Colorectal Cancer (CRC)
Summary
Colorectal Cancer (CRC) is a malignancy arising from the colonic or rectal epithelium, most commonly adenocarcinoma arising from pre-existing adenomatous polyps (Adenoma-Carcinoma Sequence). It is the 3rd most common cancer worldwide and the 2nd leading cause of cancer death. Risk factors include age, family history, hereditary syndromes (FAP, Lynch Syndrome), IBD, and dietary factors (Red meat, Low fibre). Presentation depends on location: Right-sided tumours (Caecum/Ascending) often present with iron deficiency anaemia and weight loss, while Left-sided tumours (Sigmoid/Rectum) present with rectal bleeding, change in bowel habit, and obstruction. Diagnosis is by colonoscopy and biopsy, with CT for staging. Treatment involves surgical resection (Hemicolectomy, Anterior Resection, APR), adjuvant chemotherapy (Dukes C/Stage III), and neoadjuvant chemoradiotherapy for rectal cancer.
Key Facts
- Epidemiology: 3rd most common cancer. 2nd leading cause of cancer death. Peak age >60.
- Pathogenesis: Adenoma-Carcinoma Sequence (APC -> KRAS -> TP53 mutations).
- Right-Sided Presentation: Silent. Iron deficiency anaemia. Weight loss. RIF mass.
- Left-Sided Presentation: PR bleeding. Change in bowel habit. Obstruction.
- Screening (UK): FIT (Faecal Immunochemical Test) every 2 years (Ages 50-74).
- Staging: TNM / Dukes (A, B, C, D).
- Treatment: Surgery +/- Adjuvant Chemotherapy +/- Neoadjuvant Chemoradiotherapy (Rectal).
Clinical Pearls
"Right Side = Anaemia, Left Side = PR Bleeding + Obstruction": Right-sided tumours are "silent" – they bleed slowly causing iron deficiency anaemia. Left-sided tumours cause symptoms earlier due to smaller lumen.
"Iron Deficiency in a Man or Post-Menopausal Woman = Exclude CRC": Unexplained IDA mandates GI investigation (Upper + Lower).
"Adenoma-Carcinoma Sequence": CRC develops over ~10 years from normal mucosa -> Adenoma (APC mutation) -> Carcinoma (KRAS, TP53).
"2-Week Wait": In the UK, patients with red flag symptoms (Rectal bleeding + Change in bowel habit >40yo) are referred urgently via 2WW pathway.
Why This Matters Clinically
CRC is common and curable if detected early. Screening programmes (FIT, Colonoscopy surveillance) significantly reduce mortality. Recognising red flag symptoms and urgent referral saves lives.
Incidence
- 3rd Most Common Cancer Worldwide.
- Incidence UK: ~42,000 new cases/year.
- Age: Peak >60 years. Rising in younger adults.
- Sex: Slight male predominance.
Risk Factors
| Factor | Notes |
|---|---|
| Age | Risk increases with age. |
| Family History | First-degree relative with CRC doubles risk. |
| FAP (Familial Adenomatous Polyposis) | APC mutation. 100s of polyps. ~100% CRC risk by 40. |
| Lynch Syndrome (HNPCC) | Mismatch Repair genes (MLH1, MSH2). ~80% lifetime CRC risk. |
| Inflammatory Bowel Disease (IBD) | Ulcerative Colitis > Crohn's. Risk increases with duration. |
| Diet | Red/Processed meat. Low fibre. |
| Obesity | |
| Smoking / Alcohol | |
| Previous Adenomas | Surveillance required. |
Adenoma-Carcinoma Sequence (Vogelstein Model)
| Step | Mutation | Feature |
|---|---|---|
| Normal Mucosa | ||
| Hyperplasia | ||
| Early Adenoma | APC (Tumour Suppressor Loss) | Adenomatous polyp formation. |
| Intermediate Adenoma | KRAS (Oncogene Activation) | Growth. |
| Late Adenoma / Carcinoma | TP53 (Tumour Suppressor Loss) | Malignant transformation. |
| Invasive Carcinoma | Invasion through bowel wall. | |
| Metastasis | Lymph nodes, Liver, Lungs. |
This sequence takes ~10 years – The basis for screening with colonoscopy/polyp removal.
Microsatellite Instability (MSI)
- Alternative pathway (~15% of CRCs).
- Defective DNA Mismatch Repair (MMR).
- Associated with Lynch Syndrome.
- Often Right-sided. Better prognosis. May not respond to 5-FU.
Right-Sided Tumours (Caecum, Ascending Colon)
| Feature | Notes |
|---|---|
| Iron Deficiency Anaemia | Occult blood loss. Fatigue, Pallor. |
| Weight Loss | Malabsorption, Anorexia. |
| Abdominal Mass | RIF mass (May be palpable). |
| Vague Abdominal Pain | |
| Less Obstructive | Larger lumen. Liquid stool. |
Left-Sided Tumours (Sigmoid, Rectum)
| Feature | Notes |
|---|---|
| PR Bleeding (Rectal Bleeding) | Fresh blood mixed with stool. |
| Change in Bowel Habit | New onset constipation or looser stools. |
| Tenesmus | Sensation of incomplete evacuation (Rectal). |
| Obstruction | Narrower lumen. Solid stool. Presents late. |
| Mass on PR Exam | Low rectal tumours. |
Red Flags (2WW Referral Criteria – UK)
| Criteria | Age |
|---|---|
| Rectal Bleeding + Change in Bowel Habit | ≥40 |
| Iron Deficiency Anaemia | Any age (Men) / Post-Menopausal (Women) |
| Rectal Mass | Any age |
| Abdominal Mass | Any age |
| Unexplained Weight Loss + Abdominal Pain | ≥40 |
Colonoscopy (Gold Standard)
- Visualise entire colon.
- Biopsy for histology.
- Polypectomy for adenomas.
CT Colonography (Virtual Colonoscopy)
- If colonoscopy incomplete/contraindicated.
- Less sensitive for small polyps.
CT Thorax/Abdomen/Pelvis (Staging)
| Purpose | Notes |
|---|---|
| Staging | Local invasion, Lymph nodes, Liver/Lung metastases. |
| Pre-Op Planning | Resectability. |
MRI Pelvis (Rectal Cancer)
- Local staging of rectal tumours.
- T-stage, CRM (Circumferential Resection Margin).
CEA (Carcinoembryonic Antigen)
| Use | Notes |
|---|---|
| Not for Diagnosis | Low specificity. |
| Baseline Before Surgery | |
| Surveillance | Rising CEA may indicate recurrence. |
Bloods
| Test | Looking For |
|---|---|
| FBC | Anaemia (Microcytic IDA). |
| Iron Studies | Low Ferritin, Low Iron. |
| LFTs | Liver metastases. |
| CEA | Baseline. |
TNM Staging
| Stage | T | N | M | Survival |
|---|---|---|---|---|
| I | T1-T2 | N0 | M0 | >0% |
| IIA | T3 | N0 | M0 | ~80% |
| IIB | T4 | N0 | M0 | ~70% |
| IIIA-C | Any T | N1-N2 | M0 | 40-70% |
| IV | Any T | Any N | M1 | <10% |
Dukes Classification (Historical)
| Stage | Description | 5-Year Survival |
|---|---|---|
| A | Confined to Mucosa/Submucosa | >0% |
| B | Through Muscularis (No Nodes) | 70-85% |
| C | Lymph Node Involvement | 30-60% |
| D | Distant Metastases | <10% |
Principles
- MDT Discussion.
- Curative Surgery (If resectable).
- Adjuvant Chemotherapy (Dukes C / Node+).
- Neoadjuvant Chemoradiotherapy (Locally advanced Rectal).
- Palliative Care for metastatic disease.
Surgery by Location
| Location | Surgery |
|---|---|
| Caecum / Ascending Colon | Right Hemicolectomy. |
| Transverse Colon | Extended Right Hemicolectomy. |
| Descending / Sigmoid Colon | Left Hemicolectomy / Sigmoid Colectomy. |
| High Rectum | Anterior Resection (AR). +/- Temporary Loop Ileostomy. |
| Low Rectum | Low AR or Abdomino-Perineal Resection (APR). Permanent Colostomy with APR. |
Chemotherapy
| Indication | Regimen |
|---|---|
| Adjuvant (Dukes C / Stage III) | FOLFOX (5-FU/Oxaliplatin) or CAPOX (Capecitabine/Oxaliplatin). |
| Neoadjuvant (Rectal) | Chemoradiotherapy (5-FU + RT). Downstage tumour. |
| Metastatic | Palliative chemotherapy +/- Biologics (Bevacizumab, Cetuximab). |
Targeted Therapy
| Drug | Target | Notes |
|---|---|---|
| Bevacizumab | VEGF | Anti-angiogenic. |
| Cetuximab / Panitumumab | EGFR | Only for KRAS Wild-Type. |
Bowel Obstruction Emergency
| Scenario | Management |
|---|---|
| Left-Sided Obstructing CRC | Emergency Surgery (Hartmann's Procedure – Resection + End Colostomy). OR Self-Expanding Metal Stent (SEMS) as bridge to surgery. |
NHS Bowel Screening Programme
| Test | Age | Frequency |
|---|---|---|
| FIT (Faecal Immunochemical Test) | 50-74 years (England – Expanding to 50). | Every 2 years. |
| Positive FIT | Referral for Colonoscopy. |
Surveillance (High Risk)
| Risk | Colonoscopy Interval |
|---|---|
| Adenoma History (High Risk) | 3 yearly. |
| FAP | Annual from Puberty. Colectomy often indicated. |
| Lynch Syndrome | 1-2 yearly from age 25. |
| Ulcerative Colitis (Extensive) | Surveillance colonoscopy from 10 years after diagnosis. |
| Stage | 5-Year Survival |
|---|---|
| I | >0% |
| II | 70-85% |
| III | 30-60% |
| IV | <10% (May be higher with resectable liver mets) |
Key Guidelines
| Guideline | Organisation | Notes |
|---|---|---|
| NICE NG12 | NICE | Recognition and Referral of CRC. 2WW criteria. |
| NICE CG131 | NICE | Diagnosis and Management. |
| BSG Guidelines | British Society of Gastroenterology | Polyp surveillance. |
Scenario 1:
- Stem: A 65-year-old man presents with fatigue. Bloods show Hb 9g/dL with microcytic indices. Ferritin is low. What is the most important investigation?
- Answer: Upper and Lower GI Endoscopy (OGD + Colonoscopy). Iron deficiency anaemia in a man must exclude GI malignancy.
Scenario 2:
- Stem: A 55-year-old woman has new rectal bleeding mixed with stool and a change to looser stools for 6 weeks. How should she be referred?
- Answer: Urgent 2-Week Wait referral for suspected colorectal cancer.
Scenario 3:
- Stem: What is the Adenoma-Carcinoma Sequence?
- Answer: Stepwise mutation accumulation: APC (Adenoma) -> KRAS -> TP53 (Carcinoma). Takes ~10 years.
| Scenario | Urgency | Action |
|---|---|---|
| PR Bleeding + Change in Bowel Habit (≥40) | 2WW | Urgent colorectal referral. |
| Iron Deficiency Anaemia (Unexplained) | 2WW | Urgent GI referral (OGD + Colonoscopy). |
| Palpable Abdominal/Rectal Mass | 2WW | Urgent referral. |
| Positive FIT | Urgent | Colonoscopy referral. |
| Bowel Obstruction | Emergency | A&E / Surgical Admission. |
What is Bowel Cancer?
Bowel cancer is a cancer that starts in the large intestine (colon) or back passage (rectum). It usually develops slowly over many years from small growths called polyps.
What are the symptoms?
- Blood in your poo, or dark/black poo.
- A change in your normal bowel habit (e.g., going more often, looser stools).
- Unexplained tiredness or weight loss.
- Tummy pain or a lump.
How is it treated?
- Surgery: To remove the cancer.
- Chemotherapy: May be given before or after surgery.
- Radiotherapy: Sometimes used for cancers in the rectum.
Key Counselling Points
- Screening Saves Lives: "Take part in the NHS Bowel Screening programme (FIT test) when invited."
- Report Symptoms Early: "If you have blood in your poo or a change in bowel habit, see your GP."
- Polyp Removal Prevents Cancer: "Finding and removing polyps stops them turning into cancer."
| Standard | Target |
|---|---|
| 2WW referral for red flag symptoms | 100% |
| Colonoscopy within 28 days of referral | >0% |
| MDT discussion for all CRC diagnoses | 100% |
| Adjuvant chemotherapy offered for Stage III | 100% |
| CEA measured pre-operatively | >0% |
- Vogelstein (1990): Described the Adenoma-Carcinoma Sequence and the genetic mutations involved.
- National Bowel Screening (UK, 2006): Introduction of FOBt (now FIT) screening.
- Surgery: Miles' APR (1908) was the first curative operation for rectal cancer.
- NICE NG12. Suspected cancer: recognition and referral. 2015. nice.org.uk
- NICE CG131. Colorectal cancer: diagnosis and management. 2011. nice.org.uk
- Vogelstein B, et al. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988. PMID: 2843748
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. If you have symptoms of bowel cancer, please consult a healthcare professional.