-year survival rate is over 80%. In this article, we talk about causes and risk factors, the manifestations that you should not ignore, and what treatment options exist today.

What is endometrial cancer?

Endometrial cancer is a form of cancer that begins to develop in the uterus, affecting the layer of cells that form the endometrium, the mucous membrane that lines the inside of the uterus and that thickens every month to support a possible pregnancy.

This type of cancer occurs especially in middle-aged or elderly people, and obesity is among the main risk factors associated with this pathology.

Unlike other gynecological conditions, endometrial cancer usually has visible symptoms in its early stages, which is why early detection is possible. Like endometriosis , endometrial cancer can manifest itself through abnormal vaginal bleeding, pain in the pelvic region, discomfort when urinating or during sexual intercourse, signs that require immediate medical attention.

The difference between endometrial cancer and other types of uterine cancer

Because the endometrium is the inner lining of the uterus, some people use the term uterine cancer when referring to endometrial cancer. In reality, these are describing different conditions.

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

Other types of uterine cancer arise in the muscle or other supporting tissues of the uterus. They are rarer and often more aggressive than endometrial cancer. Uterine sarcoma, for example, forms in the muscles of the uterus. Cervical cancer begins in the cervix and has different causes, risk factors, and prevention methods.

Histological types of endometrial cancer

Depending on the microscopic appearance, aggressiveness and evolution, endometrial cancer can be classified into several types. The histological type helps the doctor determine the most appropriate treatment and prognosis. Among the main forms are:

• Endometrioid adenocarcinoma : This is the most common type of endometrial cancer and forms in the endometrial gland cells. It generally has a good prognosis, with slow progression and good response to treatment, especially when detected early.
• Serous adenocarcinoma: represents a more aggressive form and requires more complex treatment because it can spread quickly outside the uterus, even in early stages.
• Clear cell adenocarcinoma: A rare type of cancer with aggressive behavior and a high risk of metastasis. The prognosis depends on the tumor grade and how early it is diagnosed.
• Mucinous carcinoma: is a rarer form, characterized by excessive mucus production.
• Mixed carcinoma: involves two or more histological types that may have different characteristics and require diverse therapeutic approaches.

Causes and risk factors of endometrial cancer

Although the causes of endometrial cancer are not exactly 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 occurs as a result of a combination of genetic, environmental, and hormonal factors, which contribute to the abnormal development and uncontrolled multiplication of endometrial cells.

Hormonal imbalances and excess estrogen

One of the main factors involved is exposure to high estrogen levels without being counterbalanced by progesterone. This imbalance increases the risk of endometrial hyperplasia (excessive thickening of the endometrium) and may favor malignant transformation over time.

Polycystic ovary syndrome or other ovarian disorders, progesterone-free hormone therapy, and late menopause are among the situations associated with such estrogen excess.

Obesity, diabetes and hypertension

Metabolic disorders have a major impact on hormonal health, and obesity is one of the main risk factors associated with the development of endometrial cancer. Adipose tissue produces additional amounts of estrogen, and its levels can become too high in case of obesity.

Diabetes and hypertension are also associated with chronic inflammation and hormonal imbalances that can increase the risk of endometrial cancer.

Age, menopause and nulliparity

The risk of endometrial cancer increases with age, especially after age 50. Women who enter menopause later or have their first pregnancy later are at higher risk because they have had longer exposure to estrogen.

Nulliparity (lack of a completed pregnancy) is another risk factor, as pregnancy involves long periods of elevated progesterone levels and natural hormonal protection for the endometrium.

Genetic factors: Lynch syndrome and familial predisposition

Certain genetic mutations significantly increase the risk of endometrial cancer. Lynch syndrome, for example, is an inherited condition that can increase the likelihood of developing this type of cancer to 20-60% over a lifetime.

Also, family history of endometrial, colon, or other types of tumors may signal a genetic predisposition and require closer monitoring.

Lifestyle and nutrition

Sedentary lifestyle, diet high in animal fats, and low fiber intake increase the risk of obesity, chronic inflammation, and other hormonal imbalances associated with endometrial cancer.

Symptoms of endometrial cancer

Unlike other types of gynecological cancer, endometrial cancer tends to manifest itself in its early stages. The sooner the signs are recognized and reported to the doctor, the sooner the patient can receive a diagnosis and increase her chances of effective treatment.

Abnormal vaginal bleeding

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

In women still in their reproductive years, bleeding between periods, completely irregular cycles, or very heavy periods requiring frequent changes of menstrual products may occur.

For people going through menopause, postmenopausal bleeding is the most common symptom. In these situations, even a single occurrence should be investigated medically.

Pelvic and abdominal pain

Persistent pain in the lower abdomen or pelvic area may signal local tumor growth or inflammation of the tissues near the uterus. Although this pain can have many other causes, it is important to seek medical evaluation when it becomes constant or intense.

Atypical vaginal discharge

Watery, pink, brown, or bloody vaginal discharge, without an obvious cause, often occurs before pain sets in. It is often overlooked, but it can be a symptom of endometrial cancer.

Other general symptoms

In addition to specific signs, some patients may experience general symptoms such as extreme fatigue, unexplained weight loss, bloating, pain during intercourse , and leg swelling (due to lymph node compression). 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 allow the identification of changes in the uterine lining and confirmation of the type of tumor. Early detection considerably improves the chances of effective treatment, which is why any unusual symptom should be evaluated by a gynecologist.

Gynecological consultation and transvaginal ultrasound

The first step in evaluating a patient with suspected endometrial cancer is a complete gynecological consultation.

Transvaginal ultrasound is often the first step, as it allows the doctor to assess the thickness of the endometrium and identify any structural abnormalities. A visibly thickened endometrium, especially in postmenopausal women, raises suspicion and requires further testing.

Endometrial biopsy and uterine curettage

A definitive diagnosis can only be made by histopathological analysis of endometrial tissue. An endometrial biopsy is a minimally invasive procedure in which a small tissue sample is collected for microscopic examination.

In some cases, especially if suspicious changes are observed on ultrasound, the doctor may recommend uterine curettage, a method that allows for the removal of a larger amount of tissue and provides more accurate diagnostic results.

Imaging and tumor markers

Once the diagnosis is confirmed, the disease is staged, namely the establishment of invasion and the detection of possible metastases in the pelvis or abdomen.

MRI allows the evaluation of myometrial infiltration and the identification of local extension, while computed tomography is useful for detecting possible metastases to the lymph nodes, abdomen or chest.

Although not specific to endometrial cancer, certain tumor markers such as CA125 and HE4 can be evaluated in advanced cases, in monitoring the progression of the disease and response to treatment.

Stages of endometrial cancer

The stage of cancer describes the extent of the disease, and identifying it is essential for establishing the treatment plan.

In other words, when it reaches metastasis, the cancer begins to spread from the endometrium to other parts of the body. The cancer cells can travel to other organs and form a metastatic tumor of the same type as the primary tumor. So, if the cancer cells reach the lungs, for example, it will not be lung cancer, but metastatic endometrial cancer.

In the literature, 4 stages of endometrial cancer have been identified:

• Stage I: Tumor confined to the uterus - this is the most common time of diagnosis and also the stage with the best prognosis. At this stage, the cancer is present only in the uterus.
  • Only endometrial cells and a small part of the muscle layer of the uterus may be affected, a situation classified as stage IA .
  • Half or more of the muscle layer of the uterus may be affected, a situation classified as stage IB .
• Stage II: Cervical invasion - this stage indicates that the tumor has spread from the uterus to the cervical tissue, but has not yet gone beyond the uterine structures.
• Stage III: Extension to pelvic organs - in this stage, the cancer has spread beyond the uterus and cervix to the ovaries, fallopian tubes, vagina, or pelvic lymph nodes, but not beyond the pelvic area. There are three stages of stage III, namely:
  • Stage IIIA , when the cancer extends outside the uterus to the fallopian tubes, ovaries, or ligaments of the uterus.
  • Stage IIIB , when cancer cells reach the vagina and/or the connective tissue around the vagina.
  • Stage IIIC, when lymph nodes in the pelvis or aorta are affected.
• Stage IV: Distant metastases - cancer is present outside the pelvis at this stage, with cancer cells having spread to distant organs. Two phases of stage IV have been identified:
  • Stage IVA, when the bladder or bowel wall is affected.
  • Stage IVB, when the cancer reaches other organs, such as the lungs or liver.

Tumor grade and importance of lymph nodes

In addition to stages, a crucial role in determining prognosis is played by the histological grade of the tumor. This reflects the aggressiveness of the disease, determining how much the cancer cells resemble healthy ones.

• Grade 1 (G1): tumors are well differentiated, having a slow evolution.
• Grade 2 (G2): There is moderate differentiation between healthy and cancerous cells.
• High tumor grade (G3): tumors are poorly differentiated, aggressive, and at high risk of spreading.

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

Treatment options for endometrial cancer

The treatment of endometrial cancer is determined by the stage of the disease, histological type, tumor grade, age and general condition of the patient. Most often, the therapy is complex and involves surgery, radiotherapy, chemotherapy or modern personalized treatments.

Surgical treatment for endometrial cancer – total hysterectomy

The most common intervention for treating endometrial cancer is the removal of the uterus along with the cervix, ovaries, and fallopian tubes (total hysteroscopy) to prevent the spread of the disease. The operation can be performed using a classic, laparoscopic, or robotic approach.

Patients who undergo this procedure before menopause will no longer have periods and will not be able to get pregnant after the hysterectomy. They may also experience night sweats, hot flashes, and vaginal dryness after the procedure.

Radiotherapy in endometrial cancer

Radiotherapy is recommended especially after surgery, in patients with a high risk of recurrence. External radiotherapy can be performed, or internal radiotherapy to the vagina or cervix. The goal of the treatment is to destroy any cancer cells remaining after surgery and to prevent the tumor from recurring.

Chemotherapy and targeted therapies

Chemotherapy consists of administering drugs to destroy cancer cells and is used in advanced stages (III–IV) or when there is a high risk of metastasis. The standard treatment regimen includes the combination of carboplatin and paclitaxel, with proven effectiveness in controlling the disease.

In some cases, your doctor may recommend targeted therapies that target specific cancer cells. Unlike chemotherapy and radiation therapy, targeted therapy only kills cancer cells, not healthy cells. Because of this, this type of treatment doesn't cause side effects throughout the body.

Immunotherapy and modern treatments for endometrial cancer

In recent years, immunotherapy has become a promising option especially for patients with MSI-H or DNA repair deficiency (dMMR) tumors.

The drug pembrolizumab has demonstrated favorable results in recurrent or advanced forms, stimulating the immune system to recognize and eliminate cancer cells.

Palliative and supportive treatment for endometrial cancer

For patients in advanced stages or with severe comorbidities, palliative treatment aims to improve quality of life. It includes ways to manage pain and symptoms (bleeding, discharge, edema), nutritional support, psychological counseling, and emotional support.

This type of approach is essential for the patient's comfort and for maintaining a good quality of life, regardless of the stage of the disease.

Evolution and prognosis of endometrial cancer

The prognosis of endometrial cancer depends on a multitude of factors, from the stage at the time of diagnosis to the response to treatment.

The disease generally has a favorable prognosis when detected early, as most cases present with early symptoms such as abnormal vaginal bleeding. Stage I also has the best long-term survival rate, due to the tumor being confined to the uterus and the possibility of treatment with hysterectomy.

Histological type and tumor grade are also essential factors. Aggressive or high-grade tumors (G3) may have a faster progression and an increased risk of recurrence.

The evolution of the disease differs from one patient to another, and the prognosis must be assessed individually, in collaboration with an oncologist and a specialized gynecologist. Good response to treatment, regular monitoring and control of risk factors contribute significantly to prolonging survival and improving quality of life.

Endometrial cancer prevention and risk reduction measures

Because the exact causes are not known, endometrial cancer is difficult to prevent. However, general preventive measures, such as controlling risk factors and monitoring gynecological health, can reduce the risk of developing the disease and increase the chances of early detection:

• Weight and metabolic disease control: Obesity, diabetes, and insulin resistance increase estrogen levels, which favors endometrial hyperplasia and malignant transformation. Maintaining a healthy weight, managing diabetes, and controlling blood pressure are essential to reduce risk.
• Physical activity and balanced diet: An active lifestyle supports maintaining an optimal weight and reducing systemic inflammation. A nutritious diet, rich in vegetables, fruits, proteins and healthy fats supports hormonal balance and helps reduce the risk of endometrial cancer.
• Genetic evaluation and hormonal therapy: Women with a family history of endometrial cancer, especially those with Lynch syndrome, are recommended to undergo genetic evaluation and specialized monitoring. Also, hormone therapy with progesterone or combined contraceptives may reduce the risk of endometrial hyperplasia and cancer, but should be administered only on the recommendation of a doctor, after assessing the risks and benefits.

Frequently asked questions about endometrial cancer (FAQ)

Endometrial cancer, like any other cancer, is a diagnosis that can affect us deeply and leave us with a lot of uncertainty about symptoms, treatment options, and chances of recovery. It is important to discuss all these concerns openly with your doctor, as a proper understanding of the disease can reduce anxiety, aid in early detection, and guide informed decisions.

In the hope of providing you with a little more clarity, we have prepared succinct and accessible answers to some of the most frequently asked questions about endometrial cancer below.

What is the difference between uterine cancer and endometrial cancer?

Endometrial cancer is the most common type of uterine cancer and occurs in the lining of the uterus (endometrium). Other types of uterine cancer occur in the muscle tissue or other supporting tissues of the uterus and have different causes, risk factors, and prevention methods.

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 hypertension, regular physical activity, a balanced diet, using hormonal contraceptives as recommended by a doctor, and genetic monitoring in cases with a family predisposition (e.g. Lynch syndrome).

What are the chances of cure in endometrial cancer?

The prognosis depends on the histological type, tumor grade, and response to treatment. For tumors located in the uterus (stage I), the 5-year survival rate exceeds 80%. That is why a visit to the doctor at the first unusual signs is essential for early detection.

What investigations are necessary for the diagnosis of endometrial cancer?

Diagnosis involves a gynecological consultation and a transvaginal ultrasound, followed by endometrial biopsy or uterine curettage for histopathological analysis and imaging investigations (MRI, CT) for staging. Tumor markers such as CA125 or HE4 may be useful in advanced forms.

What treatments are there for advanced endometrial cancer?

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

How are patients monitored after treatment?

Post-treatment monitoring involves regular gynecological check-ups, symptom assessment, ultrasound or MRI scans, and blood tests with tumor markers. The frequency of check-ups depends on the initial stage and the recommendation of the oncologist, usually at shorter intervals in the first years after treatment.

Can recurrence occur in endometrial cancer?

Yes, endometrial cancer can recur, especially in aggressive tumors or in advanced stages. This is why regular monitoring and prompt reporting of any new symptoms (bleeding, pain, bloating) are recommended.

What role does diet play in endometrial cancer?

A nutritious diet, rich in vegetables, fruits, whole grains and proteins, with a balanced intake of animal fats, contributes to maintaining a healthy weight and hormonal balance, reducing the risk of the occurrence and recurrence of endometrial cancer.

What is hysterectomy in endometrial cancer?

Hysterectomy is the surgical procedure that removes the uterus and, often, the adnexa (ovaries and fallopian tubes). It is the primary treatment for most patients, and the approach can be classical, laparoscopic, or robotic.

How often should gynecological check-ups be performed for prevention?

Women without major risk factors should have annual gynecological checkups. For those with a family history of endometrial cancer, Lynch syndrome, or other hormonal conditions, your doctor may recommend more frequent monitoring and additional investigations.

Photo source: Pexels.com