What is Uterus?
Uterus (womb) is a hollow, inverted pear-shaped organ that accommodates the growing fetus during pregnancy. It is situated between the urinary bladder and rectum in the pelvic cavity and it is held in position by several uterine ligaments. It is made-up of mainly 3 tissue layers:
- the outermost, perimetrium (an extension of peritoneum that is composed of areolar connective tissue and forms few uterine ligaments and covers several organs in the pelvis);
- the middle layer, myometrium (composed of smooth muscle fibers that produce powerful coordinating contractions to expel the fetus during labor); and
- the innermost, endometrium (which is the site for endometrial cancer and is further divided into basal and functional layer). The functional layer is transient which develops and shed in cycles in response to mainly two hormones estrogen and progesterone until the menopause (cessation of menstrual cycles in women). The basal layer is permanent and gives rise to a new functional layer after each menstrual cycle.
What are the types of Endometrial Carcinoma?
Endometrioid adenocarcinomas are the most commonly encountered (about 95% of all cases) endometrial cancer. Other less common but aggressive subtypes of endometrial adenocarcinoma include clear-cell carcinoma, mucinous adenocarcinoma, and papillary serous adenocarcinoma. Most endometrial cancers develop from precancerous lesions known as endometrial hyperplasia (an abnormally increased growth of endometrium). Endometrial hyperplasia is divided into four subtypes: simple hyperplasia, complex hyperplasia, simple atypical hyperplasia, and complex atypical hyperplasia. The risk of developing endometrial cancer is highest (about 29%) in complex atypical hyperplasia. All the pre-cancerous lesions are generally treated to avoid a development into invasive disease.
Endometrial Cancer Risk Factors
During the reproductive phase in women, starting from menarche until menopause, ovaries produce estrogen and progesterone that bring about cyclic changes in the endometrium. Any disturbance in the balance between the two hormones (especially a shift towards more estrogen) increases the risk of endometrial cancer. Prolonged exposure to estrogen is the single most important risk factor which is found associated with endometrial cancer.
Early menarche/late menopause
Early starting of menses and delayed age of menopause has been reported to elevate the risk of developing endometrial cancer, by increasing the exposure of endometrium to estrogen hormone. The increased risk is postulated to be related to the longer duration of exposure to the estrogen.
Women who never carried a full-term pregnancy are considered to be at higher risk of developing endometrial cancer probably due to the protective effect of pregnancy that shifts the hormonal level towards more progesterone.
Hormone replacement therapy
Treating menopause symptoms like hot flashes, vaginal dryness, and osteoporosis with hormones especially estrogen alone (without progesterone) may lead to an increased risk of endometrial cancer by about fivefold.
Tamoxifen is used to prevent or treat breast cancer in some patients which acts as an anti-estrogen for breast cells but as a weak estrogen for endometrium. Thus, the use of tamoxifen in breast cancer can increase the risk of developing endometrial cancer.
Women with a history of radiation treatment for the pelvis (maybe for the treatment of other cancer like cervix or colorectal cancer) are at increased risk of developing endometrial cancer.
Certain ovary disorders like polycystic ovarian syndrome (PCOS) and certain ovary tumors can lead to an abnormally high level of estrogen. Such a high level of estrogen increases the risk of developing endometrial cancer.
Overweight or obese women are at higher risk of developing endometrial cancer which may be due to a higher exposure to estrogen that is produced by the fat tissue after menopause.
Risk of developing endometrial cancer increases in females with a history of endometrial cancer in close relatives.
For example (e.g.), Lynch syndrome (or hereditary nonpolyposis colon cancer [HNPCC] caused due mutation in genes: MLH1, MLH3, MSH2, MSH6, TGFBR2, PMS1, and PMS2.
Older age, consumption of a high-fat diet, lack of physical activity and longer sitting hours are other risk factors for endometrial cancer. Hypertension and diabetes may be secondary to obesity but they have been reported to raise the risk of endometrial cancer.
Apart from the above-listed risk factors, certain protective factors which can reduce the risk of endometrial cancer have also been identified. Such protective factors mainly include full-term pregnancy, multiparity (multiple pregnancies), use of an intrauterine device, and oral contraceptives use for birth control.
Endometrial Cancer Symptoms and Signs
Local spread may cause:
- Pressure like sensation in lower abdomen
- Uterine bleeding that is irregular and/or out of proportion to normal
- Painful sexual intercourse
- Vaginal discharge that appears unusual
Distant spread may cause:
- Bone pain, back pain
- Yellowish discoloration of eyes and/or urine
- Chest discomfort, cough, breathlessness
- Abdominal distension and/or discomfort, bloating
Most common sites of spread of uterine cancer are bone, liver, lung, peritoneum and vagina.
Investigations for Staging Endometrial Cancer
Transvaginal Ultrasound (TVUS)
To examine the endometrium, fallopian tubes, ovaries, and other nearby structures for any abnormality. This test can detect any solid tumors (appear as a solid mass) or abnormal endometrial thickening that may indicate endometrial cancer. This test can also provide information regarding the location, extent of disease or invasion into the muscle layer (myometrium).
In this technique, a tiny telescope-like device is inserted into the uterus through the vagina and cervix to closely examine the endometrium. This enables a doctor to determine any abnormal area(s) and to collect biopsy samples from such area(s) observed during the test.
Biopsy sample(s) from the endometrium is generally collected in case an abnormal area(s) is observed during the TVUS or hysteroscopy procedure. This can be removing a small amount of endometrial tissue via a thin tube inserted into the uterus through the cervix.
In case the collected biopsy sample is inadequate or patient is being considered for a fertility-sparing treatment, a dilation and curettage (D&C) can be performed. In D&C, the cervix is dilated and endometrial tissue is scraped from inside of the uterus using special instruments.
One or more of the belowmentioned imaging tests are required to stage the disease and assess response to treatment.
- Computed tomography (CT) scan
- Positron emission tomography (PET) scan
- Magnetic resonance imaging (MRI) scan
Blood tests for tumor markers
Tumor markers are generally proteins or other substances that are produced by both normal cells and cancer cells. However, in the case of cancer, the level of these markers rises in the blood, urine, or other biological fluids, which can be detected by certain laboratory tests. Level of cancer antigen (CA)-125 has been reported to be elevated in many patients with endometrial cancer.
Endometrial Cancer FIGO Staging
Endometrial Cancer FIGO Staging is the most commonly used staging system for the disease. FIGO stands for International Federation of Gynecology and Obstetrics.
FIGO Stage IA
The primary tumor is limited to the endometrium or has invaded less than half of myometrium.
FIGO Stage IB
The primary tumor has invaded half or more of the myometrium.
FIGO Stage II
The primary tumor is present only in the uterus and has extended up to the cervical connective tissue.
FIGO Stage IIIA
The cancer cells have spread to the outer surface of the uterus (serosa) or to the fallopian tube, ovary, round/broad ligament (adnexa).
FIGO Stage IIIB
The cancer cells have spread to the vagina or up to the parametrium.
FIGO Stage IIIC1
Cancer has spread to pelvic lymph nodes but not to the lymph nodes along the aorta or to distant body parts.
FIGO Stage IIIC2
Cancer has spread to the lymph nodes along the aorta but not to the distant body parts.
FIGO Stage IVA
Cancer has spread up to the mucosa of the rectum or urinary bladder.
FIGO Stage IVB
The cancer cells have spread to distant body parts such as distant lymph nodes, lungs, bones, liver, etc.
Endometrial Cancer Treatment
The endometrial cancer treatment depends on various factors including the type of endometrial cancer, stage of the disease, grade of the tumor, patient’s preference (for example, to retain fertility or not), performance status of the patient, along with other factors.
FIGO STAGE I
In case of Stage I endometrial cancer, after hysterectomy, the patient may be kept on observation or may be given radiation therapy with/without chemotherapy depending on stage, grade and other risk factors.
FIGO STAGE II
In case of Stage II endometrial cancer, after hysterectomy, patient requires radiation therapy with/without chemotherapy in most cases.
FIGO STAGE III
In case of Stage III endometrial cancer, surgery (performed only if all cancer tissue can be removed) followed by chemotherapy and/or radiotherapy is considered as the standard treatment.
FIGO STAGE IV
In case of Stage IV endometrial cancer, hormone therapy or chemotherapy is generally considered as the standard treatment. Surgery and or radiotherapy may also be employed alongside hormone therapy or chemotherapy as palliative treatment to relieve symptoms.
Surgery for Endometrial Cancer
Surgery is the first-line treatment for many early-stage and some advanced-stage endometrial cancers. There are mainly 2 aims of surgery in endometrial cancer: first is to stage the disease and second is to remove all possible cancerous tissue to treat the disease.
Hysterectomy is commonly employed for the management of endometrial cancer. In a total hysterectomy, the entire uterus is removed keeping all other structures. In a radical hysterectomy, the uterus along with associated tissues like parametria, uterus ligaments, part of the vagina, pelvic lymph nodes, and fallopian tubes and ovaries are removed.
Role of Hormonal Therapy
This treatment approach is based on the fact that most endometrial cancer cells grow under the influence of estrogen. Estrogen is predominately produced by the ovaries and a small amount is also produced by the fat tissue in females.
Depriving the endometrial cancer cells of the estrogen or by lowering the estrogen level in the blood cause their shrinkage or make them grow very slowly. Following are some common types of hormonal therapy used for the treatment of endometrial cancer:
Progestins: Drugs like medroxyprogesterone acetate and megestrol acetate are commonly used progestins which act similar to progesterone and inhibit estrogen to produce its eliciting effect on endometrial cancer cells.
Tamoxifen: Tamoxifen is a drug commonly used in breast cancer and can be used to treat advanced-stage endometrial cancer. It blocks the estrogen receptors in cancer cells and can act as a weak estrogen in other body tissues like bones.
Luteinizing hormone-releasing hormone agonists: These drugs (e.g. leuprolide, and goserelin) decrease the level of estrogen in the blood by acting on the pituitary gland which in turn signals to stop the production of estrogen from the ovaries. These drugs can be used alone or in combination with other hormonal drugs in pre-menopausal women.
Aromatase inhibitors (AIs): Aromatase is an enzyme that helps in the production of estrogen from fatty tissue. In post-menopausal women, fatty tissue is the main source of estrogen. Thus, AIs (e.g. letrozole, anastrozole, and exemestane) help in lowering estrogen levels in post-menopausal women and used for the treatment of endometrial cancer in such patients.
Role of Chemotherapy
Chemotherapy may be used for endometrial cancer treatment as a part of concurrent chemoradiation (chemotherapy given in combination with radiothrapy), adjuvant chemotherapy (chemotherapy after surgery) or palliative therapy (in patients with metastatic disease).
The chemotherapy drugs that are a part of endometrial cancer treatment regimens are-
- Paclitaxel, Docetaxel
- Carboplatin, Cisplatin
Best Endometrial (Uterine) Cancer Specialist in Delhi
Dr Sunny Garg is a renowned Medical Oncologist in New Delhi with an experience of around 10 years of treating uterine cancer patients. He has treated endometrial cancer patients with Chemotherapy, Targeted Therapy, Hormonal Therapy, and Personalized Cancer Treatment. He is currently practicing at Manipal Hospital, Dwarka.
Diagnostic modalities available at our hospital include Hysteroscopy, Endometrial Biopsy, CT Guided Biopsy, Transvaginal Ultrasound, Whole Body PET CT, etc. Other treatment facilities for Endometrial Cancer available are Radical Hysterectomy, Radiation Therapy, etc.
Call +91 9686813020 for appointment.