What is uterine cancer?

A woman has a uterus or womb at the top of the vagina, it comprises a cervix (neck) and body or corpus and has a fallopian tube arising from each side at the top, it is these specialized structures that carry the fertilised ovum from the ovary to the uterus where development of the child occurs. After puberty the uterus goes through approximately monthly cycles in which the lining of the uterus is stimulated to grow by oestrogen originating in the ovary.After ovulation, a second hormone called progesterone is also secreted causing the lining of the uterus to stop growing. If this does not occur and pregnancy is not established, the hormonal stimulation stops and the lining of the uterus is partly shed at menstruation. This cyclical process continues until ovarian function declines and ceases at the menopause, however the lining of the uterus remains capable of responding to stimulation with oestrogen or oestrogen like substances.

What is Cancer?

Cancer cells are very similar to cells of the organism from which they originated and have similar (but not identical) DNA and RNA. This is the reason why they are not very often detected by the immune system, in particular if it is weakened. Cancer cells usually have an increased ability to divide rapidly and their number of divisions is not limited by telomeres on DNA (a counter system to limit number of divisions to 40-60). This can lead to the formation of large masses of tissue and in turn may lead to disruption of bodily functions due to destruction of organs or vital structures.

How is Cancer formed?

Cancer cells are formed from normal cells due to a modification / mutation of DNA and/or RNA. These modifications / mutations can occur spontaneously (II Law of Thermodynamics - increase of entropy) or they may be induced by other factors such as: nuclear radiation, electromagnetic radiation (microwaves, X-rays, Gamma-rays, Ultraviolet-rays, etc.), viruses, bacteria and fungi, parasites (due to tissue inflamation/irritation), heat, chemicals in the air, water and food, mechanical cell-level injury, free radicals, evolution and ageing of DNA and RNA, etc. All these can produce mutations that may start cancer. Cancer can be called therefore "Entropic Disease" since it is associated with the increase of entropy of the organism to the point where the organism cannot correct this itself. External intervention is required to allow the organism to return to an stable entropic state.Cancer cells are formed continuously in the organism (it is estimated that there are about 10,000 cancer cells at any given time in a healthy person). The question is why some of these result in macroscopic-level cancers and some don't. First, not all damaged cells can multiply and many of them die quickly. Those which have the potential to divide and form cancer are effectively destroyed by the various mechanisms available to the immune system. This process takes place continuously.
Therefore cancer develops if the immune system is not working properly and/or the amount of cells produced is too great for the immune system to eliminate. The rate of DNA and RNA mutations can be too high under some conditions such as: unhealthy environment (due to radiation, chemicals, etc.), poor diet (unhealthy cell environment), people with genetic predispositions to mutations and people of advanced age (above 80).

How is uterine cancer diagnosed and staged?

Abnormal vaginal bleeding must always be thoroughly investigated in a manner that includes taking a sample of the lining of the uterus. A pap smear is an unreliable means of investigating possible cancer of the endometrium and is not used for this purpose. Physical examination of the lower genital tract (vulva, vagina and cervix) should be performed to exclude other local causes of bleeding. A pelvic ultrasound examination may also be performed at this stage.
Direct examination of the lining of the uterus by hysteroscopy has become the most common means of diagnosing cancer of the lining of the uterus. In essence a thin instrument attached to a television camera is introduced along the vagina and through the cervix into the uterine cavity allowing thorough examination of the uterine cavity and allowing any abnormal areas to be sampled.
This may be performed as an outpatient with or without sedation or may be performed under light general anaesthesia in an operating theatre in a hospital or a day surgery unit. Sampling of abnormal areas my be undertaken by direct biopsy or scraping the suspicious areas or by curettage of the entire endometrial lining during the procedure.
Hysteroscopy also allows evaluation of the extent of a cancer in the endometrial cavity in so far as it can give an indication of how much of the lining is involved and whether there is direct extension to the cervix.The tissue collected at this procedure will be examined by an expert pathologist and may even be sent to a sub specialist pathologist with a particular interest in gynaecological oncology. Once cancer of the uterus has been diagnosed or confirmed you should be referred to a Certified Gynaecological Oncologist for further management and treatment.While awaiting this appointment you may have some blood tests as well as radiological examinations performed, these may include chest X-ray and may also include CT scanning of your abdomen and pelvis. Other tests that may be peformed include an MRI or a PET scan.
If cancer is confirmed further surgery is undertaken and this will be outlined below. Briefly the role of surgery in early cancer is to see if the cancer has spread to any other tissues including the lymph nodes. In more advanced cancer the role of surgery is to remove all or as much cancer as possible.Once the surgery is performed, patients are assigned a clinical stage known as the FIGO stage. This allows us to give our patients some idea as to the likelihood of success of treatment and to compare our treatments with other cancer groups around the world. An abbreviated FIGO staging system is shown.
Generally speaking the higher the stage, the more that the cancer has spread and the more serious the cancer.
Stage I: the cancer is confined to the uterus
Stage II: the cancer involves the uterine body and cervix
Stage III: the tumour has spread to the outside of the uterus, to the vagina or the lymph glands.
Stage IV: the cancer has either spread to the lining of the bladder or bowel or spread to distant organs.

What are the symptoms of uterine cancer?

The commonest symptom of uterine cancer is post menopausal bleeding, that is any bleeding from the vagina more than twelve months after ceasing menstrual periods. It may also present as heavy irregular periods or as a water or bloody discharge, which may be smelly. Occasionally there is a sensation of pelvic or abdominal discomfort or even a feeling of bloatedness

What are the treatments for uterine cancer?

Surgery Almost all women with uterine cancer will have some type of surgery in the course of their treatment. The purpose of surgery is first to remove the cancer and provide tissue to stage the spread of the cancer. Generally, women with uterine cancer will have a hysterectomy (removal of the uterus) and bilateral salpingo-oophorectomy (removal of both ovaries and fallopian tubes) as part of their operation. This is because there is always a risk of microscopic cancer in both of the ovaries as well the uterus, as well as the possibility of there being a coexistent ovarian cancer. This is usually an abdominal procedure performed under general anaesthesia, however in certain situations it may be performed as a laparoscopic total hysterectomy or as a laparoscopic assisted vaginal hysterectomy both with bilateral salpingo-oophorectomy.
On entering the abdomen any free fluid collected or fluid is introduced to the pelvis and then collected and sent for microscopic examination as part of the staging procedure. The pelvic and abdominal contents are carefully inspected for any suggestion of spread (metastasis) of the cancer and for evidence of any other disease process. The lymph node chains along the major abdominal and pelvic vessels are palpated for any evidence of possible spread to them. The uterus, fallopian tubes and ovaries are now removed and the uterus is opened to ascertain the presence of muscular invasion. Depending on the precise tumour type and the depth of myometrial (muscular) invasion by the tumour a decision will be made regarding removal of pelvic and paraaortic lymph glands. In certain tumour types the omentum (a fatty apron that hangs from the stomach) may also be removed. The abdomen is closed at the end of the procedure and during the recovery process the removed tissues and organs are examined by the pathologist and a formal staging is attributed to the tumor as well as occasional revision of the precise nature of the tumor. When these facts become known further treatment options will be discussed by the tumour board and will be discussed with the patient.
Further therapy Even when all cancer is removed, there is always a risk that the cancer might return. Occasionally no further therapy is recommended, particularly in patients with low risk and early stage tumors with little or no chance of recurrence. However after careful staging and evaluation of the tumour further therapy is recommended as appropriate.RadiotherapyHigh energy x-rays are used to kill cancer cells. These come from a machine called a linear accelerator or linac for short. Treatment is usually given as an outpatient. The number of treatments varies but can be up to 5 days a week for to 6 weeks. The treatment takes just a few minutes, and it is painless.
Radiation can also be used to ease the pain of metastases and stop tumors from bleeding. Generally, doctors try to limit the amount of radiation that your vital organs receive, and don't like to treat large portions of the bowel and pelvis.Internal radiation therapy may also be given to deliver higher doses of radiation to the region of the cervix or the top of the vagina. This is called brachytherapy and may be given alone or in combination with external beam radiotherapy.
Chemotherapy In certain less common uterine cancers and sarcomas chemotherapy is used because of a high risk of disease spread or because of known disease spread. There are many different chemotherapy drugs, and they are often given in combinations. Patients will usually have to go to a clinic to get the chemotherapy because many of the drugs have to be given through a vein. Different chemotherapy regimens are used for different purposes. The most common drugs currently used, alone or in combination include Cisplatin or Carboplatin (platinum containing drugs) Adriamycin, Ifosfamide and Taxol. Sometimes new combinations are tried if there isn't a response to the original combination. There are advantages and disadvantages to each of the different regimens that your medical oncologist will discuss with you. Based on your own health, your personal values and wishes, and side effects you may wish to avoid, you can work with your doctors to come up with the best regimen for your cancer and your lifestyle. Our team will also discuss with you about being involved with the latest research into cancer treatment. You will need to consent for a research treatment. It involves being randomized or offered either the gold standard treatment or another combination of drugs that we believe is as good or better. It is through medical research and clinical trials that we have been able to advance cancer treatment.
Hormone therapy Hormone therapy is used occasionally in highly selected situations, which your oncologist will discuss with you. In most situations it has no demonstrated value, however it is sometimes used in recurrent disease. The most commonly used agents are Provera (medroxy progesterone acetate) and Tamoxifen. Occasionally severe menopausal symptoms will occur and if not controlled with alternate therapies it may be necessary to institute oestrogen replacement therapy. The very limited data available suggest no increased risk of recurrence or death. Follow-up testing After treatment is completed, patients are followed up closely and regularly to make sure the cancer does not return. This involves 3 monthly visits to start with. Your doctor will ask you some questions, perform an examination including a pelvic examination and may perform a blood tests (including CA125). Follow up CT scanning is not routinely performed but may be done if the doctor is unsure about his findings on examination or if the blood test starts to become elevated. Annual chest X-rays are often advised as well.
Other health screening should also be attended to especially breast surveillance by examination and regular mammography as well as screening for colonic cancer, both of which are increased in women who have had endometrial cancer.

Am I at risk of endometrial cancer?

Uterine or endometrial cancer is more common as women get older, particularly over the age of 50 and those who have gone through menopause (change of life). Other than age, the next most important risk factor for uterine cancer is body weight as a consequence of fat cells making weak oestrogens that stimulate the lining of the uterus. Women with a history of breast cancer also have an increased risk of developing uterine cancer. Some women who have a hereditary risk of cancer may also be at risk of developing bowel, breast and ovarian cancer as well. Women who have had many ovulations throughout their life are also statistically at an increased risk of developing uterine cancer. Starting puberty early, going through the change of life late or not having children or breast feeding and not having used the oral contraceptive pill will increase a women’s risk. Uterine cancer remains one of the most common cancers affecting women in New South Wales.

How can I prevent uterine cancer?

We can generally speaking cancer cannot be prevented. Can screen for pre-cancer and we are reasonably good at that with the mammogram for breast cancer and the Pap test for detecting precancer of the cervix. Unfortunately screening for uterine cancer is not very productive. However women with heavy or irregular bleeding at the time of menopause should be evaluated for the possibility of overgrowth of the endometrium or lining of the uterus and treated appropriately at that time. It is important to discuss your individual case with our expert team.

New Research in Cancer Treatment

Genetically engineered bacteria and virusesSome new promising research uses genetically engineered bacteria and viruses to infect and destroy cancer cells. This could be useful when cancer is already advanced and there are large masses of cancer cells. The potential drawback of these methods is the generation of large amounts of toxins from dying cancer cells, which in turn can suppress the immune system or even kill the patient. Also bacteria and viruses very often mutate which in turn can lead to infection and attack on healthy, non-cancerous cells.
Anti-cancer vaccines Anti-cancer vaccines or even custom-made anti-cancer vaccines for a particular patient and cancer type are also a very promising line of research. By providing fragments of cancer cells to the immune system, one can potentially get the immune system response to destroy live cancer cells. Cancer markers Another promising line of research is related to chemical substances which could be used to mark cancer cells. This in turn will allow easier recognition of these cells by the immune system.
Cancer growth retarders / inhibitors This line of research is related to the use of chemical substances which could retard / inhibit the growth of cancer cells. An interesting research topics are the substances blocking activity of telomerase, the enzyme responsible for the management/elongation of telomeres. Telomerase is found in high concentrations in 80% of tumors and allows tumor cells to gain "immortality" by removing restrictions on the number of cell divisions. This enzyme may also be useful in extending the lifespan of healthy cells and in turn extend the lifespan of the organism (cancer cells and their growth may hold much valuable information about fountain of youth and immortality).All the above mentioned methods show some promise. However these methods by themselves do not provide reliable cancer treatment. It is possible that some of them in conjunction with the non-traditional treatment of cancer (listed below) will become the standard cancer treatment, in the 21st or 22nd century.

"World Cancer Report" by Who

WHO (World Health Organization, division of UN) estimates that only 4% of all cancers are inherited /genetic and that the majority of cancers are preventable ("World Cancer Report", IARC Press, Lyon 2003). According to this report, various cancers are strongly linked to lifestyle and the environment. It lists many of these factors and carcinogens. Cancer world maps shown in the report illustrate that the majority of cancers are in developed countries which indicates again a strong link between cancer, lifestyle, diet and environment. This statistical data is very consistent with the cancer model outlined in this paper. "World Cancer Report" by WHO