Colorectal cancer

Introduction

Colorectal cancer (CRC) refers to malignant tumours arising from the colon or rectum, typically from adenomatous polyps. The vast majority (~95%) are adenocarcinomas. It is the third most common cancer in the UK and a major cause of cancer-related mortality.

Peak Incidence

• Most commonly diagnosed in individuals aged 60–79 years.
• Risk increases with age, family history, inflammatory bowel disease (especially ulcerative colitis), and certain hereditary syndromes (e.g. Lynch syndrome, familial adenomatous polyposis).

Pathophysiology

• CRC develops via the adenoma–carcinoma sequence, which involves the stepwise accumulation of genetic mutations (e.g. APC, KRAS, p53) in colonic epithelial cells.
• Chronic inflammation (e.g. in IBD) can also drive dysplasia.
• Tumours may present anywhere in the large bowel, with symptoms depending on their location:
  • Right-sided tumours tend to present with anaemia and weight loss.
  • Left-sided tumours more often cause change in bowel habit or obstruction.

Symptoms

• Change in bowel habit
  • Looser stools, increased frequency, or constipation
  • Tenesmus (incomplete evacuation) if rectal involvement
• Rectal bleeding (without obvious benign cause such as haemorrhoids)
• Unexplained weight loss
• Unexplained abdominal pain, particularly if persistent
• Fatigue (secondary to iron-deficiency anaemia)

Signs

• Iron-deficiency anaemia
  • Microcytic anaemia
  • Low ferritin
• Palpable abdominal or rectal mass
• Signs of bowel obstruction, especially in left-sided lesions:
  • Colicky abdominal pain
  • Abdominal distension
  • Vomiting
  • Absolute constipation

Diagnosis

Primary Care Assessment

• Use the Faecal Immunochemical Test (FIT) in patients with red-flag symptoms (see below).
• Refer for urgent colonoscopy (2WW) if FIT is positive (≥10 µg Hb/g faeces) or high clinical suspicion exists.

NICE Referral Criteria (Suspected CRC – FIT testing offered if applicable):

• Adults with:
  • A palpable abdominal mass
  • A persistent change in bowel habit
  • Iron-deficiency anaemia
  • Aged ≥40 with unexplained weight loss and abdominal pain
  • Aged <50 with rectal bleeding and either weight loss or abdominal pain
  • Aged ≥50 with rectal bleeding
  • Aged ≥60 with anaemia, even in the absence of iron deficiency

Investigations

• FIT – detects human haemoglobin in stool.
• Colonoscopy – gold standard; allows biopsy and polypectomy.
• Flexible sigmoidoscopy – useful for rectal bleeding; limited to distal colon.
• CT colonography – alternative if colonoscopy is contraindicated or incomplete.
• Staging:
  • CT thorax, abdomen, pelvis (CT TAP) – assesses for metastases.
  • Pelvic MRI / endorectal ultrasound – used in rectal cancer for local staging.
• Bloods:
  • FBC (look for microcytic anaemia)
  • Iron studies
  • Carcinoembryonic antigen (CEA) – baseline for monitoring treatment response

Complications

• Bowel obstruction
• Bowel perforation
• Fistula formation
• Peritoneal carcinomatosis – with ascites
• Intra-abdominal abscess
• Surgical complications – anastomotic leak, stoma-related issues
• Chemotherapy side effects – neutropenia, mucositis, diarrhoea, neuropathy
• Radiotherapy effects – strictures, chronic diarrhoea

Management

Surgical Management (Stage I–III)

• Surgical resection is first-line:
  • Right hemicolectomy – caecal and ascending colon tumours
  • Left hemicolectomy – distal transverse and descending colon
  • Sigmoid colectomy – sigmoid colon
  • Total proctocolectomy – considered in high-risk hereditary syndromes (e.g. FAP, Lynch syndrome)

Rectal Cancer

• Anterior resection – if sphincter-preserving
• Abdomino-perineal resection (APR) – if low rectal tumour involves sphincter complex

Adjuvant / Neoadjuvant Therapy

• Adjuvant chemotherapy (e.g. FOLFOX) in stage II–III
• Neoadjuvant chemoradiotherapy for locally advanced rectal cancer to improve resection rates and reduce recurrence

Stage IV / Metastatic Disease

• Neoadjuvant chemotherapy followed by staged colectomy and resection of metastases (e.g. liver or lung)
• Palliative chemotherapy (e.g. FOLFOX or FOLFIRI)
• Stenting for obstructing rectal/sigmoid tumours
• Monoclonal antibodies (e.g. cetuximab for KRAS wild-type, anti-VEGF therapies)

Follow-up

• After curative treatment:
  • CT TAP and CEA levels every 3 months for 2 years, then every 6 months for the next 3 years
  • Colonoscopy at 1 year post-resection, then at 3 years and 5 years