Anal cancer arises from the anus, the distal orifice of the lower gastrointestinal tract. It is a distinct and completely different disease entity from the more common colon and rectal cancers.
Cancer of the anus is rare. Less than 800 people are diagnosed with this type of cancer each year in the UK. As with most cancers the cause of most anal cancers is unknown. It is slightly more common in women than men.
The origin, risk factors, clinical progression, staging, treatment and prognosis are all different. Anal cancer is typically a squamous cell carcinoma (not an adenocarcinoma) that arises in or around the anus. They are subdivided into anal canal tumours or anal margin tumours. Some early anal margin tumours can be treated more like skin cancers. The tumours can be further subdivided depending on what they look like under the microscope.
Risk factors for anal cancer
- Human Papilloma Virus (HPV) infection: A high proportion of anal cancers (up to 90% in some studies are positive for the same types of HPV that are also associated with high risk of cervical cancer
- Sexual activity: Having multiple sex partners or having anal sex, due to the increased risk of exposure to the HPV virus.
- Smoking: Current smokers are several times more likely to develop anal cancer compared with non smokers.
- A lowered immune system, which is often associated with HIV infection.
- Benign anal lesions. Inflammation resulting from benign anal lesions, such as hemorrhoids and anal fistulas, has been considered to cause a predisposition to anal cancer although this is contraversial
- Homosexual Men are up to 17 times more likely to develop anal cancer than heterosexual men.
Signs and symptoms
The most common symptoms of anal cancer are pain and bleeding from the anus. Some people develop small, firm lumps which may be confused with piles (haemorrhoids).
Other symptoms can include discomfort, itching and a discharge of mucous from the anus. Faecal incontinence (a reduced ability to control bowel function) may also occur. Anal cancer can appear as an ulcerated area and may spread to the skin of the buttocks.
How it is diagnosed
Usually you begin by seeing your GP who will examine you and refer you to a specialist.
At the hospital the doctor will ask you about your general health and any previous medical problems. They will also examine you and take blood samples to check your general health. Before the doctor can make a firm diagnosis of anal cancer a number of tests will have to be done.
Rectal examination
This is also sometimes known as a PR examination and is where the doctor examines your back passage with a gloved finger. This gives important information on the location and extent of the tumour.
Biopsy
A small sample of tumour tissue is taken so that it can be examined under a microscope to confirm the suspected diagnosis. Usually this involves using either a special biopsy device (known as a punch biopsy) or the doctor can cut a small piece away from the tumour (known as an incisional biopsy). This can be done under local or general anaesthetic.
If the tests show that you have anal cancer, you may need further tests to see if the cancer has spread or is well localised.
Ultrasound scan
You may have a specialised ultrasound scan known as an endoanal ultrasound. For this scan a small probe is passed into the back passage (rectum), which can show the size and extent of the tumour and lymph nodes.
CT scan
This is a more sophisticated type of x-ray scan which builds up a three-dimensional picture of the inside of the body. The scan is painless, but takes longer than a simple x-ray (10–30 minutes). It may be used to identify the exact site of the tumour or to check for any spread of the cancer to other organs. Most people who have a CT scan are given a drink or injection to allow the bowel and blood vessels to be seen more clearly. Before having the injection or drink, it is important to tell the person doing this test if you are allergic to iodine or have asthma.
MRI (magnetic resonance imaging) scan
This test is a type of scan, but uses magnetic fields instead of x-rays. During the scan you will be asked to lie very still on a couch inside a metal cylinder. You will usually be given an injection to allow the pictures to be seen more clearly. MRI gives the best pictures of anal cancers, and so allows the doctors to have a much better idea of the best treatment.
The test can take about 30 minutes and is completely painless, although the machine is quite noisy. You will be given earplugs or headphones. If you don’t like enclosed spaces you may find the machine claustrophobic. A two-way intercom enables you to talk with the people controlling the scanner.
MRI is also used to assess the effects of radiotherapy for anal cancers. Sometimes it can be used to image the liver if the CT scan has picked up something suspicious but it is unclear.
PET scan.
This is a highly specialised scan which is only done on some patients. An injection of radioactive sugar is given. Cancer cells are more active as they are dividing rapidly and so preferentially take up the radioactive sugar. A special camera (called a gamma camera) can pick up the emissions from the radioactive sugar within cancer cells and a picture of the cancer distribution within the body is produced. This test is usually only performed if there is uncertainty from the other tests whether cancer has spread, however it is being increasingly used in anal cancer as a confirmatory test as well.
Staging
The stage of a cancer is a term used to describe its size and whether it has spread beyond its original site. Knowing the particular type and the stage of the cancer helps the doctors to decide on the most appropriate treatment.
Cancer can spread in the body, either in the bloodstream or through the lymphatic system. The lymphatic system is part of the body’s defence against infection and disease. The system is made up of a network of lymph glands (also known as lymph nodes) that are linked by fine ducts containing lymph fluid. Your doctors will usually check the nearby lymph nodes when staging your cancer.
- Stage 1 The cancer only affects the anus and is smaller than 2cm (¾in) in size. It has not spread into the sphincter muscle.
- Stage 2 The cancer is bigger than 2cm (¾in) in size, but has not spread into nearby lymph nodes or to other parts of the body.
- Stage 3A The cancer has spread to the lymph nodes close to the rectum, or to nearby organs such as the bladder or prostate or vagina.
- Stage 3B The cancer has either spread to the lymph nodes in the groin and pelvis, or to the lymph nodes close to the anus, as well as nearby organs such as the bladder or prostate or vagina.
- Stage 4 The cancer has spread to lymph nodes in the abdomen or to other parts of the body, such as the liver or lungs.
A different staging system called the TNM staging system is sometimes used instead of the number system described above.
- T describes the size of the tumour and whether it has spread into nearby organs.
- N describes whether the cancer has spread to the lymph nodes.
- M describes whether the cancer has spread to another part of the body, such as the liver (secondary or metastatic cancer).
Although this system is more complex, it can give more precise information about the tumour stage, and is more commonly used by doctors.
If the cancer comes back after initial treatment, this is known as recurrent cancer.
Grading
Grading refers to the appearance of the cancer cells under the microscope and gives an idea of how quickly the cancer may develop. Low-grade (well differentiated) means that the cancer cells look very like normal cells. They are usually slow-growing and are less likely to spread. In high-grade (poorly differentiated) tumours the cells look very abnormal, are likely to grow more quickly and are more likely to spread.
Treatment overview
Patients with an anal cancer are treated by a specialist team. Such teams aren’t available in all hospitals, so you may have to travel to another hospital for your treatment.
The main type of treatment used for anal cancer is a combination of radiotherapy and chemotherapy, which may be given at the same time. This combination of treatment is usually very successful.
Surgery may be used, but it is not often the first choice of treatment for anal cancer, as studies have shown that chemoradiotherapy is extremely effective and can cure a high proportion of cases. The recent ACT2 clinical trial initial results were published in May 2009, and showed that around 75% of patients overall with anal cancer are cured by chemoradiotherapy. Of course the cure rate depends on the stage of the cancer.
Benefits and disadvantages of treatment
If you have been offered treatment that aims to cure your cancer, deciding whether to have the treatment may not be difficult. However, if a cure is not possible and the treatment is to control the cancer for a period of time, it may be more difficult to decide whether or not to go ahead.
If you feel that you can’t make a decision about treatment when it is first explained to you, you can always ask for more time to decide.
HIV and treatment
People who have a lowered immunity because of HIV, as well as having anal cancer, may get more side effects during and after treatment. As a result, the amount of radiotherapy and dosages of chemotherapy may be reduced. Your specialist can give you more information.
Radiotherapy
Radiotherapy is the use of high-energy rays to destroy cancer cells, while doing as little harm as possible to normal cells. The treatment is often given for a few minutes each weekday for between 5–6 weeks. Radiotherapy today is given in a targeted fashion to reduce side effects. Having said that, radiotherapy for anal cancer often involves treating large areas to treat the groin lymph nodes in addition to the anus, which can increase the toxicity. If you have an early T1 or T2 anal cancer it may be possible to receive radiotherapy to a smaller area, but this technique is not practiced in all centres. Your oncologist will discuss this with you.
There are technical ways that the oncologist can reduce the volume of normal tissue treated. This can be done using conformal CT planning to the pelvis, and a different type of radiation, called electron radiation, can sometimes be used to treat the groins. Recently, some studies have shown that intensity modulated radiotherapy (IMRT) can greatly reduce the side effects of treatment, and its use will likely increase in the future.
Radiotherapy for anal cancer is most commonly given over 28 fractions in 5 and a half weeks, although sometimes boosts are given at the end in advanced disease.
During the treatment period you may have changes in how your bowel works such as diarrhoea, or passing wind: these side effects can sometimes be reduced by avoiding particular foods. Towards the end of the treatment period you may have blistering and soreness of the skin around the anal area, and possibly in the groin areas too. Soreness can also occur over the scrotum in men and vagina in women. The soreness can be particularly severe when you open your bowels. Often, a feeling of incomplete emptying of bowels can occur due to all the inflammation. Tiredness is also a common side effect of radiotherapy for anal cancer.
These side effects usually decrease gradually once the treatment has ended, but it may take some months for skin changes to go back to normal. A few people find that the way their bowel works is permanently altered.
Most patients need special skin creams and dressings towards the end of treatment, and pain killers are also given if necessary, with anti-diarrhoea medication.
Other potential side effects that can occur late after radiotherapy has been completed for anal cancer include narrowing of the vagina (vaginal stenosis), and vaginal dryness. To help prevent this, women will be asked to use a vaginal dilator with a lubricating jelly to keep the vaginal walls open and supple. Some women may also need to use lubricating jelly during sexual intercourse.
Infertility (loss of the ability to have children) can also be a side effect of radiotherapy. If you are concerned about your risks of being infertile following treatment, it is a good idea to discuss this issue with your specialist before starting treatment.
Men can become impotent following radiotherapy for anal cancer as the sexual nerves within the pelvis can be damaged. Often this is only partial and responds well to medical treatment. Complete permanent impotence following this treatment is unusual.
Chemotherapy
Chemotherapy in anal cancer is given together with the radiation. It increases the toxicity of the treatment overall, but there is no doubt it adds significantly to the effectiveness of therapy. The drugs most commonly used are Mitomycin-C , usually given on day 1 of radiotherapy, and 5FU, given as an infusion in the 1st and last (5th) week of radiotherapy through a pump. Some doctors are now using oral capecitabine as a substitute for the 5FU infusion, and some use cisplatin as a substitute for mitomycin. Information on all these drugs can be found in this website.
Recently published data from the ACT2 trial shows no difference between mitomycin and cisplatin in terms of effectiveness, and no benefit to additional chemotherapy after the end of the radiotherapy. In this study 95% of patients had a complete response of their tumour 6 months after treatment, and the 3 year disease free rate was 75% – This proportion of patients have probably been cured. So the cure rate for anal cancer without surgery is very high.
Surgery
Surgery may be used if your initial treatment does not completely get rid of the cancer, or if there are signs that your cancer has returned. As you can see from the ACT2 study above, this is becoming increasingly rare. There are two main types of surgery: local resection and abdominoperineal resection.
Local resection
This may be used for small tumours on the outside of the anus. This operation only removes the area of the anus containing the cancer cells. The anal sphincter is not usually affected, and so bowel function is not usually affected.
Abdominoperineal resection
This is the removal of the anus and rectum. This operation requires a permanent colostomy, which involves diverting the open end of the bowel on to the surface of the abdomen to allow faeces to be passed out of the body into a colostomy bag. The opening on the abdominal wall is known as a stoma.
See the section on rectal cancer for more information on this operation.
Prevention
Since many, if not most, anal cancers derive from human papilloma virus infections, and since the HPV vaccine prevents infection by several strains of the virus, scientists surmise that HPV vaccination will prevent anal cancer in the same way it protects against cervical cancer. There is no hard data yet on this, but some preliminary studies from north America suggest there may be a benefit. The HPV vaccine is currently given to teenage girls – It will be many years before we see a drop in anal cancers and know for sure whether the vaccine works in this indication. Some homosexual men, who are at high risk, have been having the HPV vaccine privately but the numbers are too small to know whether it makes a difference yet.
Metastatic or recurrent disease
Up to 10% of patients treated for anal cancer will develop distant metastatic disease. Metastatic or recurrent anal cancer is difficult to treat, and usually requires chemotherapy.
Radiation is also employed to palliate specific locations of disease that may be causing symptoms.
Prognosis
The ACT2 trial suggests up to 75% patients are cured overall. Survival also depends upon stage. For example the cure rate for a T1 N0 tumour will be close to 100%, whereas for a T4 N2 is likely nearer to 40 – 50%