In the latest part of their series on cancer, Macmillan experts look at the early diagnosis, treatment and palliative care of patients with colorectal cancer


Drs Anthony Cunliffe, David Plume, Jackie Dominey, Cathy Burton, Steven Beaven, Macmillan Cancer Support GP Advisers 
Mr John Griffith, Consultant Colorectal Surgeon, Consultant Adviser to Macmillan Cancer Support 

Colorectal cancer is the fourth most common cancer in the UK, but the second most common cause of cancer death.1 Its incidence is strongly related to age and in the UK is increasing. Overall five-year survival rate is around 50%, but when detected at the earliest stage (Dukes A) this rises to around 93%. Currently fewer than 9% of cases in the UK are diagnosed at this stage. A similar percentage is diagnosed with late stage disease (Dukes D) with five-year survival of less than 7%.2 About 25% of bowel cancers present as emergencies, with obstruction or severe anaemia. These patients have higher mortality than those diagnosed as nonemergencies, so there is a considerable challenge to both primary and secondary care to achieve earlier diagnoses. The majority of colorectal cancers are adenocarcinomas, but the colon can be affected by squamous cell cancer, carcinoid tumours, sarcomas and primary lymphoma although these are all rare.3

Early detection of colorectal cancer

Achieving earlier diagnosis depends on public awareness of symptoms and signs of the disease, recognition of these in primary care and the availability of appropriate timely investigations. There are also two screening programmes – faecal occult blood (FOB) testing and flexible sigmoidoscopy – which aim to diagnose colorectal cancer at the earliest stage.

Public awareness

In the UK, public awareness of the signs and symptoms of bowel cancer is low.4 To improve this, 2012’s Be Clear on Cancer campaign encouraged people to see their GP if they had had ‘looser stools’ or ‘blood in their poo’ for more than three weeks. This led to an increase in both urgent and non urgent referrals, especially in those over 50.5

Screening 

Test kits for faecal occult blood (FOB) screening are sent to patients in England, Northern Ireland and Wales every two years from age 60-74 and from 50-74 in Scotland. Pilots of the more sensitive faecal immunochemical test (FIT) may lead to it replacing the guaiac FOB (gFOB) test. Flexible sigmoidoscopy screening involves an invitation for a one-off sigmoidoscopy at the age of 55.

Pilots began in 2013 and it is currently being introduced in England. Pilots offering it to 60 year olds have started in Scotland. An added benefit of this screening, as well as diagnosing cancer earlier, is the prevention of cancer by identification and removal of adenomas.

The role of primary care 

Suspected cancer guidelines 

Many patients with colorectal cancer never met the 2005 NICE criteria.6 Significant changes in the 2015 guidelines include age referral criteria, the introduction of abdominal pain as a significant symptom, the removal of specified levels of haemoglobin associated with iron deficiency anaemia and recognition of significance of any changes in bowel habit. A new recommendation is for FOB testing for certain symptomatic groups.

Macmillan Cancer Support has produced an updated Rapid Referral Toolkit,7 condensing the new NICE guidance into a user friendly format so that GPs can refer to it quickly in practice. The colorectal guidelines are summarised in the table on the following page.

The new guidelines, advising referral at a cancer risk of 3% compared to 5% in the previous guidelines, should lead to an increased proportion of colorectal cancers diagnosed at an earlier stage. However, implementation of the guidelines will require a greater number of referrals for diagnostic testing, increasing demands on secondary care capacity and funding. A higher proportion of patients being referred will turn out not to have cancer and should both be counselled initially and followed up in primary care to manage ongoing symptoms. We can use this “teachable moment” to advise the patient on relevant risk factors and lifestyle changes.

Co-morbidities may affect both the opportunities for treatment of cancer and the risks of developing significant side-effects or toxicities following treatment. GPs can minimise these risks by ensuring optimal management of co-morbidities and including relevant information on the two week referral form. 

Cancer decision support tools 

Cancer decision support tools, derived from research conducted by Professors Willie Hamilton in Exeter and Julia Hippisley-Cox in Nottingham about how patients with cancer present in primary care, are available.

The electronic Cancer Decision Support tool (eCDS) developed by Macmillan Cancer Support, currently available to practices using BMJ Informatica software, will soon be incorporated into the clinical systems of the major UK clinical software companies (EMIS, INPS Vision and SystmOne). This tool enable GPs to assess cancer risk in a way not previously possible.

Diagnosis 

Most colorectal cancers are diagnosed by colonoscopy with biopsies. If the entire colon has not been examined, completion CT colonography should be performed. A staging CT scan of the chest, abdomen and pelvis should be performed on all patients. Patients with rectal cancer should have an MRI scan; if the cancer has penetrated the muscularis mucosa or threatens the surgical resection margin, neo-adjuvant chemo-radiotherapy prior to surgery may be offered.

Treatment 

All patients should have treatment decisions made at the colorectal multidisciplinary team meeting. Laparoscopic surgery, which achieves comparable outcomes to open surgery5 with reduced perioperatiove morbidity, should be offered unless there are contraindications, which include locally advanced disease, low rectal cancers, previous abdominal surgery or central obesity. These are not absolute contraindications and the multidisciplinary team should seek to maximise the patient’s chances of a laparoscopic approach.

Fitness for surgery should be assessed by a consultant-based pre-assessment with cardio pulmonary exercise (CPEX) testing, helping to identify those patients who may need peri-operative intensive or high dependency care. All patients should be managed on an enhanced recovery programme to facilitate rapid, uneventful recovery from surgery. This encourages same day admission, reduced use of oral bowel preparation, early post-operative mobilisation and reintroduction of eating, and reduced length of hospital stay.

The aim of colorectal surgery is complete resection of the primary tumour with clear resection margins and the capture of as many draining lymph nodes as possible, while avoiding a permanent stoma. The latter is not always possible in patients with low rectal cancer. Right sided colonic resections have lower risks of anastomotic leaks. In left sided resections the descending colon is usually joined to the upper rectum at least 5cm below the primary tumour. This join, which is technically more difficult due to its location, is associated with a slightly greater risk of leakage, but does not necessitate a defunctioning stoma.

Rectal cancer surgery is technically more demanding, especially in male patients due to the relatively narrow pelvis. Low cancers may require an abdomino-perineal excision of the rectum and anal canal with a permanent colostomy, and many of these patients will have required chemo-radiotherapy prior to surgery, which may delay perineal wound healing.

In patients with cancer more than 5cm above the anal verge, it should be technically possible to perform an anastomosis of the descending colon to the rectal stump or top of the anal canal. When this is close to the anal verge there is a significant chance of anastomotic leakage and a defunctioning loop ileostomy may be carried out to reduce this risk.

Most patients stay in hospital for about five days after uncomplicated laparoscopic surgery, but slightly longer after open procedures or lower rectal surgery. Patients are discussed with the results of their pathology at the multidisciplinary team meeting.

Those with adverse features, such as nodal or vascular invasion, may, if well enough, be offered adjuvant chemotherapy. This may reduce the risk of cancer recurrence by 10%. For those with a defunctioning stoma, chemotherapy would delay closure.

In the unusual case where a rectal cancer has been removed and there is cancer at the resection margin, post-operative radiotherapy may be offered. If, however, pre-operative radiotherapy has been given this is not an option.

Follow-up 

The risk of recurrence is governed by the stage of the primary and the follow up regime should be stratified accordingly. For patients fit to undergo additional treatments, which now include palliative chemotherapy and resection of isolated hepatic or pulmonary metastases with curative potential, structured followup including at least two CT scans and a surveillance colonoscopy within the first three years should be offered. This may be supplemented by six-monthly CEA blood tests, which can be continued for five years.

Survivorship and consequences of treatment 

The late effects from cancer treatment and their prompt identification and treatment, are of increasing significance to both patients and GPs, as more than 65% of patients are now living for two or more years after their diagnosis.

Post-operatively, while most patients have fairly normal bowel function, defecating once or twice daily, problems with faecal urgency, frequency, incontinence or incomplete evacuation due to the removal of the rectal reservoir may occur. This is usually most marked in the early post-operative period and tends to improve over the first 12 months; if persistent, an expert opinion may be required.

Surgical treatment can also lead to urinary incontinence and sexual dysfunction. A stoma may cause both physical and psychological problems.

Radiotherapy, most frequently used for more distal colorectal tumours, can cause bowel, bladder and bone effects that may be seen during treatment or months to years later, and hence may seemingly present de-novo to us in primary care.

Pelvic radiotherapy may cause devastating gastrointestinal symptoms such as intractable diarrhoea, faecal incontinence or rectal bleeding. Patients who are wakened by the need to defecate, have troublesome urgency and/or faecal leakage, soiling or incontinence, or whose symptoms impact on their quality of life, need referral back to secondary care. Patients are commonly reluctant to raise the symptoms. Recording of pelvic radiotherapy in GP records enables the GP to be able to ask about relevant symptoms and offer support and treatment. Patient information is available from Macmillan about late effects of pelvic radiotherapy.9 Practical help, such as Macmillan’s Toilet Card10 or Disability Rights UK’s RADAR key,11 which can be purchased by those with a disability to access locked public toilets fitted with National Key Scheme locks, can prove invaluable and transform patients’ activities.

Late effects 

Late effects, which may occur years after treatment, make it important that we accurately code the treatment a patient has received in primary care records, so that we and our colleagues can make the linkage quickly between the treatment and these late effects.

Chemotherapy used in colorectal cancer can cause a variety of late effects including heart failure, venous thromboembolism, hypertension, cardiac ischaemia and peripheral neuropathy. Patient information about heart health in relation to cancer and its treatment is available from Macmillan.12 Chemotherapy in general has been linked to an increased incidence of impairment of cognition.13

Colorectal cancer patients have been shown to have significantly greater levels of depression than the general population.14 

Second primary cancers are more likely to occur in cancer survivors. This may be because of a genetic predisposition to cancers, lifestyle factors or late effects of radiotherapy or chemotherapies. Those who develop new gastrointestinal symptoms more than five years after radiotherapy need referral to exclude a second malignancy.15 

End of life care 

General principles 

As a patient enters the end of life stage of their illness, oral medication should be rationalised, as priorities change and absorption may become unpredictable. Some symptoms are especially likely to occur in patients dying from colorectal cancers.

Intestinal symptoms 

Diarrhoea may be diminished by loperamide (max. 16mg daily) or codeine phosphate (max. 240mg daily), both acting to reduce peristalsis and increase sphincter tone, but patients should be warned of the risk of constipation with overflow diarrhoea.

Constipation is particularly likely to occur in those taking opiods. Use of osmotic laxatives such as lactulose and movicol should be avoided when fluid intake is low, as abdominal distension and colic is more likely in these situations. Docusate acts as a stool softener (dosage up to 600mg daily) and is usually well tolerated in capsule form, although the liquid tastes unpleasant. Senna is an appropriate stimulant when needed.

Fistulae, rectal discharge and bleeding These symptoms may be a sign of recurrent as well as locally advanced disease and can cause significant peri-anal skin problems. Radiotherapy can sometimes be helpful even where the patient is frail, and discussion with an oncologist regarding possible treatment should be considered.

Stomas 

With weight loss, changes in a stoma may need the advice of specialist nurses. Use of creams, such as cavilon and sudocrem, both at the stoma site and perianally, can be a useful measure.

Bowel obstruction

With advanced disease, patients may experience episodes of acute or sub-acute bowel obstruction. For those not fit for consideration of palliative surgery (including stent insertion) subcutaneous hyoscine butylbromide (buscopan) via syringe driver can reduce intestinal secretions and symptoms. If ineffective after 48 hours, consider changing to octreotide by subcutaneous infusion, but unless experienced in the use of this drug, it is appropriate to discuss this with the specialist palliative care team first. Subcutaneous steroids (dexamethasone) to reduce inflammation and oedema of the bowel wall, in addition to a prokinetic (metoclopramide) may be used with caution to treat sub-acute obstruction. However, there is a risk of progressively worsening symptoms as the disease advances and the patient should be kept under regular review.

Vomiting 

Where bowel obstruction is high, vomiting will commonly be troublesome. A naso-gastric tube can sometimes give striking relief, but may not be tolerated. Anti-emetics, such as cyclizine and levomepromazine, can be effective. Prokinetics, such as Metoclopramide, are effective where vomiting is the result of squashed stomach syndrome and delayed gastric emptying due to liver enlargement with metastases. Avoid using multiple anti-emetics and, in particular, avoid the use of cyclizine with pro-kinetics as it competitively blocks the effects of metoclopramide.

Pain 

The principles of pain management in colorectal cancer are the same as other cancers, using the WHO analgesic ladder, starting with simple analgesics and moving on to strong opioids if required. However, there are some pain problems that are particularly likely to occur in colorectal cancer.

In advanced disease, pain may be caused by local invasion or bowel obstruction. Liver metastases are relatively common, causing capsular pain which often responds well to NSAIDs and/or dexamethasone. Proton pump inhibitor cover should be considered.Dexamethasone should be commenced at 8-12mg daily, either orally or sub-cutaneously, and stopped after five days if ineffective. If steroids are helpful the dose should be reviewed and reduced every five days to the lowest tolerated dose. Prolonged use of steroids can lead to additional problems including proximal myopathy and blood sugar disturbances.

Anorexia 

Malabsorption and anorexia leading to poor nutritional status will contribute to low protein levels and anaemia with resulting peripheral oedema and fatigue. Sensitive communication is needed with the patient and their carers to avoid the distress caused by well-intentioned attempts to ‘build up’ by using rich foods and sip feeds that are often unpalatable and rarely, if ever, beneficial to the patient with advanced malignancy.

Conclusion 

The increasing incidence of colorectal cancer, benefits of earlier diagnosis but continued patient presentation with advanced disease, mean that GPs have an important role at all stages in this disease. Public awareness campaigns, improved screening programmes and implementation of new guidelines may lead to improved survival. GPs will then have larger numbers of patients for whom support will be required with consequences of their treatment. 


References 

1. https://www.beatingbowelcancer.org/facts-andfigures?gclid=CIOSjJjIo8cCFY_JtAodDgQLSQ
2. http://www.ncin.org.uk/publications/data_briefings/colorectal_cancer_survival_by_stage
3. http://www.cancerresearchuk.org/about-cancer/type/bowelcancer/about/types-of-bowel-cancer
4. http://www.sciencedirect.com/science/article/pii/S0091743503000161
5. http://www.cancerresearchuk.org/health-professional/early-diagnosis-activities/be-clear-on-cancer/bowel-cancercampaign/evaluation
6. BMJ 2013;346:f3172
7. www.macmillan.org.uk/Documents?AboutUS/Health_professionals/PCCL/Rapidreferralguidelines
8. Bonner et al, A randomized trial of laparoscopic versus open surgery for rectal cancer. NEJM, 2015
9. http://www.macmillan.org.uk/information-and-support/coping/side-effects-and-symptoms/late-effects-pelvicradiotherapy
10. http://be.macmillan.org.uk/be/p-22494-toilet-card-pelvicradiotherapy.aspx
11. http://disabilityrightsuk.org
12. http://be.macmillan.org.uk/Downloads/CancerInformation/LivingWithAndAfterCancer/MAC14637Hearthealthandcancertreatment2014.pdf
13. BJC 2011;105:329
14. Lancet Psychiatry 2014;1(5):343-350
15. GUT 2012;61(2):179-92