Endometrial Cancer

The cancer that can be detected early.

Uterine cancer is the most common gynecological cancer. It is usually diagnosed early and successfully treated. 95% of endometrial cancers develop from the uterine wall, and include uterine carcinomas and adenocarcinomas.

Factors that might increase the risk of endometrial cancer include:

Age – As with most cancers, the risk of developing endometrial cancer increases with age.
Obesity and Lack of Physical Activity – Obesity is a significant risk factor, as fat tissue produces estrogen, a hormone that can increase the risk of endometrial cancer. About 70% of endometrial cancer cases are linked to obesity, and this type of cancer is twice as common among overweight women.
Hormonal Factors – A hormone imbalance where estrogen levels exceed progesterone levels can raise the risk of endometrial cancer.

Warning Signs?

If you experience one of the following symptoms of endometrial cancer, consult a healthcare provider.

Abnormal vaginal bleeding
Excessive menstrual bleeding
Postmenopausal vaginal bleeding
Pelvic pain
Abnormal vaginal discharge
Unintentional weight loss
Palpable pelvic mass
Disruption of bladder function (urinary retention or incontinence)

Diagnosis

The diagnosis is typically made following suspicious symptoms and is based on physical and gynecological exams, biopsies performed via pipelle or hysteroscopy, imaging of the pelvis and abdomen (ultrasound, CT, or PET-CT), and blood tests including liver and kidney function and CA-125 protein levels.

What is the Uterus?

The uterus is a muscular organ located at the top of the cervix, where the fetus develops during pregnancy.

The uterus is composed of three layers:

Endometrium – The inner lining
Myometrium – The thickest layer, comprising mostly muscle
Serosa – The thin outer layer

During a woman’s reproductive years, if pregnancy does not occur, the endometrial lining is shed through the vagina (menstruation). This process continues until menopause, when the ovaries stop releasing eggs, and the endometrium becomes thin and inactive.

The uterus is supported by the pelvic floor muscles.

Uterine Cancer

Endometrial cancer is often detected early and is usually fully curable. Early detection, along with significant advances in available treatment options, offers real hope to patients. Awareness and consistent and regular gynecological check-ups are key to early diagnosis, improving the chances of recovery and successful treatment.

Types of Uterine Tumors:

Adenocarcinoma: This tumor originates in the inner lining of the uterus (endometrium) and is known as endometrial adenocarcinoma. It is usually diagnosed at an early stage and has high cure rates. The most common subtype is endometrioid carcinoma. Less common subtypes include serous carcinoma, the rare clear cell adenocarcinoma, and carcinosarcoma, which is a mix of adenocarcinoma and sarcoma.

Uterine Sarcoma: This type of cancer develops in the supporting tissues of the uterine glands or in the myometrium, the muscular layer of the uterus, rather than in the endometrium. Uterine sarcomas account for about 2% to 4% of uterine cancer cases. Subtypes include leiomyosarcoma (the most common subtype), endometrial stromal sarcoma, and undifferentiated sarcoma.

Staging of Endometrial Cancer

Treatment for endometrial cancer is determined based on the stage of the disease. In 2022, the International Federation of Gynecology and Obstetrics (FIGO) updated the staging system for endometrial cancer. The staging system classifies the size and spread of the cancer, helping doctors decide on the appropriate treatment and its duration. The major updates include incorporating risk stratification, histological features, growth patterns, and even molecular classifications. Below is the updated staging system for endometrial cancer:

Stage I - Confined to the uterine corpus and ovary

IA: Disease limited to the endometrium OR non-aggressive histological* type, i.e. low-grade endometroid, with invasion of less than half of myometrium with no or focal lymphovascular space involvement (LVSI) OR good prognosis disease
IA1: Non-aggressive histological type limited to an endometrial polyp OR confined to the endometrium
IA2: Non-aggressive histological types involving less than half of the myometrium with no or focal LVSI
IA3: Low-grade endometrioid carcinomas limited to the uterus and ovary

IB: Non-aggressive histological types with invasion of half or more of the myometrium, and with no or focal LVSI

IC: Aggressive histological types limited to a polyp or confined to the endometrium

Stage II - Invasion of cervical stroma without extrauterine extension OR with substantial LVSI OR aggressive histological types with myometrial invasion

IIA: Invasion of the cervical stroma of non-aggressive histological types

IIB: Substantial LVSI of non-aggressive histological types

IIC: Aggressive histological types with any myometrial involvement

Stage III - Local and/or regional spread of the tumor of any histological subtype

IIIA: Invasion of uterine serosa, adnexa, or both by direct extension or metastasis
IIIA1: Spread to ovary or fallopian tube (except when meeting stage IA3 criteria)
IIIA2: Involvement of uterine subserosa or spread through the uterine serosa

IIIB: Metastasis or direct spread to the vagina and/or to the parametria or pelvic peritoneum
IIIB1: Metastasis or direct spread to the vagina and/or the parametria
IIIB2: Metastasis to the pelvic peritoneum

IIIC: Metastasis to the pelvic or para-aortic lymph nodes or both
IIIC1: Metastasis to the pelvic lymph nodes
IIIC1i: Micrometastasis
IIIC1ii: Macrometastasis
IIIC2: Metastasis to para-aortic lymph nodes up to the renal vessels, with or without metastasis to the pelvic lymph nodes
IIIC2i: Micrometastasis
IIIC2ii: Macrometastasis

Stage IV - Spread to the bladder mucosa and/or intestinal mucosa and/or distance metastasis

IVA: Invasion of the bladder mucosa and/or the intestinal/bowel mucosa

IVB: Abdominal peritoneal metastasis beyond the pelvis

IVC: Distant metastasis, including metastasis to any extra- or intra-abdominal lymph nodes above the renal vessels, lungs, liver, brain, or bone

* Histology is the scientific field that studies the structure of living tissues. It involves identifying, examining under a microscope, and analyzing these tissues. Histology is essential in medicine as it allows doctors to diagnose diseases and monitor treatments. Additionally, histology plays a crucial role in scientific research, helping to understand the structure and function of tissues.

Treatment for Endometrial Cancer

Surgery – In most cases, the disease can be cured with surgery aimed at removing the tumor. Typically, this involves a hysterectomy (removal of the uterus), and sometimes also the removal of the fallopian tubes and ovaries. Read more about surgeries here.

Radiation Therapy – Sometimes radiation is necessary, either as external radiation or vaginal brachytherapy. Read more about radiation therapy here.

Chemotherapy – During surgery, biopsy samples are taken from lymph nodes to determine the stage of the disease. If the tumor has spread to the lymph nodes or if the tumor’s histology is unique, chemotherapy may be included in the treatment plan to destroy cancer cells. Chemotherapy typically involves a combination of drugs. Platinum salts and taxanes, long proven to be effective in treating uterine tumors, are the primary components. Read more about chemotherapy here.

For advanced uterine cancer, the standard treatment includes surgery followed by a combination of two chemotherapy drugs (Carboplatin and Taxol) administered in six cycles.

After chemotherapy, a clinical evaluation of the disease is performed. If no signs of the disease are present, the patient is monitored every three months for the first two years and then at increasing intervals.

However, recurrence can happen during or after chemotherapy. In such cases, additional chemotherapy or immunotherapy might be necessary. Over the past few decades, several drugs have been developed for subsequent lines of treatment.

Innovation in Endometrial Cancer

Immunotherapy

Patients with metastatic or recurrent endometrial cancer whose tumors are MSI-H (microsatellite instability-high) or dMMR (deficient mismatch repair) are eligible for immunotherapy. This treatment is available through the “healthcare basket” as a second-line option, meaning it is offered after chemotherapy for those needing continued treatment.

Patients whose tumors are pMMR (proficient mismatch repair) may receive immunotherapy in combination with targeted therapy, specifically with tyrosine kinase inhibitors (TKIs).

Targeted Therapy

Tyrosine kinase inhibitors (TKIs) work through two main mechanisms to block cancer cell growth while minimizing damage to healthy cells. These include disrupting a protein that promotes cancer cell division, thereby slowing tumor growth, and blocking the VEGF receptor, which is responsible for supplying blood to the cancer cells, cutting off the tumor’s nutrient source.

Biological Therapy

Another commonly used drug is Avastin, an anti-angiogenesis medication. It is an antibody that blocks the formation of new blood vessels around the tumor. Cancerous tumors rely on recruiting new blood vessels to ensure a continued supply of oxygen and nutrients for their growth.

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Endometrial Cancer