Key learning points:
– Colorectal cancer is the third most common cancer and second biggest killer in the UK, however, if it’s found early there is a 95% cure rate
– Any patient with a change in bowel habit for more than three weeks, rectal bleeding with no obvious cause, anaemia or a palpable mass should be referred for investigation no matter the age
– The treatment options for colorectal cancer have changed dramatically in the past five years, though surgery is still seen as the definitive treatment
Colorectal cancer is the third most common cancer in both men and women and accounted for 41,581 cases in the UK in 2011.1 If diagnosed at an early stage there is a 95% cure rate, yet it is the second biggest killer in the UK as patients often present with advanced disease.1 There has been a substantial improvement in survival with almost six-in-10 bowel cancer patients surviving 10 years.1 It is still most common in the over 65 age group. Although, there has been a significant increase in those under 50 year of age in the past decade, with a predicted increase in the 20-34 year old age group of 90% for colon and 124% for rectal cancers by 2030 and 27.7% for colon /46% for rectal cancers in the 35-49 year old age group.2
Causes
There are several risk factors believed to be linked to the development of colorectal cancer, these include a diet high-in-fat and low-in-fibre as well as high alcohol intake and a lot of red/processed meat. Smoking and lack of exercise are thought to be risk factors.3 Patients who have had ulcerative colitis or Crohns disease for more than 10 years are also thought to be at risk. There are some genetic abnormalities with links to colorectal cancer which cause the bowel to produce multiple polyps. Therefore patients with Lynch syndrome and familial adenomatosis polyposis (FAP) should be routinely screened by colonoscopy.
Signs and symptoms
Symptoms of bowel cancer are often non-specific, which is why patients often present late. Right-sided bowel cancers often present with anaemia, a change in bowel habit to looser stools and crampy abdominal pain. These tumours can grow to a fair size without spreading and can therefore be palpated. Left sided tumours are very similar in presentation but may also have per rectal (PR) bleeding and a change in bowel habit causing constipation as the bowel starts to block. However, rectal cancers tend to be more symptomatic with tenemus and feelings of incomplete evacuation as well as PR bleeding. Current guidance suggests patients more than 40 years of age with unexplained weight loss and abdominal pain and patients aged 50 and above with unexplained rectal bleeding should be referred as a two week wait referral. Patients older than 60 with iron-deficiency anaemia or a change in bowel habit for more than three weeks, or a positive faecal occult blood test (FOBT) should also be referred.4 While this will capture the majority of patients with colorectal cancer, it is important to remember this is not exclusively a disease in those aged more than 40 years of age, and any patients with these symptoms should be referred for assessment.
Diagnosis
Early diagnosis is the focus of many cancer networks within the UK, therefore, many of the referrals will ask if the patient is fit to attend a straight-to-test service. The standard investigation for colorectal cancer includes a colonoscopy and computed tomography (CT) of the chest, abdomen and pelvis. Rectal cancers will also have a magnetic resonance imaging (MRI) scan of the pelvis. A carcinoembryonic antigen (CEA) blood test is used to monitor patients during follow-up but is not specific in confirming if a cancer is present.
Surgery
Standard treatment for a bowel cancer is surgical resection. This can be done as either an open operation or laparoscopically. While the preference is laparoscopic resection, there is no difference seen in outcomes with patients entered into an enhanced recovery programme.5 Most standard resections will result in approximately 30cm of bowel being removed as well as the lymph nodes surrounding this area. In the bowel, unlike the breast, removal of the lymph nodes has no lasting effect, however, removal of the colon may result in a change in bowel habit. Stoma formation may be required with colorectal surgery, though this can be on a temporary or permanent basis. A temporary stoma is for a minimum of three months and is often not reversed until a patient completes adjuvant chemotherapy. The main complication of surgery is an anastomotic leak. This can range from a small leak requiring no intervention to the need for a laparotomy and formation of stoma. The other common risks are a chest infection, wound infection and deep vein thrombosis (DVT).
Bowel dysfunction is one of the most common side effects of treatment, with only 40% of patients returning to normal function post-surgery, and even then this can take many months to occur. The 60% who experience post-surgical dysfunction may have urgency, diarrhoea and constipation requiring medical management.6 This can occur immediately post-surgery and be a long term issue. Diarrhoea is the most common side effect and can be managed by diet alone for many patients, although some patients will require loperamide. Dietary advice should be given to patients, such as having regular meals, restricting tea and coffee to three cups per day, reducing alcohol and fizzy drinks. Additionally, limiting the intake of high fibre foods, such as wholemeal and whole grains as well as fibrous vegetables should be advised. It’s also important patients don’t drink near the time they eat because this will speed up digestion. They should ensure there is something solid with each meal, for example to have a bowl of soup with white bread as well.
Loperamide is effective at slowing the bowel transit down, although the dose needed for each patient is different.7 If a low dose causes constipation, liquid loperamide is often easier for these patients as they can titrate the dose by 1mg each time. Some patients will find this is not effective and may find codeine phosphate works better, additionally some patients may need a combination of both to gain control again. Diaries of food intake and medication are particularly useful to look at which foods affect individual patients, and the effect of the medication on the bowel.
Patients often experience increased wind post surgery. Oats, linseed and peppermint can help with this as well as reducing the intake of foods known to produce wind, for example beans and pulses. Wind can also be incredibly painful and some patients may require strong analgesia to manage this. Buscopan and colpermin can help for some patients as well as mebeverine.
Constipation can be a long-term issue for some patients post surgery and they may require long-term laxative usage. These patients should be advised to increase their fibre intake to 25g per day and to increase their fluid intake to a minimum of eight cups of fluid per day. Exercise will also help with this. Movicol is often the laxative of choice for many patients because it’s an osmotic agent and tends not to cause abdominal pain.8
Anterior resection syndrome is common post surgery where the rectum is removed or reduced in size. This presents as erratic bowel habit, tenesmus and evacuation difficulties. Often patients will have urgency to get to the toilet, and many have to go numerous times to get clearance. There are bowel retraining exercises and medication management that can help with this. It is also suggested that if conservative management fails, referral for biofeedback, percutaneous tibial nerve stimulation (PTNS) or irrigation should be considered.9 It is also thought that early intervention is better and patients can be referred from six weeks post completion of treatment.10 However, not all hospitals have access to a gastrointestinal (GI) physiology department or trained nurses in biofeedback so this may not occur for all patients.
Chronic abdominal pain can occur for some patients due to adhesions. This is difficult to manage as corrective surgery may produce more scar tissue, and medical management with analgesia may not help. It is rare for this to have a significant impact on quality of life but for some patients it can be debilitating.
Radiotherapy
Radiotherapy has limited use in colon cancer due to the effect of radiation on the small bowel, but it does have use in rectal cancer. For those who have threatened circumferential margins, radiotherapy in conjunction with capecitabine chemotherapy can be used to downstage the tumour to ensure a complete excision can occur. It is given over 25 days on weekdays with daily chemotherapy.11 Surgical resection usually occurs approximately 12 weeks post completion. During treatment, patients can experience diarrhoea, nausea and vomiting, skin alterations, pain and lethargy. These tend to be a cumulative issue and can occur for 10-14 days post completion of treatment when the radiotherapy is at its maximum dose. Short course radiation is still used pre-operatively in many centres, or for symptom management for patients who are unfit for surgery/chemo-radiation or for those with metastatic disease. This is a higher dose of radiation given daily over five days.
Patients who have undergone radiotherapy can develop late effects including change in bowel habit, PR bleeding, skin alterations, impotence in men, vaginal stenosis and cystitis. All women should be offered vaginal dilation from two to eight weeks post completion of radiotherapy to reduce the risk of stenosis, which should continue life-long.12
There are different methods of giving radiotherapy, including standard treatment and image modulated radiotherapy. For patients with a small site of recurrent disease cyberknife can also be used, which allows a high dose of radiation to be given to the tumour, but reducing the dose given to other structures in the area.
Chemotherapy
For patients with high-risk Dukes B tumours (T4 disease or extramural vascular invasion) or Dukes C tumours with nodal disease, chemotherapy is thought to reduce the risk of recurrence thought there is minimal benefit in patients over 80.13 This is usually given as a combination of oxaliplatin and a fluoropyrimidine, namely capecitabine or fluorouracil. Single agent capecitabine or fluorouracil may be used for elderly patients or those with peripheral neuropathy. This is given every two or three weeks depending on the regime and lasts for 24 weeks. The main side effects are peripheral neuropathy (which can be permanent), diarrhoea, mouth ulcers, hand/foot syndrome, fatigue and pancytopenia. It rarely causes hair loss. Many patients are able to return to work and travel while on this regime, although some who have more severe side effects may not feel able to. This chemotherapy is also used for patients who have resectable liver or lung disease in a neo-adjuvant or adjuvant setting.
Chemotherapy for patients with metastatic disease has changed dramatically with the introduction testing for KRAS, NRAS and BRAF genes and the use of anti-angiogenesis drugs and monoclonal antibodies. In addition to standard chemotherapy they allow for a personalised approach to be taken to the care of these patients. Those who are wild-type in all three genes are thought to have an increased chance of survival, which may be due to them responding to monoclonal antibodies such as cetuximab or panitumumab. Survival has now improved to an average of 33 months though many live longer.14
Treatment of liver metastases
For the best chance of a potential cure, liver resection is seen as best practice. This may be done in a single or combined procedure and can be repeated if further metastases occur due to the regrowth of the liver. Approximately 52% of patients will be disease-free in five years post surgery.15
This is not possible in all patients, therefore other treatments have been developed to control the disease. The most frequently used is ablation. This can be radiofrequency, microwave ablation or cryotherapy, and works by killing the cells locally as well as a small percentage of healthy tissue around the metastases. The current guidelines suggest that up to five tumours can be treated but these need to be under 5cm in size.16 It usually involves a one night stay in hospital after a general anaesthetic. It can cause pain and bleeding post-treatment, but is generally well tolerated and can be repeated if new disease occurs.
Drug eluding bead transarterial chemoembolization (DEB-TACE) is a localised liver treatment using irinotecan soaked beads that are inserted into the liver via the artery. It is used to control disease rather than curing, and trials suggest an 80-90% response rate to this form of treatment.17 The risks of the procedure include an abscess formation, liver damage in 5% of patients, bleeding of around 1-2%, nausea and the patient can feel tired for one week post.
Selective internal radiation therapy (SIRT) is the introduction of radiosensitive beads into the liver via the hepatic artery similar to DEB-TACE but it uses Yttrium instead.18 It is suitable for patients who have liver only disease with an expected life expectancy of greater than 12 weeks and a performance status of 0-2. It is usually done in a two-stage procedure with the first being a prophylactic occlusion of the extra hepatic artery, followed by a second procedure where the beads are inserted. The side effects are a low-grade fever, abdominal pain, nausea and abnormal liver function tests considered to only last for one week. Funding is only given for this procedure if the patient has progressed on both oxaliplatin and irinotecan based regimes.
Treatment of lung metastases
The treatment of lung metastases is similar to liver metastases in that surgical resection is thought to be the best for overall survival and is generally done via a video-assisted thoracoscopic surgery (VATS) lobectomy or segmentectomy.19 Ablation is also another treatment option for lung metastases. It is considered to a well-tolerated and can be repeated if required.
Radiotherapy can also be used, although it is not as commonly used in colorectal cancer and tends to be for symptom control only eg, for haemoptysis.
Psychological impact
As with any cancer the psychological impact of having colorectal cancer differs with each patient but often patients experience shock, anger, guilt and anxiety. They can at times be withdrawn and feel isolated from their family and friends or work, which may stem from the feeling of a loss of control. Once in follow-up they have to deal with the uncertainty of not knowing if the cancer will return and often experience anxiety – particularly around follow-up scans -which may not improve even when they attend their final scans. Support from family and/or friends is vital in helping patients manage this, as well as access to a clinical nurse specialist. While access to psychologists is still limited in the UK there are numerous other forms of support available at many hospitals. National charities such as Macmillan and Beating Bowel Cancer don’t require clinical referral but just signposting for patients to gain peer support and written information.
Conclusion
Colorectal cancer is very common but also very treatable if caught early, and for those with advanced disease it is now seen as a long-term illness with the increase in treatments and survival. The treatments however do have a long-term impact on patients. Fatigue, pain and peripheral neuropathy for those who had oxaliplatin are also issues that need to be addressed for many patients post-treatment, as well as the psychological impact of cancer. More research is needed to address these survivorship issues in the future.
References
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