Endometrial Cancer

21.03.2024

ENDOMETRIUM CANCER DIAGNOSIS AND TREATMENT

Endometrial cancer is a type of cancer that originates from the endometrium, the inner layer of the uterus, and is one of the most common cancers affecting the female reproductive system. Although it is usually seen in post-menopausal women, it can occur in women of all age groups. The most common symptoms of this type of cancer include abnormal vaginal bleeding, pelvic pain, and abnormal vaginal discharge. Endometrial cancer is often treatable when diagnosed early, so it is of great importance that any post-menopausal vaginal bleeding is taken seriously and evaluated. Treatment usually begins with surgery and radiotherapy, hormone therapy or chemotherapy is added when necessary. Risk factors include conditions such as obesity, long-term estrogen exposure, early onset of menstruation, late menopause, infertility, and polycystic ovary syndrome. The importance of this type of cancer is due to the fact that it is a common cancer that affects women's health and early diagnosis has a great impact on the success of treatment. Therefore, it is critical for women to have regular gynecological examinations and be aware of risk factors.

WHAT ARE THE RISK FACTORS?

Endometrial cancer is a type of cancer that originates from the endometrium, the inner layer of the uterus, and some risk factors may increase the likelihood of developing this type of cancer. Although each of these risk factors is not a definitive cause for the development of cancer, their presence may increase the risk.

Known risk factors of endometrial cancer include:

Age: The risk increases with age, and it is especially common in postmenopausal women.

Obesity: The risk of endometrial cancer increases in women with a high body mass index. Excess body fat leads to more estrogen production in the body.

Long-Term Estrogen Exposure: Factors such as early onset of menstruation, late menopause, and taking estrogen therapy (without progesterone) increase the body's long-term exposure to estrogen.

Never Giving Birth: Not having given birth may increase the risk.

Hormone Therapy: Taking estrogen therapy after menopause may increase risk, especially when not balanced with progesterone.

Polycystic Ovary Syndrome (PCOS): Conditions that cause hormonal imbalance, such as PCOS, may increase the risk.

Family History of Cancer: The risk is especially increased in families with a history of colon cancer (also known as Lynch syndrome) or uterine cancer.

Cancer History: Having had other types of estrogen-related cancer, such as breast cancer or ovarian cancer, may cause risk.

High Blood Pressure and Diabetes: These health problems can also increase the risk.

Endometrial Hyperplasia: Abnormal thickening of the inner lining of the uterus is known as endometrial hyperplasia, which can turn into cancer.

The presence of these risk factors does not necessarily mean that endometrial cancer will develop. However, being aware of risk factors, regular screenings and health checks are important for early diagnosis of this cancer. Women with any risk factors are recommended to discuss these risks and possible screening methods with their doctor.

Image 1: Endometrial cancer occurs in the tissues on the inner surface of the uterus.

HOW DOES IT OCCUR?

Endometrial cancer originates from the endometrium, the inner lining of the uterus, and is often associated with hormone imbalances. The mechanism of development of this cancer depends especially on the excessive effect of the estrogen hormone. Under normal circumstances, there is a balance between estrogen and progesterone, but when this balance is disrupted, estrogen can cause endometrial cells to grow excessively, which can turn into cancer. Genetic factors may also play a role; For example, some genetic mutations (e.g. PTEN, KRAS, or P53 gene mutations) can lead to uncontrolled division of endometrial cells and cancer. Endometrial hyperplasia is an abnormal thickening of the endometrium, which increases the risk of it turning into cancer. In addition, the presence of endometrial cancer or other related cancers (e.g. Lynch syndrome) in the family is also a risk factor. In short, the development of endometrial cancer is the result of a series of interactions such as hormonal effects, genetic predispositions and environmental factors. Understanding these factors is important for early diagnosis and development of effective treatment strategies.

WHAT ARE THE SYMPTOMS?

Endometrial cancer is a type of cancer that originates from the inner layer of the uterus and can present with certain findings. Being aware of these findings is important for early diagnosis and treatment. The most common findings of endometrial cancer are:

Abnormal Vaginal Bleeding: Any vaginal bleeding in postmenopausal women is the most obvious and common symptom. In premenopausal women, excessive or irregular menstrual bleeding can also be a sign.

Pelvic Pain: There may be pain or discomfort in the lower abdomen or pelvic area.

Abnormal Vaginal Discharge: Abnormal vaginal discharge that may be colorless, watery or bloody may occur.

Pain During Intercourse: Pain or discomfort may be detected during sexual intercourse.

Bloating or Pressure Feeling in the Abdominal Area: It can be seen especially when the cancer progresses.

Forced Urination or Defecation: There may be difficulty or pain during urination or defecation.

Rapid Weight Loss and Loss of Appetite: General health symptoms that can be seen in advanced stage cancer may be observed.

These symptoms may not be specific to endometrial cancer and may be caused by other health problems. However, if you have any one or more of these symptoms, it is important to contact a healthcare professional immediately, especially in post-menopausal women. Early diagnosis plays a critical role in successfully treating endometrial cancer.

HOW IS IT DIAGNOSED?

Diagnosing endometrial cancer is an extensive process that typically involves a series of steps. It usually begins in patients presenting with symptoms such as abnormal vaginal bleeding after menopause. The first step is a gynecological examination and especially the evaluation of endometrial tissue. The most common diagnostic test is endometrial biopsy; In this procedure, a small tissue sample is taken from the inner layer of the uterus and examined under a microscope. Transvaginal ultrasound can be used for more detailed evaluation; This images the thickness and structure of the uterus and endometrium. When necessary, hysteroscopy may be performed for a more comprehensive evaluation and treatment; In this procedure, a small camera is inserted into the uterus and tissue samples can be taken from abnormal areas. In advanced cases, imaging tests such as computed tomography (CT) or magnetic resonance imaging (MRI) may be performed to determine the spread and stage of the cancer. These steps are used together to determine the presence, type, and spread of endometrial cancer, allowing the most appropriate treatment approach to be determined for the patient. The diagnostic process is personalized based on the patient's symptoms and medical history, and each step provides information critical to treatment planning.

WHAT ARE THE PATHOLOGICAL TYPES?

Endometrial cancer originates from the endometrium, the inner layer of the uterus, and is divided into different pathological types. These types are determined according to the cellular characteristics and histological structure of the cancer. The main pathological types of endometrial cancer are:

Endometrioid Adenocarcinoma: Endometrioid adenocarcinoma, the most common type, accounts for the majority of endometrial cancers. It is usually related to estrogen and its well-differentiated form has a better prognosis.

Serous Adenocarcinoma: It is a more aggressive type and may have a poor prognosis. This type usually occurs in postmenopausal women and is associated with genetic mutations such as p53.

Clear Cell Carcinoma: It is a rare type and may also have a poor prognosis. Clear cell carcinoma is usually diagnosed in more advanced stages.

Muköz Adenocarcinoma: It is also a rare type and originates from mucus-producing cells. This type may sometimes require a different treatment approach than endometrioid adenocarcinoma.

Squamous Cell Carcinoma: It is a very rare type of endometrial cancer and usually has a poor prognosis.

Mixed Types and Other Rare Types:Some endometrial cancers may involve more than one cell type or belong to rarer types (for example, undifferentiated or neuroendocrine tumors).

Each pathological type affects the behavior of the cancer, its response to treatment, and the patient's prognosis. Therefore, pathological diagnosis plays an important role in treatment planning and patient management. Diagnosis is usually made by microscopic examination of surgically removed tissue samples, and this examination helps determine the most appropriate treatment strategy.Treatment and prognosis of endometrial cancer are determined depending on the biological characteristics of the tumor, and among these features, the presence of some receptors is particularly important. Some of the most considered receptors in this type of cancer are estrogen and progesterone receptors (ER and PR). The presence of these receptors in endometrial cancer cells indicates that the disease may respond to hormone therapy and is generally associated with a better prognosis. Additionally, some types of endometrial cancer may be positive for the HER2/neu receptor, which may affect the response to targeted therapies. Mutations in the p53 tumor suppressor gene and changes in Mismatch Repair (MMR) genes can also affect the behavior of cancer and determine the response to treatments such as immunotherapy. Analysis of these receptors and molecular markers helps develop personalized approaches to the treatment of endometrial cancer and create treatment plans appropriate to each patient's situation.

Image 2: A biopsy of the uterus is required to diagnose endometrial cancer.

HOW IS TUMOR STAGING DONE?

Tumor staging in endometrial cancer is a process used to determine the extent of cancer spread and plays an important role in determining treatment options and prognosis. Staging for endometrial cancer is usually done according to criteria set by FIGO (International Federation of Gynecology and Obstetrics). This staging system is classified as follows:

Stage I: Cancer is found only in the endometrium (the inner lining of the uterus).

Stage IA: Cancer is found in less than half of the myometrium.

Stage IB: Cancer affects more than half of the myometrium.

Stage II:The cancer has spread to the connective tissue of the cervix (cervix), but has not spread outside the uterus.

Stage III: The cancer has spread outside the uterus but remains in the lower part of the abdominal cavity.

Stage IIIA: Cancer has spread to the uterine serosa or adnexa (ovaries and fallopian tubes).

Stage IIIB: Spread to vaginal and/or pelvic lymph nodes.

Stage III C: Cancer has spread to the pelvic and/or para-aortic lymph nodes.

Stage IV: The cancer has spread beyond the lower part of the abdominal cavity.

Stage IVA: Cancer has spread to the bladder and/or bowel mucosa.

Stage IV: It has metastasized to distant organs (liver, lungs, etc.).

This staging is generally supported by pathological examination of tissue samples taken by surgical intervention, imaging methods such as ultrasound, magnetic resonance imaging (MRI), computerized tomography (CT) and, if necessary, biopsy. Staging results are used to determine treatment options and the patient's prognosis. Each stage shows different characteristics that indicate the spread and severity of cancer, and treatment approaches are determined according to this staging.

HOW IS TREATMENT DONE ACCORDING TO STAGES?

Endometrial cancer treatment varies depending on the stage of the cancer and is tailored to each patient's individual needs. Below, general treatment approaches are summarized according to the stages of endometrial cancer:

Stage I:

Surgery: The most common treatment approaches are total abdominal hysterectomy (removal of the uterus) and bilateral salpingo-oophorectomy (removal of both ovaries and fallopian tubes).

Radiotherapy: In some cases, pelvic radiotherapy may be recommended to prevent local recurrence after surgery.

Stage II:

Surgery: Hysterectomy and bilateral salpingo-oophorectomy are generally preferred at this stage.

Radiotherapy: Extended pelvic radiotherapy and brachytherapy (radiation therapy placed inside the uterus) may be applied after surgery.

Chemotherapy: In some cases, especially in high-risk patients, chemotherapy is added as adjuvant therapy.

Stage III:

Surgery: Surgery also plays an important role in stage III cancers.

Radiotherapy: After surgery, extended pelvic radiotherapy and brachytherapy are often used.

Chemotherapy: In stage III cancers, adjuvant chemotherapy can be used to prevent or delay disease recurrence.

Stage IV:

Palliative Surgery and Radiotherapy: Treatments at this stage are generally aimed at relieving the patient's symptoms.

Chemotherapy: Systemic chemotherapy aims to control the spread of cancer to other parts of the body.

Targeted Therapies and Immunotherapy: Some patients may receive targeted therapies or immunotherapy, depending on genetic mutations or molecular characteristics of the tumor.

At each stage, the response to treatment and the patient's condition are evaluated regularly. Treatment plans are personalized based on the patient's needs and preferences. Additionally, supportive care and palliative care services may be offered to improve patients' quality of life and manage treatment side effects. Significant advances have been made in the treatment of endometrial cancer in recent years, and new treatment options such as molecular targeted therapies and immunotherapy are being investigated. It is important for patients to have detailed discussions with their doctors about treatment options and possible side effects.

Image 3: Endometrial cancer can cause many complaints such as abnormal vaginal bleeding, abdominal pain and difficulty urinating.

WHAT ARE THE DRUGS USED IN TREATMENT?

There are various chemotherapies, hormonal drugs, targeted (smart) drug treatments and immunotherapies used in the treatment of endometrial cancer. These treatment methods may vary depending on the stage and type of cancer and the patient's general health condition. Some common treatment options used in endometrial cancer:

Chemotherapy Drugs:

Platinum Based Agents: Carboplatin and cisplatin.

Taxanes: Paclitaxel and docetaxel.

Antimetabolites: 5-fluorouracil.

Anthracycline: Doxorubicin.

Hormonal Treatments:

Progesterone Treatments: Medroxyprogesterone acetate and megestrol acetate.

Aromatase Inhibitors: Letrozole, anastrozole and exemestane. (It is especially used in advanced stage or recurrent patients.)

Targeted (Smart) Drug Therapies:

mTOR Inhibitors: For example, Temsirolimus.

Angiogenesis Inhibitors: Bevacizumab.

Immunotherapies:

Programmed Cell Death Protein 1 (PD-1) Inhibitors: Pembrolizumab and Dostarlimab.

These treatment options are often used in combination or alone in the treatment of endometrial cancer and are chosen by considering the potential side effects of each treatment method and the patient's health condition. New treatment options and clinical research in the treatment of endometrial cancer are constantly developing, and it is important for patients to discuss treatment options and possible side effects with their doctors in detail.

HOW SHOULD FOLLOW-UP BE CARRIED OUT AFTER RECOVERY?

Follow-up after recovery from endometrial cancer is vital to monitor the patient's overall health, detect possible recurrences early, and manage treatment side effects. The follow-up process is often customized depending on the patient's response to treatment and overall health. Follow-up usually begins after completion of surgery or other treatments and is more frequent during the first few years. During this period, patients are generally evaluated by a gynecological oncologist every 3-6 months. These evaluations include a pelvic exam, medical history, and review of symptoms. When necessary, blood tests (e.g. CA-125), radiological examinations (e.g. pelvic ultrasound, CT or MRI) and other laboratory tests may also be performed. Patients are encouraged to be informed about their symptoms and to promptly report any new symptoms (e.g., abnormal vaginal bleeding, pelvic pain). Post-treatment follow-up may also include supportive care and rehabilitation services to manage treatment side effects and improve patients' quality of life. Regular follow-up after endometrial cancer treatment plays a critical role in ensuring early diagnosis and appropriate treatment interventions, tailored to each patient's individual needs.