Colorectal cancer is the third most common cancer in the UK, with around 40,000 new cases each year, and the second highest mortality of any cancer.
Although like most cancers, the occurrence is strongly associated with age, it can occur in patients as young as 20yrs (with the incidence in patients in their 40s is rising), particularly in patients with inherited cancer syndromes.
In this article, we shall look at the risk factors, clinical features and management of colorectal cancer.
Colorectal cancers originate from the epithelial cells lining the colon or rectum, most commonly an adenocarcinoma. Rarer types include lymphoma (~1%), carcinoid (<1%), and sarcoma (<1%).
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.
Certain genetic mutations have been implicated in predisposing individuals to colorectal cancer, most notably:
Adenomatous polyposis coli (APC)
- A tumour suppressor gene, mutation of the APC gene results in growth of adenomatous tissue; associated with Familial Adenomatous Polyposis (FAP)
Hereditary nonpolyposis colorectal cancer (HNPCC)
- A DNA mismatch repair gene, mutation to HNPCC leads to defects in DNA repair; associated with Lynch syndrome
Approximately 75% of colorectal cancers are sporadic, developing in people with no specific risk factors.
However, potential risk factors include increasing age, family history, inflammatory bowel disease, low fibre diet, high processed meat intake, smoking, and high alcohol intake.
The common clinical features of bowel cancer include change in bowel habit, rectal bleeding, weight loss*, abdominal pain, and iron-deficiency anaemia.
Classically, clinical features vary slightly depending on the location of the cancer:
- Right-sided colon cancers – abdominal pain, occult bleeding / anaemia, mass in right iliac fossa, and often present late
- Left-sided colon cancers – rectal bleeding, change in bowel habit, tenesmus, mass in left iliac fossa or 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 change in bowel habit
- Positive occult blood screening test
*As opposed to upper GI malignancies, progressive weight loss is usually only present in colorectal cancer cases with associated metastasis (or rarely in sub-acute bowel obstruction)
The symptoms associated with colorectal cancer can have a variety of possible diagnoses, however the main differentials to consider:
- 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 on the pan or surface of the stool but rarely presents with abdominal discomfort or pain, altered bowel habits, or weight loss
Colorectal Cancer Screening
In the UK, screening is offered every 2 years to men and women aged 60-75 years. For most of the UK, a faecal immunochemistry test (FIT) is used, superseding the faecal occult test, which utilises antibodies against human haemoglobin to detect blood in faeces.
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%.
Routine bloods should be performed for all suspected cases. A full blood count (FBC) may show a microcytic anaemia (an iron-deficiency anaemia), as well as LFTs and clotting.
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.
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 colonography can be performed 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
- A full colonoscopy or CT colonogram is required to check for a 2nd (synchronous) tumour if not used initially
- MRI rectum (for rectal cancers only) to assess the depth of invasion and potential need for pre-operative chemotherapy
- Endo-anal ultrasound (for early rectal cancers, T1 or T2 only) to assess suitability for trans-anal resection
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 propria||90%|
|B||Extension through the muscularis propria||65%|
|C||Involvement of regional lymph nodes||30%|
All patients should be discussed with the multidisciplinary team (MDT). The only definitive curative option is surgery, although chemotherapy and radiotherapy have an important role as neoadjuvant and adjuvant* treatments, alongside their role in palliation.
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:
Right Hemicolectomy or Extended Right Hemicolectomy
- The surgical approach for caecal tumours or ascending colon tumours, with the extended option performed for any transverse 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.
- 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.
- 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.
- The surgical approach for high rectal tumours, typically if >5cm from the anus. This approach is favoured as leaves the rectal sphincter intact if an anastomosis is 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, which can then be reversed electively 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.
*Elective colectomies 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
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).
Chemotherapy is indicated typically in patients with advanced disease (adjuvant chemotherapy in Dukes’ C colorectal cancer has been found to reduce mortality by 25%).
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 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.
Very advanced 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 bowel obstruction in patients with left-sided tumours
- 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
*Stenting cannot be used in low rectal tumours due to the unpleasant side-effect of intractable tenesmus
- Key symptoms of colorectal cancer are change in bowel habit and rectal bleeding
- 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