Colorectal Cancer
Histology
~96% of cases are adenocarcinoma, typically originating in adenomatous polyps [Ref]
Risk Factors
~95% of colorectal cancers are sporadic [Ref1][Ref2]
- Non-modifiable risk factors: [Ref1][Ref2]
- Advanced age (esp. >50 y/o)
- Male sex
- Family history of colorectal cancer
- Polyps (colorectal adenomas)
- Medical conditions
- Inflammatory bowel disease (esp. ulcerative colitis – patients should be offered colonoscopy surveillance)
- Acromegaly
- Streptococcus gallolyticus infection (old name: Streptococcus bovis)
- Modifiable risk factors: [Ref1][Ref2]
- Obesity
- Type II diabetes
- Metabolic syndrome
- Physical inactivity
- Smoking and high alcohol consumption
- Western dietary pattern
- Red and processed meats
- Sugar-sweetened beverages
- High-fat food
The remaining 3-5% are related to hereditary colorectal cancer syndromes (see separate section below for more details):
- Lynch syndrome (hereditary non-polyposis colorectal cancer)
- Familial adenomatous polyposis (FAP)
- Peutz-Jeghers syndrome (PJS)
Clinical Features
Colorectal cancer can be asymptomatic, especially in early stages.
Constitutional Symptoms
Non-specific constitutional symptoms:
- Weight loss
- Anorexia
- Fever
- Night sweats
- Fatigue
Change in bowel habits / rectal bleeding / iron deficiency anaemia are relatively more specific to colorectal cancer (see local bowel effects below for more details)
Local Bowel Effects
Prevalence of colorectal cancer by anatomical site: sigmoid colon > ascending colon > rectum > caecum > transverse colon > descending colon > rectosigmoid junction [Ref]
Clinical presentation based on anatomical site: [Ref1][Ref2]
| Category | Anatomical site | Typical presentation |
|---|---|---|
| Right-sided colon cancer (proximal) | Caecum, ascending colon, hepatic flexure, transverse colon | Patients typically present at a more advanced stage (late presentation), due to non-specific symptoms:
|
| Left-sided colon cancer (distal) | Splenic flexure, descending colon, sigmoid colon | Patients typically present earlier:
Acute large bowel obstruction is also a common presentation (this is more likely on the left side as it has a smaller lumen and contains solid faeces) |
| Rectal cancer | Rectum | Patients typically present early on:
|
When classified into three anatomical regions, proximal colon cancer is the most common, followed by rectal cancer, and then distal colon cancer. [Ref]
Metastatic Features
The most common site of metastasis is the liver (via the hepatic portal vein), typically presenting as: [Ref]
- Ascites
- Hepatomegaly
- RUQ pain
- Jaundice
- Anorexia
Peritoneal carcinomatosis is a terminal feature of abdominal cancers
- Definition: metastatic spread of cancer cells diffusely over the peritoneal lining, leading to multiple tumour implants
- Presents with abdominal pain, distension, ascites, bowel obstruction
- Very poor prognosis
Lower rectal cancers are more likely to metastasise to the lungs, as the lower rectum is drained by the inferior rectal vein (part of the systemic venous system that drains directly into the vena cava without bypassing the liver). [Ref]
Screening
The NHS bowel cancer screening programme is in place:
- Target population: 50-74 y/o
- Frequency: every 2 years
- Method: home FITFaecal immunochemical testing test
- If FITFaecal immunochemical testing test is abnormal → refer for colonoscopy
- If normal → return to normal screening (2 yearly)
Investigation and Diagnosis
Digital Rectal Examination (DRE)
DRE is a simple bedside examination that should be performed in ALL patients with suspected colorectal cancer, particularly rectal lesions
- Useful to screen for palpable rectal tumours and for assessing tumour location and sphincter involvement
- Blood on the glove after a DRE may indicate a proximal tumour location
Primary Care – Suspected Lower GI Cancer Pathway
Note that since 2021, NICE recommends using FIT to risk-stratify patients before urgent referral, replacing the prior practice of direct referral for colonoscopy based solely on clinical suspicion or red-flag symptoms.
Red flags for lower GI cancer:
- Abdominal mass
- Change in bowel habit
- Iron deficiency anaemia
- <50 y/o AND rectal bleeding AND unexplained weight loss OR abdominal pain
- >40 y/o AND unexplained weight loss AND abdominal pain
- >50 y/o AND unexplained rectal bleeding OR abdominal pain OR weight loss
- >60 y/o AND anaemia (even in the absence of iron deficiency)
If any of the above red flags are present:
- First, offer a quantitative FITFaecal immunochemical testing test
- If FITFaecal immunochemical testing test is +ve (>10 mcg of Hb per g of faeces), then refer via the suspected cancer pathway (for colonoscopy)
Exceptions to the FIT pathway:
- If there is a rectal mass / unexplained anal mass / unexplained anal ulceration → consider suspected cancer pathway referral (without performing a FIT test first)
Secondary Care
Gold standard: colonoscopy with biopsy
Alternative to colonoscopy (e.g. inability to tolerate bowel preparation / sedation, significant bleeding risk, anatomical challenges) [Ref]
- CT colonography (virtual colonoscopy) – but still requires bowel preparation
- Flexible sigmoidoscopy (mainly for anal / rectal / sigmoid cancer) – less invasive than colonoscopy and requires only enema preparation
- Capsule endoscopy (less commonly used)
Possible biochemical changes in colorectal cancer:
- Anaemia (most commonly iron deficiency anaemia)
- Elevated inflammatory markers (↑ CRP, platelets)
- Impaired LFTs and clotting profile indicate hepatic metastases
CEACarcinoembryonic antigen is the tumour marker of choice for colorectal cancer, however it should NOT be used for screening / diagnosis purposes. Its role is limited to assessing response to treatment and evaluating for recurrence
Staging
Perform CT TAPCT thorax, abdomen, pelvis to stage colorectal cancer
The Duke’s colorectal cancer staging is no longer up-to-date, however it corresponds well to the TNM system. It would be more reasonable to learn the Duke’s staging instead of the full TNM system:
| Duke stage | Description |
|---|---|
| A | Tumour confined to the bowel wall (mucosa / submucosa / muscularis propria) |
| B | Tumour extends through the bowel wall, but no lymph node involvement |
| C | Any regional lymph node involvement (regardless of depth of invasion) |
| D | Any distant metastasis |
Management
Disclaimer:
This article focuses primarily on surgical management and the types of colorectal resection based on tumour location. Details on systemic chemotherapy, biologic therapies, and complex oncologic pathways are minimally covered, as these topics are infrequently examined and often require individualised multidisciplinary decision-making.
Colon Cancer
Standard of care: surgical resection + adjuvant chemotherapy (for stage III and high-risk stage II patients)
- Open / laparoscopic resection is appropriate for colon cancer
- Adjuvant chemotherapy is NOT necessary for stage I and low-risk stage II disease
- Unlike in rectal cancer, neoadjuvant chemoradiotherapy is NOT routinely used for colon cancer
The standard surgical approach for resectable colon tumours involves:
- Colectomy (resection of tumour-bearing segment of colon), and
- Associated mesentery resection (including high ligation of primary feeding vessels), and
- Lymph node resection (draining intermediate and central nodes), and
- End-to-end anastomosis (to restore bowel continuity) when feasible (if not feasible → end stoma creation)
Typical types of resection, based on tumour location: [Ref1][Ref2][Ref3]
| Tumour location | Type of resection | Resected structures |
|---|---|---|
| Caecum or ascending colon | Right hemicolectomy |
|
| Near hepatic flexure or in the proximal transverse colon | Extended right hemicolectomy |
|
| Near splenic flexure or descending colon | Left hemicolectomy |
|
| Sigmoid colon | Sigmoid colectomy |
|
Hartmann’s procedure: [Ref]
- Hartmann’s procedure is an emergency surgery for acute obstructing or perforated left-sided colon tumour (esp. sigmoid colon tumours)
- Key steps:
- Sigmoid / rectosigmoid colectomy
- Formation of an end colostomy (with the proximal colon)
- Distal rectal sump closure
- A later elective reversal of the colostomy to restore bowel continuity is possible
Rectal Cancer
Standard of care: neoadjuvant chemoradiotherapy (to shrink the tumour), followed by surgical resection [Ref]
- Radiotherapy is a standard part of rectal cancer treatment because of its anatomical location which poses surgical challenges and its fixed retroperitoneal location also makes it more accessible for external beam radiotherapy
- Laparoscopic surgery is recommended for rectal cancer
Typical types of resection, based on tumour location: [Ref]
| Tumour location | Type of resection | Typical resection description |
|---|---|---|
| Upper rectal tumour (>5cm away from the anal verge) | Low anterior resection | Total mesorectal excision + anastomosis + temporary defunctioning loop ileostomy (to protect the distal colorectal anastomosis) |
| Lower rectal tumour (≤5 cm from he anal verge) | Abdominoperineal resection* | Resection of rectum, anal canal, and sphincter complex + permanent end colostomy |
*Abdominoperineal resection is automatically indicated if there is evidence of sphincter invasion by the tumour
Patient outcome in low anterior resection vs abdominoperineal resection:
- Low anterior resection carries a significant risk of low anterior resection syndrome, which presents as bowel dysfunction (urgency, frequency, clustering, faecal incontinence)
- The main problem with abdominoperineal resection is the need for a permanent stoma and significantly greater male sexual dysfunction
Disclaimer: this table provides a simplified summary for revision and exam purposes. In clinical practice, the choice between low anterior resection (including ultra-low anterior resection and intersphincteric resection) and abdominoperineal resection for low rectal tumours depends on several factors, including tumour proximity to the anal verge, sphincter involvement, patient comorbidities, and individual surgical assessment. Sphincter-preserving approaches may be feasible for some very low rectal tumours if adequate oncological margins and good postoperative function can be achieved.
Radiotherapy is a standard part of rectal cancer treatment to enhance local control and reduce recurrence risk, because the anatomical location (anatomical location of the rectum poses surgical challenges, but its fixed retroperitoneal location also makes it more accessible for external beam radiotherapy) and the risk of pelvic relapse is much higher compared to colon cancer.
Post-Colorectal Cancer Surveillance
Colonoscopic surveillance is necessary after curative resection:
- Perform a surveillance colonoscopy (“clearance colonoscopy”) 1 year after resection
- If the 1-year surveillance is clear → surveillance colonoscopy after 3 years (4 years after the resection)
Hereditary Cancer Syndrome
While there are many hereditary cancer syndromes associated with colorectal cancer, this section focuses on three key syndromes: Lynch syndrome and FAP, which are the two most prevalent, and PJS, which is less common but frequently featured in exams.
Lynch syndrome / HNPCC (Hereditary Non-Polyposis Colorectal Cancer)
Definition
Lynch syndrome is an autosomal dominant hereditary cancer syndrome caused by mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6)
Lynch syndrome is the most common hereditary cancer syndrome, accounting for ~3% of colorectal cancers. [Ref]
Clinical Manifestations
Patients are typically asymptomatic until the onset of cancer.
The key manifestation of Lynch syndrome is early-onset colorectal cancer (often <50 y/o)
- The lifetime risk of colorectal cancer is ~20-60% by 70 y/o (exact risk depends on the implicated gene – MLH1 and MSH2 mutation carriers have the highest risk)
- Right-sided colon tumour is predominant
Lynch syndrome also increases the risk of non-colorectal cancer (exact risk varies by source, but the order of prevalence of the top 3 remains fairly consistent): [Ref1][Ref2][Ref3]
- Endometrial cancer (up to ~65%)
- Gastric cancer (up to ~20%)
- Ovarian cancer (up to ~15%)
- Urothelial cancer (up to ~10%)
- Other (<5% risk)
- Small intestine cancer
- Skin cancer
- Brain tumour
- Biliary tract cancer
Investigation and Diagnosis
Clinical diagnostic criteria (Amsterdam II criteria) (3-2-1 rule): [Ref]
- 3: at least 3 relatives with Lynch syndrome-associated cancer, and
- 2: at least 2 consecutive generations affected, and
- 1: at least 1 relative diagnosed <50 y/o
Definitive testing: DNA testing for mutations in DNA mismatch repair genes [Ref]
Management
Key management aspects: [Ref]
| Management | Rationale |
|---|---|
| Surveillance colonoscopy every 1-2 years is mandatory (start at 20-25 y/o) | Allow early detection and removal of pre-cancerous lesions |
| Consider aspirin daily for >2 years | Aspirin is a proven chemopreventive agent in Lynch syndrome to lower colorectal cancer risk |
| Consider prophylactic hysterectomy and bilateral salpingo-oophorectomy after childbearing age (in women) | To reduce the risk of endometrial and ovarian cancer |
Routine prophylactic colectomy is NOT recommended upon diagnosis of Lynch syndrome; these patients should be managed with surveillance colonoscopy. Subtotal colectomy is only recommended if those with Lynch syndrome are diagnosed with colorectal cancer to reduce future cancer risk.
This should not be confused with the management of FAP, where prophylactic colectomy is routinely recommended upon diagnosis.
Familial Adenomatous Polyposis (FAP)
Definition
FAP is an autosomal dominant hereditary cancer syndrome caused by mutations in adenomatous polyposis coli (ACP) – a tumour suppressor gene.
Clinical Manifestation
The key manifestation of FAP is the development of MANY (hundreds to thousands) of adenomatous polyps in the colon and the rectum [Ref]
- The development of polyps begins in adolescence
- Without intervention, there is a 100% lifetime risk of progression into colorectal cancer (often by 40 y/o)
- Patients typically remain asymptomatic until colon cancer develops
Extra-colonic manifestations: [Ref]
- Duodenal and gastric polyps (classically fundic gland polyps) → ↑ risk of gastric cancer
- ↑ Risk of pancreatic cancer
- Osteomas (esp. of the skull and mandible)
- Dental abnormalities (e.g. supernumerary teeth, impacted teeth, odontomas, congenital absence of teeth)
- Congenital hyperplasia of the renal pigment epithelium
- Desmoid tumours (aggressive fibromatosis)
- Thyroid cancer
- Hepatoblastoma, adrenal adenoma, CNS tumours (notable medulloblastoma)
Gardner syndrome is a phenotypic variant within the FAP spectrum, characterised by particularly prominent extra-intestinal features like multiple osteomas and dental abnormalities, which may precede colonic findings.
Investigation and Diagnosis
Colonoscopy demonstrating>100 synchronous colorectal adenomas is diagnostic of classic FAP [Ref]
Assessment for other manifestations (apart from colonoscopy): [Ref1][Ref2]
- Upper GI endoscopy – to assess for gastric and duodenal polyps
- Ophthalmic examination (to screen for congenital hypertrophy of the retinal pigment epithelium)
- Thyroid ultrasound (to screen for papillary thyroid cancer)
- Abdominal CT / MRI (to screen for desmoid tumours)
Be aware that up to 25% of cases are de novo and may lack a family history.
Management
Corestone of management: early prophylactic colectomy (due to the 100% lifetime risk of progression into cancer) [Ref]
- Typically performed at late adolescence or early adulthood when the polyp burden becomes unmanageable or high-risk features are present (e.g. large size, dysplasia)
- 2 main types of surgery (the decision is highly individualised)
- Total proctocolectomy with ileal pouch-anal anastomosis (standard approach)
- Subtotal colectomy with ileorectal anastomosis (spares the rectum, only appropriate if there is a low burden of rectal polyps)
Another key aspect is surveillance: [Ref]
- Upper GI endoscopy
- Thyroid ultrasound
- Surveillance of rectal stump or ileal pouch (post-colectomy)
- Surveillance of other manifestations should be individualised
Peutz-Jeghers Syndrome (PJS)
Definition
PJS is an autosomal dominant hereditary cancer syndrome caused by mutations in STK11 (LKB1) – a tumour suppressor gene.
Clinical Manifestation
There are 3 key clinical manifestations of PJS: [Ref]
| Manifestation | Clinical features |
|---|---|
| Mucocutaneous lentigines | Dark-blue / brown macules found on the lips, oral mucosa, peri-oral skin, fingers and toes |
| Multiple hamartomatous polyps throughout the GI tract | Can present as intussusception (common childhood presentation) / bowel obstruction / GI bleeding / anaemia |
| Increased risk of malignancies | Key implicated cancers include:
|
-
PJS is characterised by hamartomatous polyps occurring throughout the entire GI tract, including the small bowel (especially jejunum), stomach, and colon.
-
In contrast, Lynch syndrome and FAP primarily involve polyps and tumour development predominantly in the colon and rectum, without significant involvement of the small intestine.
Management
Corestone of management: [Ref]
- Endoscopic surveillance (colonoscopy, upper GI endoscopy and small-bowel imaging like video capsule endoscopy, MR enterography)
- Polypectomy
- Screening for other cancers
References
NICE guideline Suspected cancer: recognition and referral
NICE guideline Colorectal cancer
NHS England Guidance Bowel cancer screening: programme overview