Overview

Uterine Cancer or cancer of the uterus is a serious condition that affects millions of women worldwide. Older women and those who have crossed menopause are at more risk. In this article, we will discuss the types of uterine cancer, and other aspects of this condition.

Introduction

The uterus, also called the womb, is a large, pear-shaped, hollow organ in the abdomen of women, where the fertilized egg develops into a foetus and then ‘baby’, all through the term of pregnancy. It is made up of an outer envelope of muscles called myometrium and an inner lining of soft tissue called endometrium. At the lower end of the uterus is the cervix which connects the uterus to the vagina. During childbirth, the cervix opens wide, to let the baby slide out of the uterus, into the vagina, and then outside of the body.

The endometrium undergoes changes during every menstrual cycle. In the likelihood of pregnancy, the endometrium starts thickening, and this is spurred by the production of hormones – oestrogen and progesterone. In case there is no conception, the extra layers of endometrium are shed away. This is what happens during every period(s).

Cancer, as we all know, is an abnormal growth of tissue in one or more parts of the body. This happens when DNA, which is responsible for regulating the growth, multiplication and division of cells, undergo one or more mutations that cause rapid, uncontrollable and abnormal growth or division of cells. This can happen in any part of the body, and when the same happens in the uterus, the condition is called uterine cancer.

Types of Uterine Cancer 

Pathological types 

Uterine cancer is an umbrella term for 2 types of cancer actually.

• Endometrial cancer, or Adenocarcinoma of the endometrium: this constitutes 95% of the cases. As the name implies, this develops in the endometrium.
• Uterine sarcoma: this constitutes 5% of the cases and develops in the myometrium.

Since uterine sarcoma is relatively rarer, most people use the terms uterine cancer and endometrial cancer to mean one and the same. Another reason for this, is that the risk factors and symptoms for both types, are quite similar.

Based on location 

 Type 1 endometrial cancers: These are considered less aggressive, which means they do not spread quickly to other tissues, in most cases.

Type 2 endometrial cancers: These are considered more aggressive. They are highly likely to spread to tissues or organs outside the uterus.

Based on spread 

• Stage I cancer: This is limited to the uterus
• Stage II cancer: This has just now spread to the cervix
• Stage III cancer: This has spread to the ovaries, vagina and lymph nodes in the vicinity
• Stage IV cancer: This has spread to the bladder, kidneys, intestines or any other organ in the abdomen

Molecular classification of endometrial cancers has revolutionized the approach to treatment. Here’s an overview:

Molecular Classification 

Endometrial cancers are classified into four molecular subtypes:

1. POLE (Polymerase Epsilon) ultra mutated: Characterized by high mutation rates and excellent prognosis.
2. Microsatellite instability (MSI) high: Associated with defects in DNA mismatch repair genes and a good prognosis.
3. Copy number low: Characterized by low genomic instability and an intermediate prognosis.
4. Copy number high (serous-like): Associated with high genomic instability and a poor prognosis.

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Risk Factors 

Age, lifestyle and family related 

• Age: Women over 50 years of age are at more risk, as in most cases, they have crossed menopause
• Diet high in fat: A high-fat diet that can come from consuming red meats or other sources of fat increases the risk
• Genetic: Women suffering from hereditary nonpolyposis colorectal cancer (HNPCC), also called Lynch syndrome, are at higher risk of developing endometrial cancer than people who do not have this condition

Hormones related 

Any condition that causes higher levels of oestrogen and lower levels of progesterone simultaneously, increases the risk.

• Irregular ovulation: Women suffering from diabetes and polycystic ovarian syndrome (PCOS) have irregular ovulation. This causes higher oestrogen levels and lower progesterone levels in the uterus, thereby increasing the risk.
• Obesity: Excess body fat causes some of the hormones in the body to transform into oestrogen, thereby increasing the risk. Higher the weight, higher the risk.
• Ovarian diseases: Certain types of ovarian tumours increase oestrogen levels and decrease progesterone levels, which ups the risk.
• Hormone therapy: Post menopause, some women go in for hormone therapy. If the same involves higher oestrogen and lower progesterone levels, there is a risk.

Menstrual and reproductive history related  

• Early menarche: If the girl had her menarche before the age of 12 years, her risk of developing uterine cancer in her adult life increases. This is because the uterus is exposed to oestrogen for longer duration.
• Late menopause: In the same way, if menopause happens after 50 years of age, the uterus is again exposed to oestrogen for more years, increasing the risk.
• A combination of the above 2 factors
• Not conceiving: Women who do not get pregnant either by desire or unable to, are at higher risk.

Previous treatments for other conditions

• Cancers in the pelvis: Cancers in the pelvic area would require radiation therapy as part of the treatment. This can damage cell DNA and eventually trigger uterine cancer.
• Estrogen replacement therapy (ERT): ERT given in order to relieve some of the menopause symptoms, without accompanying progesterone, increases the risk.
• Breast cancer treatment: One of the drugs used to treat the condition is tamoxifen. This mimics oestrogen’s role in the uterus and increases the risk.

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Symptoms 

Bleeding and Periods

• In pre-menopausal women: vaginal bleeding in between 2 periods
• In post-menopausal women: Spotting (slight vaginal bleeding which causes blood-stains on clothes)
• Clear, thin, white, watery discharge from vagina which does not have blood in it, and has a foul smell
• Back-to-back periods without any break
• Prolonged, heavy and regular bleeding from vagina in women older than 40

Pain 

• Pain or cramps in the pelvic area
• Painful intercourse
• Pain in the abdomen

Urination 

• Frequent urination
• Pain while urinating

Others 

• Unexplained weight-loss
• A growth or lump in the vagina
• Feeling heavy or full all the time

Diagnosis 

• Pelvic exam: In this, the doctor will first examine the outer part of the genitals or vulva. Then she will insert 2 of her fingers into the vagina while simultaneously pressing the abdomen slightly. This will help her feel the ovaries and vagina. She may also insert a tool called speculum into the vagina. This helps open up the cervix so that she can view both the uterus and cervix for abnormalities.
• Blood test: Also called CA-125 assay, this measures the levels of a protein called CA-125 in the body. This protein acts as one of the markers for cancer.
• Imaging tests: This includes a CT scan, an MRI scan and a transvaginal ultrasound. All these tests help create an image of the uterus on a computer screen.
• Biopsy to be taken with IHC/molecular analysis, the reports come within 1-2 weeks.

Other tests:  

• Endometrial biopsy: As the name implies, a small sample of endometrial tissue is extracted using a thin scope that is inserted through the cervix. The sample is then sent to the lab to be examined under a microscope.
• Hysteroscopy: A long, thin, scope with a light and camera at its end is inserted into the vagina, through the cervix and finally into the uterus. The camera relays the recording which is displayed on a screen. By looking at the screen, the gynaecologic oncologist can choose to move the scope and examine the uterus thoroughly.
• Dilation and curettage (D&C): Similar to an endometrial biopsy as it aims to remove a sample of tissue for examination. An instrument is used to first dilate the cervix and then a scope with curetting or scraping tools attached to the tip is inserted into the uterus. The scraped-up sample is then retrieved and examined in a lab.
• Advanced genome testing: A sample of tumour tissue retrieved using any of the above methods is examined, and the DNA mutations noted down. This helps understand the cause of the cancer and how it can behave with time.

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Treatment options

Treatment Approaches 

Treatment strategies are tailored based on the molecular subtype:

1. POLE ultra-mutated: Observation or minimal treatment due to excellent prognosis.
2. MSI high: Immunotherapy, such as pembrolizumab, has shown promising results.
3. Copy number low: Standard treatment approaches, including surgery, radiation, and hormone therapy.
4. Copy number high (serous-like): Aggressive treatment approaches, including chemotherapy, radiation, and targeted therapies.

Non-surgical options 

• Chemotherapy: This uses powerful medication that can destroy cancerous cells
• Radiation therapy: This uses different types of rays to destroy cancerous cells
• Hormone therapy: Specific hormones are given that can either block the growth of cancer cells, or destroy them
• Immunotherapy: These are drugs which help boost the immune system which will then destroy the cancerous cells
• Targeted therapy: These drugs target specific behaviours in the cancer cells that make them grow or multiply, thereby stopping their growth.

Surgery 

Depending on the stage of the cancer, surgery may be the very first or the very last option to treat uterine cancer. The procedure is called a hysterectomy as it uses a special endoscope called hysteroscope fitted with surgical instruments at the tip, to remove the cervix and uterus. Sometimes, the ovaries, fallopian tubes and lymph nodes in the vicinity, if affected, are also removed during the same session.

There are four types of hysterectomies done:

• Total abdominal hysterectomy: An incision or cut is made in the abdomen to access the uterus and thereafter remove it.
• Vaginal hysterectomy: The uterus is removed through the vagina.
• Radical hysterectomy: If cancer has metastasized to the cervix and top part of the vagina, the gynaecologic oncologist removes the uterus first followed by some tissue close to the uterus. Then he/she will remove the top portion of the vagina, close to the cervix.
• Minimally invasive hysterectomy: The surgeon makes more than one tiny incision in the abdomen to access the uterus. Then using a laparoscope or a robot, the uterus is carefully removed.

Targeted Therapies 

Several targeted therapies are being explored for endometrial cancer: 

1. PARP inhibitors: Effective in POLE ultra mutated and MSI high subtypes.
2. PI3K/AKT/mTOR inhibitors: Showing promise in copy number high (serous-like) subtype.
3. Immunotherapies: Being investigated in MSI high and copy number high (serous-like) subtypes.

Precision Medicine 

Molecular classification has paved the way for precision medicine in endometrial cancer:

1. Personalized treatment: Treatment strategies tailored to individual molecular profiles.
2. Predictive biomarkers: Molecular markers to predict treatment response and prognosis.
3. Ongoing research: Continuous exploration of new molecular targets and therapies.

By integrating molecular classification into clinical practice, we can improve treatment outcomes and provide more personalized care for patients with endometrial cancer.

For comprehensive and advanced care for Uterine Cancer, consider consulting with the expert gynaecologic oncologists at Kauvery Hospital. With branches in Chennai, Hosur, Salem, Tirunelveli, and Trichy, they are dedicated to providing high-quality, personalized healthcare solutions to all patients.

Frequently Asked Questions 

What is uterine cancer?
It is cancer that starts in the uterus, often in the inner lining (endometrium).

What are the main types of uterine cancer?
There are two types:

– Endometrial cancer (about 95% of cases)
– Uterine sarcoma (about 5% of cases)

What are common symptoms of uterine cancer?
Common signs include unusual vaginal bleeding (especially after menopause), pain in the pelvic area, and changes in menstrual periods.

How is uterine cancer diagnosed?
Doctors use a pelvic exam, imaging tests (like ultrasounds or CT scans), and a biopsy (a small tissue sample) to diagnose it.

What treatment options are available?
Treatments include surgery (removing the uterus), chemotherapy, radiation therapy, hormone therapy, and sometimes targeted or immunotherapy.

What factors increase the risk of uterine cancer?
Risk factors include being over 50, obesity, hormonal imbalances, early menstruation or late menopause, and a family history of cancer.

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