Approach

Clinical evaluation

Patients with colorectal cancer present in three ways:

  • Outpatients with suspicious symptoms and signs

  • Asymptomatic individuals discovered by routine screening of average and high-risk subjects

  • Rarely, emergency admission with intestinal obstruction, peritonitis or bleeding.

All patients, regardless of age, presenting with symptoms associated with colorectal cancer, should undergo a prompt tailored evaluation for both gastrointestinal and non-gastrointestinal causes.[41] Abdominal pain, change in bowel habit, rectal bleeding, or anaemia are the most common presenting symptoms. Abdominal pain in isolation, rectal bleeding associated with anal symptoms, and change in bowel habit with harder stools, have a low predictive value for colorectal cancer. US and UK guidelines report risk thresholds for testing among low- to average-risk symptomatic populations.[41][110][111]

Left-sided colorectal cancer can present with a change in bowel habit due to a progressive narrowing of the bowel lumen, typically presenting with diarrhoea, a change in stool form (small calibre or ribbon-like stools) and, eventually, intestinal obstruction. However, the above symptoms are non-specific and can occur in other gastrointestinal conditions.

Between 6% and 10% of patients with iron-deficiency anaemia will be found to have colorectal cancer, most commonly on the right side of the colon.[3][112][113]​​

Signs and symptoms of advanced disease

Abdominal distension, weight loss, and vomiting are the less common symptoms and may indicate advanced disease.[3] Rectal pain may indicate a bulky tumour with local invasion in the pelvis. Tenesmus is frequent with rectal cancers. However, physical examination is frequently normal (other than in emergency cases) and should always include a digital rectal examination to check for a palpable lesion. In advanced disease, there may be a palpable abdominal mass or liver enlargement due to metastases.

Endoscopy

Complete examination of the colon is indicated in patients with suspected colorectal cancer.[114]

Colonoscopy

The preferred investigation, providing there is no clinical evidence of impending intestinal obstruction that would contraindicate administration of bowel preparation and insufflation of the colon.​[3][115]​ It is the most sensitive diagnostic test for colorectal cancer and allows for biopsy of suspicious lesions and removal of incidental polyps.[3]

Colonoscopy is highly operator dependent

Completion rates (i.e., scope passed to the cecum) vary substantially, and a rate of 90% is considered acceptable. Many individuals achieve rates of 98%. Incomplete colonoscopy contributes to a miss rate of 2%, and poor bowel preparation contributes to a miss rate of 6%.[116]

Other procedural risks are related to sedation and colonic perforation (up to 0.12%).[117][118]

Alternative procedures

A flexible sigmoidoscopy may be appropriate in a low-risk patient, such as a patient younger than 50 years with an isolated rectal bleed. If a cancer is detected at flexible sigmoidoscopy, it is important that complete visualisation of the whole colon is achieved either pre- or postoperatively because synchronous cancers occur in around 5% of patients.[119]​ Flexible sigmoidoscopy screening effectively reduced distal colorectal cancer incidence and mortality, compared with no screening, in one systematic review and meta-analysis[120]​ However, alone, it is not considered adequate screening for colorectal cancer.

Double-contrast barium enema is safe and well tolerated, and does not require intravenous sedation. However, patients in comparative studies preferred colonoscopy or computed tomography (CT) colonography to double-contrast barium enema for visualisation of the colon.[121][122][123][124][125] Double-contrast barium enema or CT colonography may be considered for patients who are unwilling to undergo colonoscopy, who are not suitable candidates for colonoscopy, or for whom colonoscopy is contraindicated.

Imaging studies

CT colonography (virtual colonoscopy) provides an endoluminal view of the colon similar to traditional colonoscopy. It has equal sensitivity to conventional colonoscopy for detection of colorectal cancer, and does not require sedation, but has less specificity.[114][126][127]​ CT colonography and optical colonoscopy are considered to be more sensitive tests than barium enema; patients appear to prefer CT colonography to double-contrast barium enema.[123][124][125]

CT colonography can be used to complete colonic assessment when optical colonoscopy cannot be completed due to technical reasons such as a tortuous colon or stenosis. It can also be used to assess patients who are unwilling to undergo colonoscopy, who are not suitable candidates for colonoscopy, or for whom colonoscopy is contraindicated.

Imaging may need to be combined with flexible sigmoidoscopy if the sigmoid colon is not adequately visualised (e.g., in patients with severe diverticular disease).

Equivocal test results may need further investigation.

Further imaging and histology

Colon and rectal cancer should be confirmed by histology.[115][128]

Once a diagnosis of colorectal cancer is made, further imaging is performed to stage the disease. Liver and chest imaging, usually with CT chest, abdomen, and pelvis, is necessary to detect metastases.[115]

Magnetic resonance imaging (MRI) rectal cancer protocol (or transrectal endoscopic ultrasound if MRI is contraindicated) is necessary to provide a local (T and N) stage for rectal cancers, which is then used to help direct treatment choice.[129] MRI is the preferred modality for local staging because of its accuracy for determining both circumferential resection margin and T stage of the primary tumour.[130]

Imaging studies to consider

Indications for positron emission tomography (PET) scan include detection of extrahepatic metastases in patients thought to have liver-only metastatic disease in whom surgical metastasectomy is being considered.[131][132][133]​ However, one trial found that PET-CT did not result in frequent change to surgical management compared with CT alone in patients with potentially resectable liver metastases.[134]

PET may help to identify recurrence in patients in whom this is suspected on the basis of symptoms or a rising carcinoembryonic antigen, but in whom the diagnostic work-up is negative.[135][136][137]

Laboratory investigations

Routine full blood count, liver biochemistry, bone profile, and renal function are recommended baseline tests.

Quantitative faecal immunochemical test (FIT)

Small amounts of blood in faeces, which indicates possible colorectal cancer, is detected by FIT.[111][138]​​​ The UK guidelines recommend offering FIT in primary care settings to detect people likely to have colorectal cancer, so as to prioritise them for referral to secondary care.[111][138] FIT Symptomatic Opens in new window​ Quantitative FIT using HM‑JACKarc or OC‑Sensor to guide referral for suspected colorectal cancer is recommended in adults:

  • with an abdominal mass, or

  • with a change in bowel habit, or

  • with iron-deficiency anaemia, or

  • aged ≥40 years with unexplained weight loss and abdominal pain, or

  • aged <50 years with rectal bleeding and either unexplained abdominal pain or unexplained weight loss, or

  • aged ≥50 years with unexplained rectal bleeding, abdominal pain, or weight loss, or

  • aged ≥60 years with anaemia in the absence of iron-deficiency.

The UK guidelines recommend FIT in people having previous negative FIT results. FIT should not be offered to people with a rectal mass, an unexplained anal mass, or unexplained anal ulceration before referral is considered.[111][138]

If the FIT result is ≥10 micrograms of haemoglobin/g of faeces, refer patients urgently (schedule an appointment within 2 weeks). If colorectal cancer is suspected, give safety-netting advice and do not delay referral, even if people do not return a faecal sample or have a FIT result of <10 micrograms of haemoglobin/g. Based on FIT results, investigations such as colonoscopy can be avoided in people who are less likely to have colorectal cancer, thus making the resources available to those who need them the most.[111][138]

Genetic tests

US and UK national guidelines recommend that all patients who are diagnosed with colon or rectal cancer should be tested for Lynch syndrome.[129][139][140]​​​​​ Test results may inform choice of systemic therapy, cancer risk reduction strategies in other sites, and testing of family members.

All patients with metastatic colorectal cancer should have tumour genotyped for RAS (KRAS and NRAS) and BRAF mutations individually or as part of a next-generation sequencing panel.[129][139] Testing should be performed only in certified laboratories.

Blood-based colorectal cancer screening

Blood-based tests (also known as liquid biopsy) have been developed in recent times to aid colorectal cancer screening.[141][142]​​ Studies comparing blood-based tests with established diagnostic tests such as FIT found that blood-based tests were less sensitive and expensive.[143][144]​​​ Blood-based testing may be performed over no screening but should not replace the existing tests. The Septin 9 blood test is the only FDA-approved test for serum colorectal cancer screening in adults who refuse testing with other tests endorsed by the US Preventive Services Task Force.[145]​ None of the guidelines endorse this test for routine colorectal cancer screening.[145]

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