Uterine adenocarcinoma develops from the secretory epithelium lining the mucous membrane of the uterus (womb). This type of uterine cancer is among the most common malignant tumors of the female reproductive system. Endometrial adenocarcinoma ranks third among oncological diseases in women. Approximately 80-90% of patients with womb (uterus) cancer are diagnosed with endometrial cancer.

Etiology

The main factors contributing to the development of endometrial cancer include:

• Hyperestrogenism (increased blood estrogen levels).
• Early onset of menstruation.
• Age over 55 years.
• Nulliparity (absence of childbirth).
• Late onset of menopause.
• Use of specific medications, such as tamoxifen.

Genetic factors contribute only about 5% to the development of uterine cancer, meaning it is rarely hereditary. Endometrial adenocarcinoma is infrequently diagnosed in close female relatives. However, Lynch syndrome, a genetic condition, is an exception. It involves a combined risk of developing tumors in the uterus, ovaries, colon, brain, and pancreas.

Classification

Endometrial adenocarcinoma can be categorized based on various characteristics. Proper classification is critical for determining treatment strategies and predicting outcomes.

Based on Growth Pattern:

• Exophytic adenocarcinoma: The tumor grows into the uterine cavity.
• Endophytic adenocarcinoma: The tumor grows beyond the uterus, invading surrounding tissues.

Based on Cellular Structure:

• Mucinous adenocarcinoma.
• Serous adenocarcinoma.
• Mixed adenocarcinoma.
• Endometrioid adenocarcinoma.

Based on Degree of Differentiation:

• Well-differentiated (G1).
• Moderately differentiated (G2).
• Poorly differentiated (G3).

The degree of differentiation reflects the tumor’s malignancy. Tumors with higher differentiation (G1) resemble normal cells and are less aggressive. Conversely, poorly differentiated tumors (G3) show significant cellular atypia and are more aggressive.

Types of endometrial cancer

Endometrial cancer can be categorized into two pathogenetic types:

1. Estrogen-sensitive tumors (Type 1):
   These are commonly found in postmenopausal women and patients with obesity or a history of ovarian, breast, or intestinal cancers. Most tumors in this category are highly differentiated.
2. Non-estrogen-sensitive tumors (Type 2):
   These are less common and are characterized by deeper invasion into the myometrium. They are typically low-differentiated and have a higher propensity for lymphatic metastasis.

Additionally, based on the differentiation grade of tumor cells, endometrial adenocarcinomas can be classified into:

Differentiation Grade	Characteristics
Highly differentiated (G1):	Found in no more than 5% of cases; most cells retain a normal structure, and the tumor grows slowly.
Moderately differentiated (G2):	Found in 5–50% of cases; heterogeneous cells are observed, with increased cell division.
Low-differentiated (G3):	Found in more than 50% of cases; marked cellular polymorphism and pathological changes in cell structure; aggressive growth.

Stages of uterine cancer

The stage of uterine cancer, specifically endometrial adenocarcinoma, is determined using the standard TNM system or the International Federation of Gynecology and Obstetrics (FIGO) classification. Both systems account for the growth characteristics and size of the primary tumor, involvement of regional lymph nodes, and the presence of distant metastases.

There are four stages of uterine cancer. Accurate staging is critical for selecting the appropriate treatment approach. Therefore, all patients suspected of having uterine tumors undergo comprehensive diagnostics to establish an accurate diagnosis.

Cancer progression by stage

The stages of uterine cancer are classified as follows:

1. Stage I:
   The tumor is confined to the uterus:
   • Stage IA: Tumor within the endometrium or invading less than half the myometrial thickness.
   • Stage IB: Cancer invading half or more of the myometrial thickness.
2. Stage II:
   The tumor extends to the cervix:
   • Stage IIA: Cancer localized to the cervical canal.
   • Stage IIB: Uterine cancer invades the cervical stroma.
3. Stage III:
   The tumor spreads beyond the uterus:
   • Stage IIIA: Involves the adnexa (ovaries or fallopian tubes).
   • Stage IIIB: Metastases to the vagina.
   • Stage IIIC: Involvement of pelvic or lumbar lymph nodes.
4. Stage IV:
   The endometrial cancer extends beyond the pelvic cavity:
   • Stage IVA: Invades the rectum or bladder.
   • Stage IVB: Distant metastases are present.

Symptoms

The primary symptoms of endometrial cancer include menstrual cycle disruptions and abnormal uterine bleeding. Women of reproductive age may experience heavier, prolonged menstrual bleeding or irregular cycles with unpredictable durations and intervals. During menopause, vaginal bleeding may occur cyclically or non-cyclically.

In some cases, especially during the early stages, endometrial cancer may present with no noticeable symptoms.

Advanced stages or large tumors with metastases can lead to pronounced clinical signs, such as severe lower abdominal pain, urinary or bowel disturbances, leg swelling, and other symptoms.

Early-stage endometrial cancer may be asymptomatic and is often discovered incidentally during routine or unrelated examinations. However, most patients seek medical attention when experiencing alarming symptoms, such as abnormal uterine bleeding.

Symptoms include:

• Premenopausal women:
  Heavy and prolonged menstruation, intermenstrual bleeding, and watery discharges with an unpleasant odor.
• Postmenopausal women:
  Uterine bleeding after menopause.
• Advanced stages:
  • Lower abdominal pain.
  • Discomfort or pain during intercourse (dyspareunia).
  • Weakness, appetite loss, and unexplained weight loss.
  • Fever.
  • Bowel and bladder dysfunction when the tumor invades these organs.

Large endometrial tumors can compress or metastasize to adjacent organs such as the rectum and bladder, leading to urinary and bowel issues accompanied by pain. Metastases in lymph nodes may result in their enlargement and, in some cases, unilateral lower limb swelling due to impaired lymphatic drainage.

Note: As with other cancers, early detection of uterine cancer significantly improves treatment outcomes. Therefore, women experiencing abnormal symptoms should seek medical evaluation promptly.

Endometrial cancer diagnosis

The diagnostic plan for endometrial cancer is always individualized and determined only after consulting a doctor. It may include the following methods:

• Standard gynecological examination on a chair.
• General clinical tests (complete blood count, biochemical blood test, general urine analysis, coagulogram).
• Imaging of the pelvic organs, abdominal cavity, and retroperitoneal region through ultrasound examination.
• Separate diagnostic curettage.
• Aspiration biopsy.
• Determination of tumor markers in the blood.
• Colposcopy.
• Excretory urography.
• Cystoscopy.
• MRI of internal organs.
• Molecular-genetic studies.
• CT, PET-CT, and others.

Endometrial (womb) cancer treatment

As with many other malignant tumors, surgical treatment of endometrial cancer plays the primary role and involves removing the tumor.

First stage

If uterine cancer (endometrial adenocarcinoma) is detected at the first stage, a hysterectomy is performed. This surgery entails the removal of the entire uterus (including the cervix), fallopian tubes, ovaries, the upper third of the vagina, and adjacent lymph nodes along with fatty tissue. In some cases, removal of the omentum and pelvic and lumbar lymph nodes is indicated. After surgery, peritoneal washes are analyzed to detect tumor cells and assess the spread of the malignancy.

In certain situations, surgery is combined with chemotherapy during the postoperative period.

Second stage

For second-stage endometrial cancer, treatment follows a similar approach, but radiation therapy is mandatorily administered after surgery, sometimes in combination with chemotherapy.

Third stage

If womb (uterus) cancer is diagnosed at the third stage, treatment begins with radiation therapy. This can involve either intracavitary radiation (where a probe is inserted into the uterine cavity) or external radiation (with the machine positioned at a distance from the patient). The duration of radiation therapy is customized based on the tumor’s size and cellular structure. The second stage involves radical surgery, followed by chemotherapy or additional radiation therapy. Often, alternating courses of chemo- and radiotherapy are employed, as this approach is considered the most effective.

Fourth stage

At the fourth stage of endometrial cancer, only palliative treatment is possible. Different surgical interventions may be performed. For instance, if the tumor invades the rectum or bladder, a complete removal of pelvic organs (exenteration) may be carried out. This surgery is only feasible if there are no metastases in the pelvic fat tissue and the patient’s general health is satisfactory. If this is not possible, other interventions aimed at maximum tumor tissue removal are performed. Treatment options may also include the application of chemotherapy and radiation therapy.

Palliative treatment is aimed at reducing symptom severity and improving the patient’s quality of life.

Surgical treatment

The scope of surgical intervention depends on the cancer stage, which is determined during the preoperative examination:

1. First Stage: Extrafascial removal of the uterus and appendages, pelvic and para-aortic lymphadenectomy, along with the removal of fatty tissue.
2. Second Stage: Extended extrafascial extirpation of the uterus with appendages, removal of the upper part of the vagina, combined with iliac-pelvic and lumbar lymphadenectomy, followed by adjuvant chemotherapy.
3. Third Stage: Surgery in combination with pelvic and lumbar lymph node dissection in the first stage, followed by adjuvant chemotherapy.

Medical supervision after treatment

After treatment for endometrial adenocarcinoma, regular medical follow-up is essential regardless of the stage of uterine cancer. For the first three years, the patient should undergo gynecological examinations every three months, including cytology tests to detect cancer cells.

Over the next two years, these examinations should be performed every six months, and subsequently, once a year.

Additionally, an annual chest X-ray is conducted to rule out the presence of metastases. It is also recommended to examine the breasts at least once a year.

For patients with previously elevated levels of the tumor marker CA-125, monitoring its levels during follow-up visits is crucial. This analysis should be performed at every doctor’s appointment. An increase in CA-125 levels could indicate a recurrence of endometrial cancer. If complaints arise, additional diagnostic methods such as pelvic ultrasound or abdominal MRI may be prescribed.

Effectiveness of treatment

The success of treating any malignancy, including endometrial cancer, relies heavily on how quickly the disease is detected. To minimize potential risks, it is essential to undergo routine gynecological examinations and necessary tests.

Prompt medical attention should be sought if any symptoms of the genitourinary system arise. Special attention is warranted for women with a family history of cancer or other risk factors for malignancies of the reproductive system.

What prognosis does it have?

The prognosis for womb (uterus) cancer depends on the stage of the endometrial adenocarcinoma. Early detection and timely treatment significantly reduce the risk of recurrence. However, the prognosis becomes less favorable at more advanced stages.

Other factors influencing the prognosis include:

• Low differentiation of tumor cells.
• Extensive involvement of the uterus (over half of its volume).
• Large tumor size.
• Low levels of estrogen or progesterone receptors.
• Patient age over 60 years.
• Chromosomal abnormalities in tumor cells.
• Spread of the cancer to the cervical tissue.

Given the strong correlation between the disease stage and prognosis, regular gynecological check-ups are critical. At the first signs of reproductive system dysfunction, patients should seek immediate medical evaluation. Early diagnosis and treatment of endometrial cancer can significantly improve outcomes.

Endometrial cancer survival rates

Survival rates after surgical treatment of endometrial adenocarcinoma depend on several factors, primarily the timely initiation of therapy. Additionally, the degree of tumor differentiation affects the prognosis. High-grade tumors have better outcomes compared to low-grade ones. Age also plays a role, with younger women having higher survival rates than those over 70 years of age.

According to data from the International Federation of Gynecology and Obstetrics (FIGO), the average five-year survival rates are as follows:

• Stage 1: 80% of patients.
• Stage 2: Approximately 70%.
• Stage 3: Complete recovery is possible in 41% of cases.
• Stage 4: Recovery is feasible in no more than 9% of patients.

References:

• Oaknin A., Bosse T.J., Creutzberg C.L., et al. “Endometrial cancer: ESMO Clinical Practice Guideline for diagnosis, treatment, and follow-up.” DOI: https://doi.org/10.1016/j.annonc.2022.05.009
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• Ryzhavsky B.Ya., Shapiro E.P., et al. “Morphometric Characteristics of Tumor Cells in Endometrial Adenocarcinoma.” Far Eastern Medical Journal, 2005.
• Sargsyan S.A., Kuznetsov V.V., et al. “Cervical Adenocarcinoma.” Russian Journal of Oncology, 2006.
• Münstedt K., Grant P., et al. “Cancer of the Endometrium: Diagnostics and Treatment.” World J Surg Oncol, 2004.
• MacKay H.J., Rodriguez Freixinos V., Fleming G.F. “Therapeutic Targets and Opportunities in Endometrial Cancer.” ASCO Educational Book, 2020.
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