Endometrioid Adenocarcinoma - Causes and Prevention

What Is Endometrioid Adenocarcinoma and How Is It Treated?

Endometrioid adenocarcinoma is the most common type of endometrial cancer. It makes up about 75 to 80% of all cancers that affect the uterus. This cancer starts in the gland-like cells that line the uterus. These cells are called endometrial cells. It is also known as type 1 endometrial cancer.

Endometrioid adenocarcinoma usually develops when there is too much estrogen in the body and not enough progesterone to balance it. In many cases, this cancer is found early. Early diagnosis can improve the chances of successful treatment. Compared to the rarer types of endometrial cancer, the outlook is generally better.

How Is Endometrioid Adenocarcinoma Different From Other Uterine Cancers?

There are two main types of endometrial cancer.

• The first type grows slowly. It is linked to hormones and is often found at an early stage.

• The second type includes rare cancers like serous adenocarcinoma, clear cell carcinoma, and carcinosarcoma. These cancers are usually more aggressive.

Doctors treat these two types differently. The follow-up care, monitoring, and additional treatments can also vary. A person with endometrioid adenocarcinoma has a different condition from someone with uterine serous carcinoma. Even though both are called uterine cancer, they are not the same disease. Endometrioid adenocarcinoma is connected to several risk factors. Because of this, some cases may be partly preventable.

What Causes Endometrioid Adenocarcinoma?

The main cause is too much estrogen without enough progesterone to balance it. Over time, this hormone imbalance causes the uterine lining to become thicker than normal. At first, this may lead to endometrial hyperplasia. In some cases, it can progress to atypical hyperplasia. Later, it may develop into adenocarcinoma. Several factors may increase the risk of developing this condition.

These include:

• Obesity: Excess weight leads to increased estrogen levels by converting androgens into estrogens independent of ovarian function. This factor ranks high among modifiable risks.

• Poly-Metabolic Ovary Syndrome / Polycystic Ovarian Follicular Syndrome: Chronic anovulation implies a lack of progesterone and constant exposure of the endometrium to unopposed estrogen.

• Unopposed Estrogen Therapy: Hormone replacement therapy using only estrogen increases the chances of endometrial cancer when used for an extended period of time.

• Tamoxifen Use: Tamoxifen (treatment for breast cancer) acts as an estrogen agonist on the endometrium.

• Diabetes and Insulin Resistance: Hyperinsulinemia (elevated insulin) stimulates ovarian androgen production and raises free estrogen levels.

• Lynch Syndrome: An inherited DNA mismatch repair disorder that significantly elevates the lifetime risk of endometrial cancer.

Women who have never given birth may have a higher risk of this condition. The risk is also higher in women with a family history of endometrial cancer or colorectal cancer. Women who were previously diagnosed with atypical endometrial hyperplasia are also at increased risk.

Our Patients Recently Asked:

Why Did My Endometrial Hyperplasia with Atypia Become Cancer?

Hyperplasia is considered a pre-cancerous condition. In this condition, the cells in the lining of the uterus grow abnormally. However, the abnormal cells do not spread to nearby tissues. If left untreated, around 20% to 30% of cases may turn into endometrioid adenocarcinoma.

What Are the Symptoms?

Abnormal vaginal bleeding is the most common symptom of this cancer. This is also the reason why many cases are detected early. Any bleeding after menopause is not normal and should be checked by a doctor.

Before menopause, the following symptoms also need medical attention:

• Heavy menstrual bleeding.

• Bleeding between periods.

• Bleeding that happens at unusual times.

Other symptoms that may occur include:

• Watery or blood-stained vaginal discharge.

• Pain or pressure in the lower abdomen or pelvic area.

• Pain during sexual intercourse.

• Unexplained weight loss in later stages.

Early bleeding is actually an important warning sign for this cancer. Around 80% of endometrial cancers are diagnosed early because women notice abnormal bleeding and seek medical help. In many advanced cases, the bleeding symptoms are ignored for months or are mistaken for perimenopause changes. This delay can lead to a later-stage diagnosis.

How Is It Diagnosed?

Diagnosis requires tissue sampling. Imaging can raise suspicion but cannot confirm endometrioid adenocarcinoma.

• Transvaginal Ultrasound: Measures endometrial thickness. A thickened endometrial lining in a postmenopausal woman, usually greater than four to five millimeters, is indicative of the need for biopsy.

• Endometrial Biopsy: A procedure done in the office whereby a sample of tissue from the lining of the uterus is taken for pathological review. This is the gold standard initial diagnostic procedure.

• Hysteroscopy with Biopsy: Visualization of the uterine cavity using an internal viewing device in conjunction with sampling. This test is ordered if the office biopsy fails to give a conclusive result or in cases of focal lesions within the uterine cavity.

• Magnetic Resonance Imaging: An imaging procedure done after diagnosis to determine how far the tumor has invaded the myometrium (depth of myometrial invasion) and the cervical involvement (both are used to stage the disease).

The pathology results from the biopsy will indicate the histology of the tumor (endometrioid or non-endometrioid), its grade, and whether there is any lymphovascular space invasion by cancer cells.

Grading and What It Means

The endometrioid adenocarcinomas can be classified as grades 1, 2, or 3 depending on the proportion of the tumor made up of solid elements rather than glandular structures. The greater the degree of abnormality in the cell structure, the higher the grade and aggression.

How Is Endometrioid Adenocarcinoma Treated?

The treatment of choice will depend upon the stage at which the cancer has been diagnosed, the grade of the tumor, the depth of the penetration of cancer into the uterus, and the general health of the patient. Surgery is often the first line of treatment.

Surgery:

The treatment consists of performing a hysterectomy as well as removing the ovaries and the fallopian tubes. Physicians may sometimes examine the nearby lymph nodes. Today, many hospitals perform the surgery through minimally invasive surgery methods such as laparoscopy or robotic surgery. These methods usually help in faster recovery. For younger women with early-stage and low-grade cancer who want to preserve fertility, high-dose hormone therapy may be an option. This treatment needs close monitoring and repeated biopsies.

Radiation Therapy:

The need for radiotherapy will be determined according to the results of the pathology report, which will include high-risk findings such as:

• Deep penetration into the muscle layer of the uterus.

• Invasion of cancer cells into the lymphatic or bloodstream system.

• Spread to the cervix.

• Positive lymph nodes.

Women who have a low risk or are in an early stage of cancer may not require any radiation treatment. Vaginal brachytherapy treatment is mostly performed at the top end of the vagina after surgery, when there is a high risk of cancer, and external radiation is performed.

Chemotherapy and Targeted Therapy:

In the case of early and low-grade cancers, chemotherapy would not be recommended. In the case of grade 3 cancer, chemotherapy could be used for advanced or aggressive cancers. The two chemotherapy drugs used in the procedure include carboplatin and paclitaxel. In high-risk or recurrent cancers, targeted therapy using Pembrolizumab and Lenvatinib could be administered after analyzing the tumor.

Prognosis:

The prognosis will often be good if the cancer is caught early. It all depends on the stage and grade of the cancer. Bowel or bladder complications could arise after radiation therapy. The cancer usually recurs between two and three years post-treatment. Follow-up visits will be very important. Doctors could recommend pelvic examinations, cancer antigen 125 blood tests, and imaging studies.

Conclusion

Endometrioid adenocarcinoma is the most common type of uterine cancer. In many cases, it is also one of the most treatable types. Early abnormal bleeding often acts as a warning sign. This helps doctors diagnose the cancer at an earlier stage. Doctors also understand the hormonal causes of this cancer quite well. The grading system further helps in predicting how the cancer may behave. The stage and grade of the cancer together decide how strong the treatment needs to be. After diagnosis, one of the most important discussions is understanding the exact stage and grade of the cancer and what treatment plan is needed. For a second opinion on an endometrioid adenocarcinoma diagnosis, pathology report, or treatment plan, consult a cancer specialist.

Key Takeaways

• Endometroid adenocarcinoma is the commonest form of uterine cancer. It actually forms 75% to 80% of total cancer in the uterus. It is usually driven by estrogen and is easily detected during the initial stages.

• Grade and stage together determine prognosis. Five-year survival at stage I ranges from 94% at grade 1 to 79% at grade 3.

• Total hysterectomy with bilateral salpingo-oophorectomy and lymph node assessment is the standard first treatment.

• Radiation and chemotherapy after surgery depend on risk factors in the surgical pathology report, not just the biopsy grade.

• Most recurrences happen within the first two to three years, so regular check-ups every three to six months for two years are standard post-treatment.