Association of Coloproctology of Great Britain &amp; Ireland (<scp>ACPGBI</scp>): Guidelines for the Management of Cancer of the Colon, Rectum and Anus (2017) – Diagnosis, Investigations and Screening

Abstract

Investigation of colorectal cancer may be considered in three distinct groups: Concern over a diagnosis of colorectal cancer should prompt urgent referral, in most cases within general practice through a ‘two week wait rule’. Criteria for two-week wait referral (National Institute for Health and Clinical Excellence, 2015) should be satisfied and in many institutions, patients are offered a ‘direct to test service’. Initial investigations are planned on the basis of presenting symptoms (anaemia, change in bowel habit, rectal or abdominal mass), age and co-morbidity, as well as available local expertise and resources. A typical investigation algorithm is shown in Table 2.1. Patients presenting via a non-urgent route should also be investigated along similar lines. The NICE guidance (NG 12) for suspected colorectal cancer (National Institute for Health and Clinical Excellence, 2015) recommends using faecal occult blood testing for a subset of patients without rectal bleeding. This remains contentious due to equivocal evidence in symptomatic patients. Its practical implementation remains challenging in most regions. Colonoscopy Fit for bowel prep?* Y { } N { } Positive test (cancer) – direct referral to MDT via colorectal nurse specialists Or to other MDT if non-GI cancer e.g. ovarian Negative test (no major pathology) – Once cancer has been excluded, patient will be referred back to GP e.g. coeliac disease, gallstones, hernias etc. Only in exceptional circumstances where immediate onward referral is deemed clinically necessary will onward referral be made by the secondary care clinician see OTHER below: Other - Any condition detected on investigation that poses imminent danger of deterioration or serious harm to the patient e.g. AAA >5 cm, Inflammatory bowel disease, decompensated cirrhosis, colonic polyp ≥1 cm, will be referred directly to the appropriate service. Colonoscopy Fit for bowel prep?* Y { } N { } No change in bowel habit Rectal bleeding persistently for >6 weeks without a change in bowel habit & without anal symptoms CT colonography or colonoscopy CT colonography or colonoscopy + OGD CT colonography or colonoscopy + OGD Patients with suspected colorectal cancer should be referred urgently to a team specializing in the management of colorectal cancer. Recommendation grade D The recent UK Special Interest Group in Gastrointestinal and Abdominal Radiology (SIGGAR) trials (Atkin et al., 2013; Halligan et al., 2013) provides level I evidence on the choice for whole colon imaging in patients with symptoms suggestive of colorectal cancer. The trial comprised a composite single endpoint incorporating: The principal finding was that CTC detected significantly more cancers and large polyps than DCBE (7.3% vs 5.6%; P = 0.039). Patients randomized to CTC were diagnosed with fewer post-test colorectal cancers than DCBE during a 3-year follow up period (3/45 vs 12/85). No significant difference was found in detection rates between CTC and OC (10.7% vs 11.4%) but CTC generated more colonic investigations than OC (relative risk 3.65). Post-test colorectal cancers during 3-year follow up were 1/29 for CTC and 0/55 for OC, confirming prior meta-analysis suggesting no significant difference in sensitivity of the two tests for colorectal cancer (Pickhardt et al., 2011). Patients with suspected colorectal cancer should be offered either optical colonoscopy or CT colonography. Recommendation grade A CT colonography should replace double contrast barium enema. Recommendation grade A Regardless of whether OC or CTC is used, certain levels of Quality Assurance should be achieved by these investigations. Colonoscopy should be performed by an experienced colonoscopist, or a colonoscopist who has been certified by the Joint Advisory Group (JAG), or by trainees supervised by one of the above. National quality and safety standards for endoscopy have been set by the Department of Health using a Global Rating Scale (GRS) (www.grs.nhs.uk) and by the British Society for Gastroenterology (www.BSG.org.uk). The quality and safety indicators underpin the respective items using GRS. There are several international consensus recommendations regarding acquisition of CTC images (Burling, 2010; McFarland et al., 2009; Neri et al., 2013). The examination may be performed following full purgative bowel preparation and administration of a faecal tagging agent (oral contrast medium administered several hours prior to the investigation). Some faecal tagging agents such as sodium amidotrizoate/meglumine amidotrizoate (Gastrografin) also have a laxative effect and can be used as a combined cleansing/tagging agent. Although some oral faecal tagging agents have a laxative effect, others do not, and in particularly frail patients a combination of dietary manipulation and non-laxative faecal tagging (such as low-dose iso-osmolar iodinated contrast media, or certain barium sulphate preparations) may achieve adequate image quality to exclude clinically relevant neoplasia. In all cases (with or without purgation), faecal tagging is now regarded as mandatory when performing CTC. Mechanical insufflation with CO2 reduces patient discomfort and improves colonic distension, when compared with room air. Intravenous antispasmodic, typically hyoscine butylbromide (Buscopan), also improves distension and may reduce pain. The use of intravenous contrast medium is not essential for colonic lesion detection, but may be an efficient strategy in patients in whom the pre-test probability of either colorectal cancer or important extracolonic pathology is high, and is invariably given when whole colon imaging and staging is required following detection of a cancer where OC failed to evaluate the proximal colon. All reporting radiologists must meet the recommended standards for competency, and be actively involved in audit of their practice and performance (British Society of Gastrointestinal and Abdominal Radiology (BSGAR), The Royal College of Radiologists, 2014). There are specific stipulations for radiologists involved in the National Bowel Cancer Screening Program (NHS Bowel Cancer Screening Programme, 2012). Radiological and endoscopic investigations should meet national standards and be subjected to regular Quality Assurance. Recommendation grade C Colon cancer should ideally be confirmed histologically, but when a lesion with high probability of malignancy has been detected by CTC, histology prior to surgery is not essential if the segment cannot be reached endoscopically. Conversely, histological confirmation of malignancy should be considered mandatory in all rectal cancers when surgery might result in either a permanent stoma or an ultra-low anterior resection, or when neoadjuvant therapy is being considered. Exception to this may be a large endoluminal lesion where biopsies have been inconclusive and the lesion is not amenable to endoscopic surgery. Preoperative histological confirmation of colonic cancer is desirable but not essential in cases with high probability of malignancy based on clinical presentation and optimal imaging. Recommendation grade D Pre-treatment histological confirmation of rectal cancer is considered essential. Exceptions should be rare and are usually large lesions not amenable to endoscopic removal and inconclusive biopsies. Recommendation grade D Local extent of colonic disease is assessed by abdominal and pelvic computed tomography (CT) to provide information on extent of spread in relation to the bowel wall and adjacent organs. This is essential to the planning of surgery (e.g. non-anatomical resection) and to allow consideration of neoadjuvant therapy when the disease is locally very advanced or unresectable. CT has limited ability to differentiate the individual layers of the bowel wall, making the distinction between T1 and T2 disease challenging. Although certain tumour morphology features seen on CT colonography, namely an arc-shaped or trapezoidal tumour configuration, may suggest T1 or T2 status, these are yet to be validated in a prospective, multicentre setting. Similarly, the distinction between T3 and T4 disease can be challenging because the latter may be contingent only on sub-millimetre spread through the serosa for peritonealised colon (T4a by TNM 7th edition; T4b by TNM 5th edition). Conversely, because of the naturally high contrast at CT between the bowel wall and the adjacent fat, T3 disease can usually be discriminated from earlier-stage lesions, with one meta-analysis suggesting a 86% sensitivity for T3 disease (Dighe et al., 2010). Furthermore, CT provides potentially useful preoperative prognostic information; tumours can be reliably split into ‘low-risk’ and ‘high-risk’ subgroups depending on depth of transmural spread and local lymph node status (Smith et al., 2007). However, at present there is insufficient evidence to recommend triage of higher risk patients for neoadjuvant treatment on these grounds alone, pending the results of ongoing clinical trials such as FOxTROT (EudraCT 2007-001987-55). FOxTROT will also provide information on the accuracy of CT in the straight to surgery arm (Foxtrot Collaborative Group, 2012). Lymph node staging is more challenging, although in most cases involved nodes lie along the local vascular pedicle, which is removed with the primary. Meta-analysis suggests that CT is approximately 70% sensitive for the detection of nodal involvement for colonic cancers (Dighe et al., 2010), similar to prior meta-analysis for rectal cancers. Magnetic resonance imaging (MRI), with few exceptions such as patients with contra-indications to MRI or unwilling due to phobia, is recommended for local staging of rectal cancers, particularly to determine the risk of the circumferential margin (CRM) being involved or threatened by tumour. The ability of MRI to predict a clear (>1 mm) CRM in rectal cancer is very good (>90%) (MERCURY Study Group, 2006). However, staging of lymph nodes is less accurate. Cancers of the lower third of the rectum are defined on MRI as an adenocarcinoma with its lower edge, at or below the level of origin of the levator muscle on the pelvic side-wall (Moran 2014). Patients with low rectal cancers have generally worse outcomes in terms of curative (R0) resection, local recurrence and overall survival compared to mid and upper rectal cancers. Specific management issues have been identified and addressed through the LOREC program, in order to try to improve outcomes in this group. Rectal cancer requires specifically tailored locoregional staging since this affects the feasibility and timing of radical surgery, and this will be discussed further in Chapter 4. Since introduction of the UK NHS Bowel Cancer Screening Program, increasing numbers of early colon and rectal cancers are being diagnosed. Suspected early stage rectal cancers should be assessed with endorectal ultrasound for more accurate local staging if considering the patient for an organ preserving approach. A Significant Polyp Early Colorectal Cancer (SPECC) Program is currently underway to improve definition, recognition, documentation, strategic planning and treatment of these lesions (Pelicancancer.org.uk). Colorectal cancers commonly metastasize to the liver, lungs and peritoneum. Routine staging by CT chest, abdomen and pelvis provides adequate staging in most cases. Further characterization of equivocal liver lesions may be assisted by MRI. 18-Fluorodeoxyglucose positron emission tomography/CT (18-FDG PET/CT) may be used to investigate suspicious lesions seen on CT or MRI. In addition, PET/CT provides valuable assessment to help exclude occult metastatic disease in patients being considered for non-anatomical resection of locally advanced cancers or surgical management of liver and lung metastases, to facilitate appropriate patient selection aiming to reduce futile procedures (Adams et al., 2013). Synchronous colorectal cancers are present in 2–3% of patients and a further 20% have synchronous significant benign lesions (diverticular disease, colitis or polyps). Synchronous lesions should be diagnosed at colonoscopy or CTC, as this is crucial in planning complete surgical resection. The most distal significant lesion in the colon should be tattooed (Williams et al., 2013) with the proviso that the endoscopist should ensure they are in the sigmoid and not the rectum. The tattoo should be placed into a saline bleb 2–5 cm from the base of the lesion on the distal (anal) side and the estimated distance clearly documented. More than one tattoo may be applied but the endoscopist should document very carefully the number and position of tattoos in relation to the polyp or tumour. Rectal lesions should not be tattooed. All patients with suspected colonic cancer should be staged with a CT thorax, abdomen and pelvis. Recommendation grade B All patients with suspected rectal cancer should be staged with a CT thorax, abdomen and pelvis. Patients being considered for curative locoregional treatment should have MRI of the pelvis. Recommendation grade B Synchronous lesions should be identified using colonoscopy or CTC prior to colorectal cancer resection. If complete colonoscopy is not possible, CTC should be considered. CT of the thorax can be combined with CTC to permit staging at the same hospital visit. Recommendation grade B The NHS BCSP offers screening every 2 years to the population aged between 60–69, as over 80% of newly diagnosed colorectal cancers occur at this age and beyond. Since 2008, the screening age group has been extended to 74 years old, in accordance with the government's strategy to improve cancer outcomes. Screening with guaiac faecal occult blood test (FOBT) has been shown to reduce colorectal cancer mortality in four large population-based randomized control trials after more than 10 years of follow up (Table 2.2) (Hewitson et al., 2008). The results from the UK and Denmark were directly comparable. The apparently superior results in the US trial were ascribed to a far higher colonoscopy rate, which in turn was due to more frequent FOB testing and a lower positive test threshold. The guaiac FOBT is being replaced with the more accurate faecal immunochemical test (FIT) for colorectal cancer screening programs (Halloran et al., 2012). It has shown improved uptake and the ability to detect significantly more colorectal cancers and advanced adenomas (Digby et al., 2017; Moss et al., 2016). However, the higher uptake and test positivity is likely to stretch colonoscopy services even further (Tinmouth et al., 2015). People with positive faecal occult blood tests (5 or 6 samples tested positive; or 1–4 samples positive, followed by any positive result on two subsequent screening kits) are offered a screening colonoscopy. This is carried out in endoscopy units by a JAG accredited BCSP colonoscopist. For individuals unwilling to have or who cannot tolerate colonoscopy, CTC could be considered. Follow up colonoscopies will be determined by the results of the index colonoscopy. The NHS BCSP has had a positive impact on elective treatment of colorectal cancers by early cancer detection, increased use of minimally invasive techniques and reducing the need for emergency colorectal cancer resections. It also has had a positive impact on 30-day postoperative mortality and 5-year survival rates. A randomized controlled trial in the UK has shown that a ‘one-off’ screening flexible sigmoidoscopy reduces CRC incidence and CRC-related mortality by 23% and 31% respectively (Atkin et al., 2010) after a median follow up of 11 years. Results from the UK trial have prompted the NHS to roll out a population-based program using flexible sigmoidoscopy as screening offered at age 55 with the option to opt in up to aged 60 (http://www.cancerscreening.nhs.uk/bowel/). Population-based NHS Bowel Cancer Screening Program will increase detection of early stage disease, improve cancer survival and reduce the need for emergency surgery. Establishment of flexible sigmoidoscopy screening is likely to reduce incidence of distal cancers as well as reducing mortality. Recommendation grade A Patients diagnosed through the National Bowel Cancer Screening Program should have a defined pathway into their local colorectal cancer MDT. Recommendation grade D Approximately 5% of colorectal cancers are due to the high-risk familial conditions, Lynch syndrome and the polyposis syndromes. It is important that these familial syndromes are identified so that the index case and family members can be offered appropriate management. In a further 30% there is some familial contribution to aetiology, but the genetic factors involved remain unclear and the level of risk is heterogeneous. Families deemed to be at high risk of colorectal cancer should be managed through clinical genetic services, which should provide a robust program appropriate use of genetic and accurate family an assessment of The and age at diagnosis of all cancers in family members should be as well as the of features such as colorectal The of risk assessment on the basis of family is limited in and with defined et al., 2010) a evidence base for risk level to family and provide screening recommendations in Table risk in this group have one of the risk individuals should be of the symptoms of colorectal cancer and to in the NHS Bowel Cancer Screening Recommendation grade C risk This group with one risk individuals should be offered a ‘one-off’ screening colonoscopy at the age of 55 years. Recommendation grade C risk risk individuals should be offered colonoscopy every years from the age of to years. Recommendation grade C risk This Lynch syndrome and the polyposis syndromes. Criteria for This condition is due to in one of the and a risk of colorectal cancer at an early as well as increased incidence of other cancers. The cancers are by and of by There is a of and cancers compared to colorectal cancer for testing are increasing with recent evidence its use in all patients with colorectal cancer et al., 2013). Further of status and can cases of from with a genetic for the management of individuals with Lynch syndrome are available et al., and suspected of should be referred to a clinical for the clinician these patients for Lynch syndrome should at the age of years and for every up to the age of years or clinically Recommendation grade B In cancer as of the upper endoscopy should be considered from age of years and to age years. Recommendation grade C This syndrome is by the of of colorectal adenomas from and results in a risk of colorectal cancer by the age of years. In 20% of patient with the genetic from a The most important are and adenomas and and for the management of individuals with are available et al., and suspected of should be referred to a clinical or polyposis for the clinician these patients colonoscopy should be offered to from diagnosis polyp a need for surgery. Recommendation grade B from where no can be identified and genetic is not possible, should have from the age of age and every years age Recommendation grade B For individuals who have either and or and endoscopic of the rectum or is Recommendation grade B endoscopy a at determined by stage for is recommended from age years. Recommendation grade C This polyposis syndrome has with although the polyp is and are less frequent et al., 2010). of the colon and rectum is the same as although some individuals with a polyp can be managed without the need for surgery. is recommended every from age years for individuals who are of other Recommendation grade C endoscopy at is recommended from age years. Recommendation grade C This condition is by the of polyps and adenomas et al., 2013). There to be an but the have not yet been identified and genetic testing is not colonoscopy is should have screening from the age of years. Recommendation grade C This syndrome results in particularly in the and et al., 2010). The risk of and other cancers, is patients should be referred to a clinical or polyposis A colonoscopy and upper endoscopy is recommended at age years. If significant polyps are endoscopy should be every years. If no significant polyps are present at is at age or should symptoms and every years. Recommendation grade C bowel screening using endoscopy should be performed every from age or if the patient is Magnetic resonance or CT are in patients but CT is not in due to Recommendation grade C This is a rare syndrome due to in the or which results in typical particularly in the large bowel et al., 2010). The risk of colorectal cancer is in the and that of cancer is usually by endoscopic with of depending on polyp or is with a also have so bleeding or may not be due to the and appropriate investigations to exclude should be any general patients should be referred to a clinical or polyposis for at risk individuals and is recommended every years from age or if the individual is symptomatic up to age years. Recommendation grade C is recommended every years from age years. Recommendation grade C of the have any of to is a National Institute for Health and is by at the