What is Uterine Cancer?
Uterine cancer is one of the most common cancers of the female reproductive organs. Women who just pass menopause, most often between the ages of 50 and 70 years, are more likely to suffer from uterine or endometrial cancer. Abnormal vaginal bleeding is the most common symptom of this condition.
Although there are many risk factors associated with the development of cancer of the uterus, the female hormone estrogen is thought to play a particularly significant role. Endometrial cancer may run in some families. Early clinical symptoms, resulting in early diagnosis of uterine cancer, may offer a better chance of survival with prompt treatment.
- Uterine cancer is almost synonymous with endometrial cancer (cancer of the inner lining of the uterus) or endometrial carcinoma since almost all cancers of the uterus start in the endometrium.
- Cancer may also start in the supporting connective tissue (stroma) and muscle cells of the uterus and is then known as uterine sarcoma. This is relatively less common than endometrial carcinoma.
- Cervical cancer (cancer of the cervix) is a different entity from endometrial cancer.
Cancer in the Uterus
The uterus,or womb, is that part of the female reproductive system where the baby grows when a woman is pregnant. The upper part of the uterus is the body while the lower end, which extends into the vagina, is known as the cervix.
The body of the uterus has an inner lining known as endometrium. The muscular wall is called the myometrium, which is covered on the outside by the serosa.
Changes occur in the endometrium as a result of hormonal changes at different phases of the menstrual cycle. At the beginning of the cycle, there is increased estrogen level caused by secretion of estrogen by the ovaries. This causes the endometrium to thicken in preparation for implantation of the embryo, should pregnancy occur. If pregnancy does not occur, the estrogen level drops and by the end of the cycle the endometrial lining is shed and comes out as menstruation.
Uterine Cancer and Female Hormones
However, in most cases of endometrial cancer, the thickening of the endometrium remains as such. This condition is known as endometrial hyperplasia, which may be a precancerous stage of endometrial cancer. Hormonal imbalance is thought to be an important factor in the development of endometrial cancer. Unopposed estrogenic stimulation leads to endometrial hyperplasia, which may be reversible in the initial stages with hormonal therapy. However, persistent stimulation can lead to atypical hyperplasia followed by endometrial cancer.
Uterine cancer is when cells in a part of the body start growing out of control. These are abnormal cells and this uncontrolled growth heralds the beginning of cancer. More and more abnormal cells are formed which may invade other tissues. Cancer cells may start growing in any part of the body. Damage to DNA in the cell provokes a normal cell to become cancerous, which further produces new cells with damaged DNA.
Benign and Malignant Tumors of the Uterus
Cancer cells may form a tumor at the site of abnormal cell growth. This is known as a malignant tumor. Cancer cells may also travel to other parts of the body through the blood stream or lymph vessels and form new tumors there. This is known as metastasis and the tumors are metastatic tumors. Different types of cancers may behave differently and also respond to different ways to treatment. Malignant tumors may grow back even after removal and may become life-threatening.
Sometimes, tumors which are not malignant form in the uterus. These are known as benign or non-cancerous tumors like uterine polyps or uterine fibroids. Benign tumors do not invade other tissues and do not metastasize. Uterine cancer indicates a malignant tumor of the uterus. Women who have never got pregnant are seen to be more at risk of getting endometrial cancer. This could be due to the continuous hormonal onslaught on the endometrium through the years. This is interrupted when a woman falls pregnant since pregnancy causes amenorrhea or cessation of menstruation.
Types of Uterine Cancer
Endometrial cancer is the most common type of uterine cancer and starts in the inner lining of the uterus known as the endometrium.
Endometrial carcinomas can be divided into various subtypes, of which adenocarcinomas are the most common. Adenocarcinomas are cancers of the cells that form glands in the endometrium. Most endometrial carcinomas are typical adenocarcinomas, also known as endometrioid.
Other less common, but often more aggressive, subtypes are :
- Squamous cell carcinoma
- Papillary serous carcinoma
- Clear-cell carcinoma
- Poorly differentiated carcinoma
Cancer that starts in the supporting connective tissue (stroma) and muscle cells of the uterus is known as uterine sarcoma. Only a small percentage of uterine cancers belong to this group.
Uterine Carcinosarcoma (CS)
Another rarer type of uterine cancer is known as uterine carcinosarcoma (CS). CS also starts in the endometrium but shows features of both carcinoma and sarcoma when examined under the microscope. It has been suggested that CS may be a form of poorly differentiated carcinoma.
Based on their prognosis (outlook) and underlying cause, endometrial carcinoma may be divided into 2 types
- Type 1 cancers are those that are caused by an excess of the female hormone estrogen. These are less aggressive than type 2 cancers and since spread to other tissues is usually slow, the outlook is often better than type 2 cancers. Grades 1 and 2 endometrioid cancers belong to this group. Type 1 endometrial cancer is the most common type, accounting for nearly 80% of cases.
- Type 2 cancers are not estrogen dependent, although the exact cause is not known. Serous carcinoma, clear-cell carcinoma, poorly differentiated carcinoma, and grade 3 endometrioid cancers fall under this group. These cancers are more aggressive and tend to spread more rapidly hence their prognosis is not as good as type 1 cancers.
Causes and Risk Factors of Uterine Cancer
The exact cause of uterine cancer is not known but some factors cause a genetic mutation to occur within the cells of the endometrium, changing normal cells into abnormal cells.
The factors that may contribute to the development of uterine cancer includes :
- Age. Uterine cancer is a disease that is more often seen in older women. Women between the ages of 50 and 70 seem to be more at risk. It rarely develops in women under the age of 40.
- Family history. Uterine cancer tends to run in some families.
- Persistently high estrogen levels seem to play a significant role. Many of the risk factors for uterine cancer affect estrogen levels. A change in the balance of the two hormones, estrogen and progesterone, with a shift towards more estrogen, may increase a woman’s chances of developing endometrial cancer.
- Menopause. Changes in hormone levels during menopause may be the reason that endometrial cancer is more common in postmenopausal women.
- Early menarche (onset of menstruation). More years of menstruation, typically when menarche occurs before the age of 12 years and late menopause, after the age of 50, may raise a woman’s risk of endometrial cancer.
- Hormone replacement therapy (HRT). Women who are only on estrogen, without the use of progesterone, seem to be at considerable risk. The unopposed action of estrogen on the endometrium for a prolonged period may lead to the development of uterine cancer.
- Oral contraceptives, especially when used for a long time, may lower and not increase the risk of endometrial cancer. This protective action may continue for over 10 years after stopping the pills.
- Pregnancy causes a shift in the balance of hormones towards more progesterone hence women who have been pregnant a number of times may be protected against uterine cancer.
- Nulliparous women are those women who have never been pregnant and the risk of uterine cancer seems to be higher, especially when associated with infertility.
- Tamoxifen. Women who are on or have recently been on the drug tamoxifen used in the treatment of breast cancer may increase the risk of uterine cancer. However, in most cases, the benefits of tamoxifen outweigh its risk.
- Obesity is a major risk for uterine cancer.
- Diabetes mellitus (sugar diabetes).
- High blood pressure.
- History of uterine polyps.
- Women with hereditary nonpolyposis colon cancer (HNPCC) have a high risk of endometrial cancer.
- Endometrial hyperplasia (overgrowth of the endometrium), brought about by persistently high estrogen levels. Simple hyperplasia is not precancerous but atypical hyperplasia has a higher chance of becoming cancerous.
- Estrogen-producing ovarian tumors.
- Polycystic ovarian syndrome (PCOS), where there is a higher estrogen level in comparison to the progesterone level.
- History of breast cancer or ovarian cancer increases risk of uterine cancer.
- Pelvic radiation given to treat some other cancer can cause damage to the DNA of cells, thus increasing risk of developing cancer.
Signs and Symptoms of Uterine Cancer
Abnormal Uterine Bleeding
This is the most common presentation of uterine cancer. This may manifest as :
- Postmenopausal bleeding or spotting.
- Bleeding in between periods (intermenstrual bleeding).
- Prolonged, heavy, or frequent periods, especially after the age of 40.
- Thin white or blood tinged vaginal discharge after menopause.
- Bleeding after intercourse (post-coital bleeding).
It is extremely important to remember that any vaginal bleeding after menopause is definitely not normal and should be investigated immediately, even though all postmenopausal bleeding may not be a sign of cancer.
- Lower abdominal or pelvic pain.
- Pain during or after intercourse.
- Pain while passing urine.
Other Signs and Symptoms
- Feeling a mass or lump in the lower abdomen or pelvis.
- Unintentional weight loss, especially if it is continuous.
Grading of Uterine Cancer
Grading helps to determine how much the tumor tissue differs from normal uterine tissue. It can help to indicate which tumors are more likely to grow rapidly. Grade indicates aggressiveness of the cancer. Tumors with higher grades usually grow more rapidly, are more likely to metastasize and recur after treatment.
Grading of a tumor is useful in deciding the type of treatment that will be most suitable for that particular patient. It is done by examining the tissue samples from the uterus under a microscope.
- Grade 1 (low grade) – the cells are quite similar to normal endometrial cells and are said to be “well-differentiated”. They are usually slow-growing and are least aggressive.
- Grade 2 (middle grade) – this is the intermediate grade.
- Grade 3 (high grade) – the cells look abnormal and are said to be “poorly-differentiated”. These cells grow rapidly and are most aggressive.
Staging of Uterine Cancer
Staging of a cancer is important in deciding on the best treatment options. It also indicates the outcome of the disease. Staging is a system that helps to determine how far the cancer has spread, whether it is limited to the nearby tissues or has spread to distant tissues and organs. The cancer may spread :
- Locally to other parts of the uterus.
- Regionally to nearby lymph nodes in the pelvis and the lymph nodes along the aorta.
- Metastasize to distant lymph nodes or organs such as lungs, liver and brain.
For staging of uterine cancer certain tests may be helpful, such as :
- Pap test to see if cancer has spread to the cervix.
- Chest x-ray to see if the lungs are involved.
- CT scan or MRI can diagnose spread of cancer to different organs.
Another method of staging of uterine cancer is known as surgical staging. It is a post-operative procedure where the staging is done based on examination of tissue removed during operation. This includes tissue samples taken from the pelvis and abdomen, and the uterus (which may be cut open to see the extent of growth).
Either way, staging is done on the basis of these 3 factors :
- The extent of tumor (T).
- Whether the cancer has spread to lymph nodes (N).
- Whether the cancer has spread to distant sites (M).
Tumor Extent (T)
- T0 – there is no sign of cancerous growth in the uterus.
- Tis – cancer-in-situ or pre-invasive cancer – only the surface layer of the endometrium shows cancerous cells, with no involvement of the deeper layers.
- T1 – the cancer is restricted to the body of the uterus.
- T2 – the cancer has spread from the body of the uterus to the supporting connective tissue of the cervix, but has not spread outside the uterus.
- T3 – the cancer has spread outside the uterus but has not reached the inner lining of the bladder or rectum.
- T3a – the cancer has reached the outer layer of the uterus and/or the fallopian tubes and ovaries.
- T3b – the cancer has spread to the vagina or the tissues around the uterus.
- T4 – the cancer has spread to the inner lining of the bladder or rectum.
Lymph Node Spread (N)
- NX – spread of cancer to nearby lymph nodes cannot be assessed.
- N0 – there is no spread of cancer to nearby lymph nodes.
- N1 – the cancer has spread to the pelvic lymph nodes.
- N2 – the cancer has spread to lymph nodes along the aorta.
Distant Spread or Metastasis (M)
- M0 – the cancer has not spread to distant lymph nodes, tissues or organs.
- M1 – the cancer has spread to distant organs such as the lungs, liver or brain.
Staging is done by compiling all the information together about tumor extent, spread to lymph nodes, and distant spread of cancer. Thus, endometrial cancer can be classified into the following stages :
- Stage 0 – carcinoma in situ where cancer cells are found only on the surface layer of the endometrium.
- Stage 1 – the tumor has grown through the endometrium and may have invaded the muscle layer of the uterus.
- Stage 2 – the tumor has invaded the cervix.
- Stage 3 – the tumor has grown through the uterus to invade nearby tissues such as the vagina or the pelvic lymph nodes.
- Stage 4 – the tumor has invaded the bladder or bowel, or has reached distant sites such as the lungs, liver, brain or bones.
Survival Rate and Prognosis in Uterine Cancer
The prognosis or outlook for patients with uterine cancer is referred to as their survival rate. It is generally discussed as the 5-year survival rate, which is the percentage of women who live at least 5 years after the cancer is diagnosed. This includes patients who live much longer than 5 years.
The 5-year survival rates are determined by follow-up of a large number of patients for more than 5 years. This gives only an approximate estimate since newer treatments for cancer can improve the rate. Individual factors also need to be considered and one woman’s response to treatment can vary greatly from another woman’s. Many other factors are also involved, such as the health of a person at the time of diagnosis and the type of cancer.
The 5-year survival rate for endometrial cancer which has not spread can be as high as 95%. Spread to distant organs results in a sharp fall in 5-year survival rate, which can be as low as 23% or even less. Due to increasing patient awareness about the early signs and symptoms of endometrial cancer, and as a result of early cancer detection in most cases, the outcome is usually good.
- The prognosis of patients with Type 1 endometrial cancer – a slow-growing cancer, said to be dependent on estrogen – is very good as it is usually detected early.
- Type 2 endometrial cancer, which is fast-growing and more aggressive than the Type 1 variety, is more often detected at an advanced stage hence the outlook is more grim in these cases.
Recurrence of uterine cancer even after successful treatment is a possibility and most recurrences occur within 2 years. Usually, low grade tumors are less likely to metastasize or recur after treatment. Recurrence in early-stage disease is most often seen at the vaginal cuff and pelvis. Surgical excision, radiation therapy, or a combination of both may be done in these cases.
Endometrial cancer treated with surgery alone tends to show recurrences confined to the pelvis, whereas treatment done with surgery and radiotherapy are more likely to show less localized recurrences with more involvement of the lungs, liver, bones, brain, abdomen, and lymph nodes. Surgical excision and radiation therapy are less effective in these cases, and hormone therapy or chemotherapy may give better results.