Colorectal Cancer

Colorectal cancer is the third most common cancer in the UK, with around 40,000 new cases each year, and the second highest mortality figures of any cancer.

The occurrence is strongly associated with age, as over 85% of presentations are in those >60yrs, although it can occur in patients in their 20-30yrs, particularly in patients with inherited cancer syndromes.

In this article, we shall look at the risk factors, clinical features and management of colorectal cancer.


Aetiology

Colorectal cancers originate from the epithelial cells lining the colon or rectum, typically as adenocarcinomas. Rarer rectal cancers include lymphoma (1.3%), carcinoid (0.4%), and sarcoma (0.3%).

Most colorectal cancers develop via a progression of normal mucosa to colonic adenoma (colorectal ‘polyps’) to invasive adenocarcinoma (termed the “adenoma-carcinoma sequence”). Adenomas may be present for 10 years or more before becoming malignant and progression to adenocarcinoma occurs in approximately 10% of adenomas.

Some genetic mutations have been implicated in predisposing individuals to colorectal cancer, most notably:

  • Adenomatous polyposis coli (APC) gene
    • Early APC gene (a tumour suppressor gene) mutation and inactivation results in growth of adenomatous tissue. Also responsible for the development of Familial Adenomatous Polyposis (FAP).
  • Hereditary nonpolyposis colorectal cancer (HNPCC)
    • Mutation to DNA mismatch repair (MMR) genes leading to defects in DNA repair, commonly accounting for the familial risk associated with colorectal cancer.
Fig 1 - The adenoma-carcinoma sequence.

Fig 1 – The adenoma-carcinoma sequence.


Risk Factors

Approximately 75% of colorectal cancers are sporadic, developing in people with no specific risk factors.

In the remaining 25%, potential risk factors include age (>60yrs), family history, inflammatory bowel disease, low fibre diet, high processed meat intake, smoking, and high alcohol intake.


Clinical Features

The common clinical features of bowel cancer include change in bowel habit, rectal bleeding, weight loss*, abdominal pain, and iron-deficiency anaemia.

Classically, symptoms vary slightly depending on the location of the cancer:

  • Right-sided colon cancers – abdominal pain, occult bleeding, or mass in right iliac fossa.
  • Left-sided colon cancers – rectal bleeding, change in bowel habit or tenesmus, or mass in left iliac fossa / mass on PR exam.

In the UK, NICE guidance recommends that patients should be referred for urgent investigation of suspected bowel cancer if:

  •  ≥40yrs with unexplained weight loss and abdominal pain
  • ≥50yrs with unexplained rectal bleeding
  • ≥60yrs with iron‑deficiency anaemia or changes in bowel habit
  • Positive occult faecal blood test

*As opposed to upper GI malignancies, progressive weight loss is only present in colorectal cancer cases with associated metastasis (or rarely in sub-acute bowel obstruction)


Differential Diagnosis

The symptoms associated with colorectal cancer can have a variety of possible diagnoses, including:

  • Inflammatory bowel disease: The average age of onset of inflammatory bowel disease is younger (20-40yrs) than with colorectal cancer and typically presents with diarrhoea containing blood and mucus.
  • Haemorrhoids: Bright red rectal bleeding covering the surface of the stool and rarely presents with abdominal discomfort or pain, altered bowel habits, or weight loss.
  • Diverticulitis: Can present with blood in stool and change in bowel habit, yet likely to cause systemic features of inflammation.

Colorectal Cancer Screening

In the UK, screening is offered every 2 years to men and women aged 60-75 years. It is conducted using faecal occult blood (FOB) home testing kits, whereby 3 separate stool samples are required for analysis.

If any of the samples are positive, patients are offered an appointment with a specialist nurse and further investigation via colonoscopy.

Since its introduction in 2006, the NHS Bowel Cancer Screening Programme has increased detection of colorectal cancer in people aged 60-69 by 11%.


Investigations

Laboratory tests

Routine bloods should be performed for all suspected cases. A full blood count (FBC) may show a microcytic anaemia (particularly if the cancer is on the right side of the colon), as well as U&Es, LFTs, and coagulation screens.

The tumour marker Carcinoembryonic Antigen (CEA) should not be used as a diagnostic test, due to poor sensitivity and specificity, however it is used to monitor disease progression and should be conducted both pre- and post-treatment, screening for recurrence.

Imaging

The gold standard for diagnosis of colorectal cancer is via colonoscopy with biopsy. If a colonoscopy is not suitable for the patient, such as from frailty, co-morbidities, or intolerance, a flexible sigmoidoscopy or CT colography can be performed (although not as sensitive or specific as colonoscopy) for initial diagnosis

Once the diagnosis is made, several other investigations are required (primarily for staging):

  • CT scan (Chest/Abdomen/Pelvis) to look for distant metastases and local invasion
    • Full colonoscopy or CT colonogram to check for a 2nd (synchronous) tumour, if not used initially
  • MRI rectum (rectal cancers only) to assess the depth of invasion (and hence need for pre-operative chemotherapy).
  • Endo-anal ultrasound (early rectal cancers (T1 or T2) only) to assess suitability for trans-anal resection.
Fig 1 - Endoscopic image of colorectal adenocarcinoma. GI cancers can cause peforation via obstruction, or via direct invasion of the bowel wall.

Figure 2 – Endoscopic image of colorectal adenocarcinoma.

Dukes’ Staging

Like many other tumours, colorectal cancers are staged according to the TNM system. This stages the cancer according to the depth the tumour invades the bowel wall (T stage), the extent of spread to local lymph nodes (N stage), and whether or not there are distant metastasis (M stage). The Duke’s staging system has now been largely superseded but is still used at some centres for additional staging detail

Stage Description 5 Year Survival (%)
A Confined beneath the muscularis mucosa 90
B Extension through the muscularis mucosa 65
C Involvement of regional lymph nodes 30
D Distant metastasis <10

Management

All patients should be discussed with the multidisciplinary team (MDT). The only definitive curative treatment is surgery, yet chemotherapy and radiotherapy have an important role as neoadjuvant/adjuvant* treatment, as well as in palliation.

Surgical

Surgery is the mainstay of curative management for localised malignancy in the bowel. The general plan in most surgical management plans is suitable regional colectomy, to ensure the removal of the primary tumour with adequate margins and lymphatic drainage, followed either by primary anastomosis or formation of a stoma to restore bowel function.

  • Right Hemicolectomy and Extended Right Hemicolectomy
    • The surgical approach for caecal or ascending colon tumours. During the procedure the ileocolic, right colic, and right branch of the middle colic vessels (branches of the SMA) are divided and removed with their mesenteries. An extended right hemicolectomy is typically performed for any transverse colon cancers.
  • Left Hemicolectomy
    • The surgical approach for descending colon tumours. Similar to the right hemicolectomy, the left branch of the middle colic vessels (branch of SMA/SMV), the inferior mesenteric vein, and the left colic vessels (branches of the IMA/IMV) are divided and removed with their mesenteries.
  • Sigmoidcolectomy
    • The surgical approach for sigmoid colon tumours. In this instance, the IMA is fully dissected out with the tumour in order to ensure adequate margins are obtained.
  • Anterior Resection
    • The surgical approach for high rectal tumours, typically if >5cm from the anus. This approach is favoured in rectal carcinoma as resection leaves the rectal sphincter intact and functioning if anastamosis performed, unlike AP resections. 
    • Often a defunctioning loop ileostomy is performed to protect the anastomosis and reduce complications in the event of an anastomotic leak. This is then reversed electively approximately four to six months later.
  • Abdominoperineal (AP) Resection
    • The surgical approach for low rectal tumours, typically <5cm from the anus. This technique involves excision of the distal colon, rectum and anal sphincters, resulting in a permanent colostomy.

*Bowel resections are often performed laparoscopically as this offers faster recovery times, reduced surgical site infection risk, and reduced post-operative pain, with no difference in disease recurrence or overall survival rates when compared to open surgery.

Hartmann’s Procedure

This procedure is used in emergency bowel surgery, such as bowel obstruction or perforation. This involves a complete resection of the recto-sigmoid colon with the formation of an end-colostomy and the closure of the rectal stump.

Fig 3 - AP resection, an approach used for low rectal tumours.

Fig 3 – AP resection, an approach used for low rectal tumours.

Chemotherapy

Chemotherapy is indicated typically in patients with metastatic disease (adjuvant chemotherapy in Dukes’ C colorectal cancer has been found to reduce mortality by 25%). The decision of which chemotherapy agents to use will be decided by the MDT discussions.

An example chemotherapy regime for patients with metastatic colorectal cancer is FOLFOX, comprised of Folinic acid, Fluorouracil (5-FU), and Oxaliplatin, which has been demonstrated to significantly improvement in 3-year disease-free survival for patients with advanced colon cancer.

Radiotherapy

Radiotherapy can be used in rectal cancer (it is rarely given in colon cancer due to the risk of damage to the small bowel), most often as neo-adjuvant treatment.

It is of particular use in patients with rectal cancers which look on MRI to have a “threatened” circumferential resection (i.e. within 1mm). They can undergo pre-operative long-course chemo-radiotherapy to shrink the tumour, thereby increasing the chance of complete resection and cure.

Palliative Care

Many high staging colorectal cancers will be managed palliatively, focusing on reducing cancer growth and ensuring adequate symptom control. Whilst a large variety of palliative care options are available to such patients, important surgical options that can offered include:

  • Endoluminal stenting can be used to relieve acute large bowel obstruction in patients with left-sided tumours, yet they cannot be used in low rectal tumours due to the unpleasant side-effect of intractable tenesmus. The main side-effects of stents are perforation, migration, and incontinence
  • Stoma formation can be performed for patients with acute obstruction, usually with either a defunctioning stoma or palliative bypass.
  • Resection of secondaries, not commonly performed but can done with adjuvant chemotherapy for any liver metastases

 

Key Points

  • Age, family history, and diet are important risk factors for developing colorectal cancer
  • Gold-standard diagnosis is made via colonoscopy with biopsy; CEA is only useful in monitoring treatment efficacy and disease recurrence, not to aid diagnosis
  • Surgical resection remains the only definitive cure
  • Colorectal cancer screening in the UK is offered every 2 years to men and women aged 60-75 years, and is conducted using faecal occult blood

Quiz

Question 1 / 4
All of the following are risk factors for colorectal cancer except?

Quiz

Question 2 / 4
All of the following are used to diagnose metastasis in colon cancer except?

Quiz

Question 3 / 4
Which of the following tumour depth identifications is correct?

Quiz

Question 4 / 4
Which of the following statements is false?

Results

Further Reading

Colorectal adenocarcinoma: risks, prevention and diagnosis
British Medical Journal

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