The anus is the canal that connects the lower part of the large intestine (the rectum) to the outside of the body. Anal cancer is fairly rare. Different cancers can develop in different parts of the anus, part of which is inside the body and part of which is outside. Sometimes abnormal changes of the anus are harmless in their early stages but may later develop into cancer. Some anal warts, for example, contain precancerous areas and can develop into cancer. The most common type of anal cancer is squamous cell carcinoma of the anus.
The disease is more common in people who have anal intercourse and there is an association with human papilloma virus infection as well HIV, although a causative link has not firmly been established. There are many types of human papilloma virus and only a few of these types seem to be linked to the development of anal cancer. Those that are linked to these viruses have a similar prognosis to those that are not.
Long term immunosuppression, eg in those who have had organ transplants, also increases the risk of developing anal cancer
Smoking increases the risk of developing Anal Cancer by between 2- and 5- fold.
The development of anal cancer does not seem to be linked to haemorrhoids (piles), anal fissures or fistulae. The link with inflammatory bowel disease (Crohn’s Disease or Ulcerative Colitis) is controversial.
Anal cancer is rare tumour and only 300 new cases arise each year in the UK. It is therefore a less serious health problem than colorectal cancer.
Symptoms & diagnosis: Anal cancer
The symptoms of anal cancer may be:
- The sensation of a lump
- Itching of the skin around the anus
- Changes in existing anal warts
Many of these symptoms may be caused by benign conditions e.g. haemorrhoids or and anal fissure, so thorough examination is important.
The diagnosis is confirmed by taking a sample of the lump or suspicious region, and having this examined under a microscope by a specialist. The biopsy may be taken in the outpatient clinic, but usually a full examination of the area is undertaken whilst the patient is under anaesthetic. This allows a much more thorough examination to be done. The biopsy can be taken during this procedure.
Other tests that are done include a CT scan of the chest, abdomen and pelvis, and an MRI scan of the pelvis.
The ‘stage’ of the cancer defines whether the tumour is localised to the anus or whether it has spread to the local lymph nodes (usually the groin nodes or pelvic nodes) or whether it has spread to other organs. The treating oncologist needs to know the stage to decide the most suitable treatment.
The information needed to decide the stage is gathered from both clinical examination and scanning. An examination under anaesthetic is often done to obtain the most accurate stage.
The stage is usually classified using a system called the ‘TNM Staging System’, where T stands for tumour, N for ‘nodes’ (ie lymph nodes), and M for ‘metastases’ (ie whether other organs are involved). Each letter is followed by a number that defines the extent of the cancer eg T2N1M0.
Treatment & outcomes: Anal cancer
Treatment for anal cancer is dependent on the stage of the disease and on the aim of the treatment. When the disease is localised it is potentially curable.
Treatment options include surgery to remove the anus, or a combination of radiotherapy and chemotherapy given simultaneously. Specialised locally delivered radiotherapy (brachytherapy) has been used for very small anal tumours as well.
The usual treatment that is chosen is combination of chemotherapy and radiotherapy, called chemoradiotherapy. This treatment has a major advantage over surgery in that most patients do not require a colostomy bag permanently. When surgery is performed with the aim of curing anal cancer, the anus itself is removed as well. With chemoradiotherapy, the organ is preserved. Another advantage of using chemoradiotherapy as the first treatment is that, surgery is still available as a curative treatment if the disease returns in the anus.
The radiotherapy is usually given on a daily basis, Monday to Friday, in a specialist department. It will involve lying still on a couch in a treatment room, whilst a treatment machine, gives the radiotherapy. The treatment does not hurt and is invisible. It does not make patient s radioactive. Each treatment lasts about fifteen minutes. Often, the bladder is kept full during the treatment to minimise the amount of radiotherapy given to the small bowel.
Before radiotherapy starts, there are a number of sessions that are undertaken to work out how to aim the radiotherapy to the areas that need to be treated. Often the first visit is to make sure the position is correct (sometimes lying on the front), and a specialised CT scan done with the patient in that position (this usually only takes 45 minutes to do). The scans are then worked on by the radiotherapy department, using sophisticated computer software, so as to get the best ‘plan’ for the treatment and the best treatment beam orientation. This can take 2 to 3 weeks to do. After a series of checks, the patient is given another appointment for a ‘dummy run’ of the treatment to make sure everything lines up accurately. The actual treatment then starts shortly afterwards.
The chemotherapy is usually given in the first and last week of the 5 and a half weeks of daily radiotherapy treatment. The chemotherapy may be given as an in-patient and will usually include two of the following anti-cancer drugs: 5-fluorouracil, mitomycin or cis-platin. A trial that looked at whether the continuation of chemotherapy, after the end of radiotherapy, increased the cure rate – came to the conclusion that such extra chemotherapy did not improve on chemoradiotherapy alone. This remains standard of care.
Chemoradiotherapy is a complex treatment and has many side effects. Most side effects disappear a few weeks after the treatment is completed, but some may last many months or be permanent.
The side effects of radiotherapy include:
- Sore skin, and peeling of the skin near the anal area and in the groins
- Pain around and in the anus
The combination of the diarrhoea and the sore skin around the anus means that a temporary colostomy is occasionally recommended to make these side effects easier to manage.
These effects usually improve in the weeks after the treatment is completed, although the way the bowel works may not return to normal completely.
Side effects that may be long term or permanent include:
- Vaginal narrowing and dryness: this can affect sexual function after treatment. It is important to see a specialist nurse before and during treatment who may advise using a vaginal dilator to minimise the risk of this side effect as much as possible.
- Infertility: this should be discussed with the oncologist if it is an issue.
- All the potential risks and side effects should be discussed by the oncologist.
Side effects of chemotherapy include:
- nausea and vomiting: this can be reduced by anti-sickness medication given with the chemotherapy
- sore mouth: mouthwashes can be given to help this
- loss of appetite
- a low blood count: if this happens, the body’s defences against infection can be reduced, which in turn means any infection may become more serious.
Having said all this, the chemoradiotherapy saves many hundreds of people the need to have an operation at the end of which they are left with a colostomy for life and most retain a continent and decent functioning anal sphincter.
The outcome of treatment depends on the stage of the disease and the response to treatment, but the majority of those with early disease stand a very good chance of cure.
The advantage of the chemo-radiotherapy programme is that it allows the patient to keep the normal anatomy of the rectum and anus; in the majority of cases (where the sphincter has not been destroyed by the cancer) the patient keeps an intact sphincter (and hence remains continent of faeces).
If the disease returns locally after chemoradiotherapy, then surgery may be is possible with the aim of curing. In this eventuality, the patient will have removal of the ano(rectum) and be left with a colostomy
What to do if there is metastatic relapse after the foregoing therapy?
Alternative chemotherapy should be trialled but it is also worthwhile considering other options.
Genomic analysis by next generation sequencing of a new tissue biopsy of cell-free DNA (which is often released from the turning-over cancer cells into the blood stream and can be analysed by NGS to give the mean of the cancer genomics (i.e. not constrained by the genomics of a single site biopsy that may not be representative of the whole cancer). This is will occasionally be useful in directing the oncologist towards an activating oncogene that can be inhibited (the Americans say : ‘Druggable’).
Immunotherapy has an emerging role in metastatic anal cancer and this tumour may carry enough mutations to be sensitive to immunotherapy drugs such as the checkpoint inhibitors: pembrolizumab an nivolumab in particular.
NGS on the tissue biopsy of the metastases or cfDNA will inform the Oncologist as to whether the cancer has mismatch repair (MMR) deficiency (which implies that he cancer is hypermutated and likely to be antigenic enough to respond to immunotherapy).
The expression of PDL1 will also help to predict if immunotherapy will cause a response in this metastatic disease as the PDL1 expression , if high, predicts that cancer cell expression of PDL1 is preventing the immune attack on the cancer and that either a PD1 or PDL1 inhibitor may release the immune attack and cause a remission of the metastatic cancer. Immunotherapy has yet to be proven for this type of cancer.
P N Plowman MD, The Oncology Clinic, 20 Harley Street, London W1G 9PH. (Advanced Genomics).
Outcomes: The majority of patients with early anal cancer are cured with intact anorectal function (i.e. no incontinence and a fairly normally functioning ano-rectum). For those who later relapse, there is more hope than a decade ago for a durable remission.
There is no routine screening programme for this disease which is rare.
All solid lumps developing in this region should be regarded with suspicion.
Although the majority of lesions will be either haemorrhoidal in origin or painful fissures, neither of which should have a solid lump component.
Questions & answers about anal cancer
The 68 year-old female patient was diadnosed with Squamous cell carcinoma of the anus. T1 N0 M0.
Received combined chemotherapy and radiotherapy for carcinoma of the anus. Subsequent MRI and CT scans negative. Nuclear bone scan negative. Anal bleeding continued. Biopsy under anaesthetic was positive for local recurrence of anal cancer Squamous cell with Basaloid features.
The surgeon has indicated that abdominoperineal resection is likely to be offered for recurrent Anal Cancer. Can a less radical treatment be recommended with a similar success rate?
The standard first treatment for anal cancer is chemo/radiotherapy and is largely successful in eradicating the tumour whilst not causing unacceptable side effects in the majority. The dose of radiotherapy that is given at the initial treatment is as high as possible and limited by what the normal tissues can tolerate. If further radiotherapy is given by external beam techniques, the dose will have to exceed what the normal tissues can recover from and lead to permanent damage in the long term. The main concern in anal cancer is the function of the anal sphincter, which, if damaged, by too high a dose of radiotherapy can lead to permanent incontinence.
Brachytherapy is a method of delivering a dose of radiotherapy to a small volume of tumour whilst keeping the dose to adjacent structures safe. Thin tubes are placed directly into the tumour under general anaesthetic, and left in place for up to 7 days. Thin wires that are radioactive are then placed in these tubes, either for a few minutes once or twice a day, or for the full 7 days. However, there are limitations to brachytherapy: whether this treatment is safe depends on whether the tumour is within or very close to the sphincter and/or lower part of the bowel. The judgement can be made from current scans to looking at the site of the current disease relative to the tissues that received a high dose in the past. This decision can be made by the clinical oncologist/radiotherapist that works in the same team as the surgeon.
Cyberknife has a similar ethos, i.e. delivering a high dose of radiotherapy to a small region whilst limiting the dose to adjacent structures. The same limitations as brachytherapy apply.
The probability of re-irradiation curing the tumour is low whilst it is likely to cause long term side effects that are likely to require surgery to control it in the future. The chances of surgery curing the tumour are very high and is the standard, tried and tested therapy for recurrent anal cancer disease. Surgery is therefore the recommended treatment.