Colorectal cancer
Colorectal cancer and polyps
Most colorectal cancers arise from adenomatous polyps through the adenoma-carcinoma sequence, and hereditary syndromes account for a minority with distinctive features. Right- and left-sided tumours present differently, Dukes or TNM stage predicts survival, and surgery, adjuvant therapy and screening follow clear rules.
Polyps
| Type | Malignant potential | Features |
|---|---|---|
| Hyperplastic | Minimal (small distal); serrated pathway when large/right-sided | Commonest polyp; rectosigmoid; saw-tooth crypts |
| Adenomatous | Premalignant | Tubular (commonest, lowest risk), tubulovillous, villous (highest risk; may cause mucus diarrhoea and hypokalaemia) |
| Sessile serrated lesion | Premalignant (BRAF, CpG methylation, microsatellite instability) | Right colon; flat |
| Hamartomatous | Low (syndromic risk) | Juvenile polyps (children, rectal bleeding, autoamputation), Peutz–Jeghers (pigmented lips/buccal mucosa, small bowel polyps leading to intussusception; STK11; increased cancers of GI, breast, pancreas, ovary) |
| Inflammatory (pseudopolyps) | None | Ulcerative colitis |
- Risk of malignancy in an adenoma rises with size (> 2 cm), villous histology, high-grade dysplasia, number.
- Polyps removed endoscopically (polypectomy, EMR); surveillance colonoscopy depends on number/size/histology.
Adenoma–carcinoma sequence (chromosomal instability pathway)
Normal mucosa, then APC loss (early; Wnt/β-catenin), then early adenoma, then KRAS mutation, then late adenoma, then p53 loss (and DCC/SMAD4, 18q), then carcinoma. About 85% of sporadic cancers.
- Microsatellite instability pathway (about 15%): mismatch repair defects (MLH1, MSH2, MSH6, PMS2) — Lynch syndrome or sporadic MLH1 hypermethylation; right-sided, mucinous, lymphocytic infiltrate, better stage prognosis; respond to immunotherapy.
Hereditary syndromes
| Syndrome | Gene | Features |
|---|---|---|
| Familial adenomatous polyposis (FAP) | APC (chromosome 5q), AD | Hundreds to thousands of adenomas from adolescence; colorectal cancer by about age 40 in nearly 100%, so prophylactic (procto)colectomy (late teens–20s); duodenal/periampullary adenomas (leading cause of death after colectomy), desmoid tumours, CHRPE (retinal pigmentation), fundic gland polyps |
| Gardner syndrome | APC variant | FAP + osteomas (jaw, skull), epidermoid cysts, desmoids, dental abnormalities |
| Turcot syndrome | APC or MMR | Polyposis + brain tumours (medulloblastoma/glioma) |
| Attenuated FAP, MUTYH-associated polyposis | APC; MUTYH (AR) | Fewer polyps, later onset |
| Lynch syndrome (HNPCC) | Mismatch repair genes, AD | Few polyps, right-sided cancers at young age (about 45), endometrial (commonest extracolonic), ovarian, gastric, small bowel, urothelial, pancreatic, brain cancers; Amsterdam criteria (3-2-1: three relatives, two generations, one under 50, FAP excluded); colonoscopy every 1–2 years from 25; aspirin reduces risk |
| Peutz–Jeghers, juvenile polyposis | STK11; SMAD4/BMPR1A | Hamartomas; cancer risk |
- Universal tumour testing for MMR deficiency identifies Lynch syndrome.
Risk factors for sporadic colorectal cancer
Age > 50, family history, diet (high red and processed meat, low fibre), obesity, smoking, alcohol, sedentary lifestyle, inflammatory bowel disease (UC — extent and duration (> 8–10 years), PSC; Crohn colitis), previous adenoma/cancer, ureterosigmoidostomy, acromegaly, *Streptococcus bovis* bacteraemia (association), radiation. Protective: fibre, exercise, aspirin, calcium.
Clinical presentation
| Right-sided (caecum, ascending) | Left-sided (descending, sigmoid) and rectum |
|---|---|
| Iron deficiency anaemia (occult bleeding), weight loss, fatigue, RIF mass, often late; obstruction rare (liquid contents, wide lumen) | Change in bowel habit, rectal bleeding (dark red, mixed with stool), tenesmus and incomplete evacuation (rectal), obstruction (narrower lumen, solid stool; "apple-core" lesion), mucus |
- Most cancers occur in the rectum and sigmoid (about 2/3).
- Complications: large bowel obstruction (commonest cause in adults), perforation, fistula (colovesical — pneumaturia), bleeding.
- Spread: direct, lymphatic, haematogenous to liver (portal vein — commonest site of distant metastases) and lung (low rectal tumours also via systemic veins), transcoelomic.
Investigations
- Colonoscopy with biopsy (investigation of choice; also detects synchronous tumours — about 3–5%); CT colonography if unfit.
- Staging: CT chest–abdomen–pelvis; MRI pelvis for rectal cancer (circumferential resection margin, nodes); endorectal ultrasound for early rectal tumours; PET for recurrence.
- CEA: not for diagnosis/screening; baseline and monitoring for recurrence after resection.
- FBC, LFTs.
Staging
| Dukes | Extent | Approximate 5-year survival |
|---|---|---|
| A | Confined to bowel wall (not beyond muscularis propria) | > 90% |
| B | Through bowel wall, nodes negative | About 70–80% |
| C | Lymph node metastases | About 40–60% |
| D (modified) | Distant metastases | < 10–15% |
- TNM is now standard (T1 submucosa, T2 muscularis propria, T3 through muscle into pericolic fat, T4 serosa/adjacent organs; N by number of nodes; M). At least 12 lymph nodes should be examined.
Treatment
- Colon cancer surgery (en bloc resection with mesentery, high vessel ligation — complete mesocolic excision):
| Site | Operation |
|---|---|
| Caecum, ascending colon, hepatic flexure | Right hemicolectomy (ileocolic, right colic, right branch of middle colic) |
| Transverse colon | Extended right hemicolectomy or transverse colectomy |
| Splenic flexure, descending | Left hemicolectomy |
| Sigmoid | Sigmoid colectomy (high anterior resection) |
| Upper/mid rectum | Anterior resection with total mesorectal excision (TME) ± defunctioning ileostomy |
| Low rectum involving sphincters/within about 2 cm | Abdominoperineal resection (permanent colostomy) |
| Emergency obstruction/perforation (left) | Hartmann procedure (resection, end colostomy, rectal stump) or resection with anastomosis ± stoma; colonic stent as bridge |
- Adjuvant chemotherapy (FOLFOX/CAPOX) for stage III (node-positive) and high-risk stage II colon cancer.
- Rectal cancer: neoadjuvant chemoradiotherapy or short-course radiotherapy for locally advanced/threatened margins, then TME; total neoadjuvant therapy; "watch and wait" after complete clinical response.
- Liver metastases: resection if limited (good long-term survival in selected patients); chemotherapy (anti-EGFR — cetuximab/panitumumab — only in RAS wild-type; bevacizumab).
- ERAS pathway; complications — anastomotic leak (days 5–7: fever, tachycardia, peritonitis; higher in low rectal anastomoses), ileus, wound infection, ureteric injury (left ureter in sigmoid/left resections), stoma problems, low anterior resection syndrome, sexual and urinary dysfunction (pelvic autonomic nerve damage).
Screening
- Faecal immunochemical test (FIT) (detects human haemoglobin — replaces guaiac FOBT), positive leads to colonoscopy.
- Colonoscopy every 10 years; flexible sigmoidoscopy; CT colonography.
- Screening reduces mortality (removing adenomas also reduces incidence).
- High-risk surveillance: FAP (annual sigmoidoscopy from 12–14), Lynch (colonoscopy every 1–2 years), IBD (from 8–10 years after onset), strong family history.
Anal cancer
Squamous cell carcinoma (HPV 16/18, HIV, anal intercourse, immunosuppression, smoking); below dentate line drains to inguinal nodes; treated primarily with chemoradiotherapy (Nigro), not surgery.
How FCPS asks it
Recalls test: polyp types and malignant risk (villous, size); adenoma–carcinoma genes (APC first); FAP gene, inheritance, extracolonic features and prophylactic surgery; Gardner and Turcot; Lynch syndrome genes, endometrial cancer, Amsterdam criteria; right versus left-sided presentation; commonest site; liver metastases; investigation of choice; CEA role; Dukes stages; operations by site (right hemicolectomy, APR versus anterior resection, TME, Hartmann); adjuvant chemotherapy for node-positive disease; neoadjuvant radiotherapy for rectal cancer; RAS testing before anti-EGFR therapy; anastomotic leak timing; FIT screening; anal cancer chemoradiotherapy.
Exam trap Right-sided colon cancer presents with iron deficiency anaemia; left-sided with change in bowel habit and obstruction.
Exam trap FAP (APC, autosomal dominant) leads to cancer in nearly all untreated patients — prophylactic colectomy.
Exam trap CEA is for monitoring recurrence, not for diagnosis or screening.
Test yourself on this topic
5 of the 37 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
After resection of a colon cancer, which single pathology finding most strongly predicts survival and the need for adjuvant chemotherapy?
Answer: Lymph node involvement
Stage is the main prognostic factor in colorectal cancer, and spread to regional lymph nodes (TNM N stage, formerly Dukes C) marks a large fall in survival. Node-positive disease is the main indication for adjuvant chemotherapy. At least 12 nodes should be examined to stage accurately. Tumour size matters much less than depth of invasion and nodal status.
Colorectal staging
- Node status (N stage)
- Node-positive: adjuvant chemo
- Examine ≥ 12 nodes
- Depth (T) matters more than size
Remember Nodes decide chemo.
Exam trap CEA is used to monitor for recurrence, not to diagnose.
Why the other options are wrong
- Tumour size in centimetres Less important than depth and nodes.
- Histological type Most are adenocarcinoma.
- Patient's age A patient factor, not tumour stage.
- CEA before surgery Useful for follow-up, less for staging.
An elderly woman passes large amounts of mucus per rectum and has weakness. Potassium is 2.8 mmol/L. Sigmoidoscopy shows a large soft frond-like rectal lesion. What is it?
Answer: Villous adenoma
Villous adenomas are often large and sessile, mostly in the rectum and sigmoid. They can secrete large amounts of potassium-rich mucus, causing hypokalaemia and dehydration. They have the highest risk of malignant change among adenomas (size over 2 cm, villous structure and high-grade dysplasia all raise risk). Treatment is complete excision.
Villous adenoma
- Large, sessile, rectum
- Mucus loss: hypokalaemia
- Highest malignant risk
- Risk rises with size >2 cm
Remember Fronds that leak potassium.
Exam trap Hyperplastic polyps are generally not premalignant.
Why the other options are wrong
- Hyperplastic polyp Small, low risk; no mucus loss.
- Tubular adenoma Usually small and pedunculated.
- Juvenile polyp Children; hamartomatous.
- Inflammatory pseudopolyp Linked to colitis.
A 66-year-old man has infective endocarditis of the aortic valve. Blood cultures grow Streptococcus gallolyticus (formerly S. bovis biotype I). Which of the following investigations is essential once he is stable?
Answer: Colonoscopy
Streptococcus gallolyticus is part of the bowel flora and is strongly associated with colorectal adenomas and carcinoma; bacteraemia with it may be the first sign of a tumour. It is thought to colonise and enter through abnormal colonic mucosa. Every patient with S. gallolyticus bacteraemia or endocarditis should have colonoscopy. Viridans streptococci, by contrast, point to a dental source.
S. gallolyticus
- Formerly S. bovis biotype I
- Linked to colorectal cancer
- Endocarditis or bacteraemia: colonoscopy
- Viridans streptococci: dental source
Remember S. gallolyticus in the blood: look in the colon.
Exam trap Do not stop at treating the endocarditis; a missed colon cancer can be found at an early stage.
Why the other options are wrong
- Dental panoramic X-ray For viridans streptococcal endocarditis from the mouth.
- Bone marrow biopsy Not indicated by this organism.
- Renal ultrasound Not related to this organism.
- Echocardiography of relatives Endocarditis is not inherited.
A 70-year-old woman has fatigue and Hb 8.2 g/dL with low ferritin. Her bowel habit is unchanged and she has no rectal bleeding. Which of the following is the most likely site of a colorectal cancer causing this picture?
Answer: Caecum or ascending colon
In the caecum and ascending colon the lumen is wide and the stool liquid, so a tumour rarely obstructs. Instead it bleeds slowly and invisibly, and the blood is mixed with stool, causing iron deficiency anaemia with few bowel symptoms. Left-sided and rectal tumours more often cause change in bowel habit, obstruction or visible bleeding. Unexplained iron deficiency in an older adult needs examination of both the colon and the upper gut.
Right colon cancer
- Wide lumen, liquid stool
- Rarely obstructs
- Occult bleeding: iron deficiency
- Few bowel symptoms
Remember Older adult with iron deficiency: scope the right colon.
Exam trap Iron deficiency in a man or a postmenopausal woman is GI cancer until proven otherwise.
Why the other options are wrong
- Sigmoid colon Narrow lumen with solid stool: obstruction and altered habit.
- Rectum and anal canal Bright red bleeding, tenesmus and change in habit.
- Splenic flexure region Often presents with obstruction.
- Rectosigmoid junction Narrow lumen: change in bowel habit and obstruction.
Two years after colectomy for familial adenomatous polyposis, a man has a firm, growing mass in the abdominal wall that has not spread. Histology shows bland fibroblasts infiltrating muscle. What is it?
Answer: Desmoid tumour
Desmoid tumours are locally aggressive, non-metastasising proliferations of fibroblasts that infiltrate surrounding tissue. They occur in FAP (especially Gardner syndrome, with osteomas and epidermoid cysts), often after surgery, in the abdominal wall or mesentery, and in women after pregnancy. They recur after excision; treatment includes observation, NSAIDs, hormonal therapy, surgery or radiotherapy.
Desmoid tumour
- Locally aggressive, no metastases
- FAP / Gardner, after surgery
- Abdominal wall, mesentery
- Bland fibroblasts infiltrate
- High recurrence
Remember FAP plus a growing scar mass: desmoid.
Exam trap Mesenteric desmoids are a major cause of death in FAP after colectomy.
Why the other options are wrong
- Subcutaneous lipoma Soft, encapsulated, fat cells.
- Metastatic adenocarcinoma Would show malignant glands.
- Incisional hernia No mass of fibroblasts.
- Rhabdomyosarcoma Malignant; children.
Where this sits in the CPSP syllabus
- Surgery & Allied, Paper 2: Oncology, Colorectal cancer and polyps
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