Colorectal Cancer
Colorectal cancer is the 4th most common cancer and 2nd leading cause of cancer death in the UK. Screening with FIT has improved early detection; 5-year survival is approximately 60%.
Key Facts
4th most common cancer in UK; ~42,000 new cases/year; 2nd leading cause of cancer death NHS Bowel Cancer Screening: FIT (faecal immunochemical test) every 2 years, ages 56-74 (expanding to 50-74) Adenoma-carcinoma sequence: ~95% of colorectal cancers arise from adenomatous polyps via APC → KRAS → TP53 mutations Left-sided (descending/sigmoid): Change in bowel habit, rectal bleeding, obstruction Right-sided (caecum/ascending): Iron-deficiency anaemia, weight loss, mass (often late presentation) Dukes' classification: A (confined to wall ~95% 5-year), B (through wall ~80%), C (lymph nodes ~60%), D (distant metastases ~10%) CEA: Tumour marker — useful for monitoring recurrence (not screening) 2-week wait referral (NICE NG12): ≥40 with unexplained weight loss + abdominal pain; ≥50 with unexplained rectal bleeding; ≥60 with IDA or change in bowel habit; any age with rectal/abdominal mass
Overview
Key Facts
Colorectal cancer is a major public health challenge. The national bowel cancer screening programme has significantly improved early detection and outcomes.
Epidemiology
~42,000 new cases annually in UK. Lifetime risk ~5-6%. Peak age 60-80 years. Slight male predominance (M:F ~1.2:1). Incidence increasing in younger adults (<50).
Aetiology
- Adenoma-carcinoma sequence (~95% of cases): Normal mucosa → adenomatous polyp → dysplasia → carcinoma over 10-15 years
- Key mutations: APC (gatekeeper) → KRAS → SMAD4 → TP53
- Inflammatory pathway: UC/Crohn's colitis → dysplasia → cancer
- Microsatellite instability pathway: DNA mismatch repair deficiency (Lynch syndrome)
Risk factors:
- Age >50, family history (first-degree relative = 2-3× risk), IBD (UC > Crohn's)
- Lynch syndrome (HNPCC): Autosomal dominant; ~3-5% of CRC; MLH1, MSH2, MSH6, PMS2 mutations
- FAP: APC gene; >100 polyps; near 100% CRC risk by age 40 without prophylactic colectomy
- Modifiable: Red/processed meat, obesity, physical inactivity, alcohol, smoking
Pathophysiology
- Adenocarcinoma (~95%) arising from colonic epithelium
- Spread: Direct invasion → lymphatic (regional nodes) → haematogenous (liver most common, then lung) → transcoelomic (peritoneal)
Clinical Presentation
Left-Sided (Sigmoid, Descending)
- Change in bowel habit (increased frequency, looser stools)
- Rectal bleeding (bright red or dark, mixed with stool)
- Tenesmus (sensation of incomplete evacuation)
- Obstructive symptoms (narrow calibre stool, colicky pain)
- May present as emergency with LBO or perforation
Right-Sided (Caecum, Ascending)
- Iron-deficiency anaemia (occult blood loss) — often the presenting feature
- Weight loss, fatigue
- Palpable RIF mass
- Less likely to obstruct (wider lumen, liquid stool)
Red Flags/2WW Referral Criteria (NICE NG12)
- ≥40 with unexplained weight loss + abdominal pain
- ≥50 with unexplained rectal bleeding
- ≥60 with IDA or change in bowel habit
- Rectal or abdominal mass at any age
- FIT ≥10 μg Hb/g faeces in symptomatic patients
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Diverticular disease | LIF pain, altered bowel habit, bleeding | CT, colonoscopy |
| IBD | Younger patient, diarrhoea, extra-intestinal features | Colonoscopy, faecal calprotectin |
| IBS | Younger, no red flags, normal investigations | Diagnosis of exclusion |
| Haemorrhoids | Bright red rectal bleeding on wiping, no weight loss | Proctoscopy |
| Polyps (adenomatous) | Usually asymptomatic, found on screening | Colonoscopy |
Diagnosis / Investigation
Bedside
- FIT (faecal immunochemical test): Quantitative; ≥10 μg Hb/g faeces in symptomatic patients → colonoscopy
- PR examination: Assess for rectal mass
Bloods
- FBC: Iron-deficiency anaemia (low MCV, low ferritin)
- LFTs: Liver metastases (raised ALP, GGT)
- CEA: Baseline pre-operative (for monitoring recurrence post-treatment)
- U&Es: Baseline
Imaging/Endoscopy
- Colonoscopy: Gold standard — allows visualisation, biopsy, polypectomy
- CT colonography: Alternative if colonoscopy incomplete or contraindicated
- CT chest/abdomen/pelvis: Staging (lung and liver metastases)
- MRI pelvis: Staging for rectal cancer (see separate topic)
- PET-CT: If surgical resection of metastases considered
Management
Surgical (Curative Intent)
Colon cancer:
- Right hemicolectomy: Caecal/ascending colon tumours
- Extended right hemicolectomy: Hepatic flexure/transverse
- Left hemicolectomy: Descending colon
- Sigmoid colectomy: Sigmoid tumours
- Emergency: Hartmann's procedure if obstruction/perforation (resection + end colostomy)
Laparoscopic approach is standard where possible — faster recovery, fewer complications (CLASICC trial)
Adjuvant Chemotherapy
- Dukes' C (node-positive): 6 months adjuvant chemotherapy — FOLFOX (5-FU + oxaliplatin) or capecitabine + oxaliplatin
- Dukes' B: Consider if high-risk features (T4, perforation, <12 nodes sampled, poorly differentiated, lymphovascular invasion)
Metastatic Disease
- Liver metastases: Consider hepatic resection if suitable (5-year survival ~30-40% after resection)
- Lung metastases: Consider pulmonary metastasectomy if isolated
- Palliative chemotherapy: FOLFOX or FOLFIRI ± biological agents (cetuximab if KRAS wild-type; bevacizumab)
- Immunotherapy: Pembrolizumab for MSI-high/dMMR metastatic CRC
Referral Criteria
- 2WW referral as per NICE NG12 criteria
- MDT discussion for all confirmed cases
- Specialist HPB surgery for liver metastasis resection
Prognosis
- Overall 5-year survival: ~60%
- Stage-specific (Dukes'): A ~95%, B ~80%, C ~60%, D ~10%
- Screening-detected cancers: Earlier stage, better survival
- Adjuvant chemotherapy (Dukes' C): Improves 5-year survival by ~10-15%
- Liver metastasis resection: 5-year survival ~30-40% (vs ~5% without)
- Recurrence: ~30% within 5 years; most in first 2 years; CEA monitoring aids early detection
- Follow-up: CT at 1 and 3 years, colonoscopy at 1 year then 3-yearly (NICE NG151)
Other Relevant Information
Dukes' Classification vs TNM
| Dukes' | TNM | Description | 5-Year Survival |
|---|---|---|---|
| A | T1-2 N0 M0 | Confined to bowel wall | ~95% |
| B | T3-4 N0 M0 | Through bowel wall, no nodes | ~80% |
| C | Any T, N1-2, M0 | Lymph node involvement | ~60% |
| D | Any T, Any N, M1 | Distant metastases | ~10% |
Hereditary CRC Syndromes
| Syndrome | Gene | Risk | Key Features |
|---|---|---|---|
| Lynch (HNPCC) | MLH1, MSH2, MSH6, PMS2 | ~80% lifetime | Proximal, MSI-high, young onset |
| FAP | APC | ~100% by 40 | >100 polyps, prophylactic colectomy |
| Peutz-Jeghers | STK11 | ~39% lifetime | Hamartomatous polyps, mucocutaneous pigmentation |