Rectal cancer is a malignant tumour arising from the rectal mucosa, usually within the distal 15 cm of the large intestine measured from the anal verge. It is one of the most common gastrointestinal malignancies and is frequently grouped with colon cancer under the term colorectal cancer (CRC). However, rectal cancer differs from colon cancer in its anatomy, patterns of spread, and treatment approach, particularly regarding the role of radiotherapy.

Approximately 95% of rectal cancers are adenocarcinomas, arising from glandular epithelial cells of the rectal mucosa. Other less common histological types include mucinous adenocarcinoma, signet-ring cell carcinoma, neuroendocrine tumours, lymphoma, and squamous cell carcinoma.

Management depends on tumour stage, location within the rectum, histological characteristics, and patient fitness. Treatment commonly involves a combination of surgery, chemotherapy, and radiotherapy, with curative intent in localized disease and palliative treatment in metastatic disease.

Epidemiology

Rectal cancer is a major cause of cancer-related morbidity and mortality worldwide.

Epidemiological characteristics include:

• Incidence increases with age.

• More common after 50 years of age.

• Slightly more common in males.

• Incidence is increasing in younger adults in some populations.

• Adenocarcinoma accounts for approximately 95% of cases.

The burden of colorectal cancer is increasing in many low- and middle-income countries due to lifestyle changes, dietary factors, obesity, and population ageing.

Risk factors

Several environmental, genetic, and medical factors increase the risk of rectal cancer.

1. Inherited genetic syndromes

Examples include:

• Familial adenomatous polyposis (FAP).

• Lynch syndrome (Hereditary Non-Polyposis Colorectal Cancer).

• MUTYH-associated polyposis.

2. Dietary factors

Increased risk is associated with:

• High consumption of red meat.

• High consumption of processed meat.

• Low dietary fibre intake.

• Low intake of fruits and vegetables.

3. Smoking

Long-term tobacco use increases colorectal cancer risk.

4. Alcohol abuse

Heavy alcohol consumption contributes to colorectal carcinogenesis.

5. Inflammatory bowel disease

Particularly:

• Ulcerative colitis.

• Crohn’s colitis.

Risk increases with disease duration and extent.

6. Type 2 diabetes mellitus

Associated with increased colorectal cancer risk through metabolic and inflammatory mechanisms.

7. Obesity

Obesity contributes through:

• Insulin resistance.

• Chronic inflammation.

• Altered growth factor signalling.

8. Personal or family history

• Previous colorectal polyps.

• Previous colorectal cancer.

• First-degree relative with colorectal cancer.

Pathophysiology

Most rectal cancers develop through the adenoma-carcinoma sequence, in which benign adenomatous polyps gradually undergo malignant transformation.

The progression typically involves:

1. Normal rectal mucosa.

2. Adenomatous polyp formation.

3. Low-grade dysplasia.

4. High-grade dysplasia.

5. Invasive adenocarcinoma.

Genetic alterations commonly involve:

• APC gene mutations.

• KRAS mutations.

• TP53 mutations.

• Microsatellite instability pathways.

Tumour spread occurs through:

• Direct local invasion.

• Lymphatic dissemination.

• Hematogenous metastasis.

Common metastatic sites include:

• Liver.

• Lung.

• Peritoneum.

• Bone.

Because of the confined pelvic anatomy, rectal cancers frequently invade adjacent pelvic structures if untreated.

Clinical presentation

Clinical manifestations depend on tumour size, location, stage, and degree of bowel obstruction.

Early disease may be asymptomatic or present with subtle bowel habit changes.

Advanced disease commonly presents with bleeding, altered bowel habits, and symptoms of obstruction.

Symptoms

Change in bowel habits

Patients may report:

• Constipation.

• Diarrhoea.

• Alternating constipation and diarrhoea.

• Narrow or ribbon-like stools.

Sense of incomplete bowel emptying

Also known as tenesmus.

Patients may complain of:

• Persistent urge to defecate.

• Incomplete evacuation after bowel movements.

Rectal bleeding

May present as:

• Bright red blood per rectum.

• Blood mixed with stool.

• Occult bleeding.

Abdominal symptoms

• Abdominal discomfort.

• Abdominal distension.

• Features of intestinal obstruction.

Constitutional symptoms

• Unexplained weight loss.

• Fatigue.

• Loss of appetite.

Symptoms of advanced disease

• Bone pain.

• Respiratory symptoms.

• Jaundice from liver metastases.

• Progressive weakness.

Clinical signs

General findings

• Pallor due to chronic blood loss.

• Cachexia.

• Weight loss.

Abdominal findings

• Abdominal mass.

• Abdominal distension.

• Signs of bowel obstruction.

Digital rectal examination findings

Digital rectal examination (DRE) may reveal:

• Rectal mass.

• Irregular lesion.

• Ulcerative growth.

• Circumferential narrowing.

• Fixed tumour.

Signs of metastatic disease

• Hepatomegaly.

• Ascites.

• Supraclavicular lymphadenopathy.

• Respiratory signs due to lung metastases.

Differential diagnosis

Differential diagnoses include:

• Colonic adenomatous polyps.

• Hemorrhoids.

• Anal fissure.

• Inflammatory bowel disease.

• Diverticular disease.

• Infectious colitis.

• Irritable bowel syndrome.

• Rectal prolapse.

• Colorectal lymphoma.

Diagnostic criteria

Rectal cancer should be suspected in patients presenting with:

• Persistent rectal bleeding.

• Change in bowel habits.

• Tenesmus.

• Unexplained weight loss.

• Iron deficiency anaemia.

• Rectal mass on examination.

Definitive diagnosis requires:

• Endoscopic visualization of the lesion.

• Histological confirmation from biopsy.

Investigations

Laboratory investigations

Full blood count (FBC)

Used to assess:

• Anaemia.

• Baseline treatment status.

Renal function tests (RFTs)

Includes:

• Urea.

• Creatinine.

Required before contrast imaging and chemotherapy.

Liver function tests (LFTs)

Assess:

• Hepatic metastases.

• Baseline organ function.

Carcinoembryonic antigen (CEA)

Useful for:

• Baseline assessment.

• Monitoring treatment response.

• Surveillance after treatment.

Stool for occult blood

Detects occult gastrointestinal bleeding.

Imaging investigations

Chest X-ray (CXR)

Used to evaluate:

• Pulmonary metastases.

Double-contrast barium enema

May demonstrate:

• Filling defects.

• Mucosal irregularities.

• Obstructive lesions.

Abdominal and pelvic ultrasound

Useful for:

• Assessment of liver metastases.

• Initial abdominal evaluation.

CT scan of abdomen and pelvis

Used for:

• Local staging.

• Detection of nodal disease.

• Identification of distant metastases.

Endoscopic investigations

Sigmoidoscopy

Allows:

• Direct visualization of rectal lesions.

• Biopsy collection.

Colonoscopy

Preferred because it:

• Evaluates the entire colon.

• Detects synchronous lesions.

• Allows biopsy confirmation.

Clinical examination

Digital rectal examination (DRE)

An essential component of diagnosis.

Allows assessment of:

• Tumour location.

• Tumour mobility.

• Distance from anal verge.

• Sphincter involvement.

Histopathology

Biopsy confirms:

• Adenocarcinoma.

• Histological subtype.

• Tumour differentiation.

Staging

Rectal cancer is staged using the TNM staging system.

T – Primary tumour

Determined by:

• Depth of bowel wall invasion.

• Involvement of adjacent organs.

N – Regional lymph nodes

Determined by:

• Number of involved lymph nodes.

M – Distant metastases

Assessment of spread to:

• Liver.

• Lung.

• Peritoneum.

• Bone.

Staging determines whether treatment is curative or palliative.

Management

Management should follow a multidisciplinary approach involving:

• Colorectal surgeons.

• Medical oncologists.

• Radiation oncologists.

• Gastroenterologists.

• Pathologists.

Treatment depends on:

• Stage.

• Tumour location.

• Performance status.

• Presence of metastases.

Management pathway:

1. Confirm diagnosis.

2. Stage disease.

3. Assess operability.

4. Administer neoadjuvant therapy where indicated.

5. Perform definitive surgery.

6. Administer adjuvant treatment if required.

7. Conduct long-term surveillance.

Non-pharmacological treatment

Surgical treatment

Surgery is the primary curative treatment.

Procedures may include:

Low anterior resection (LAR)

Used for:

• Upper and middle rectal cancers.

• Preservation of anal sphincter function.

Abdominoperineal resection (APR)

Used when:

• Tumour involves the anal sphincter.

• Sphincter preservation is not feasible.

Results in permanent colostomy.

Management of obstruction

Options include:

• Diverting colostomy.

• Resection of obstructing tumour.

• Palliative surgical procedures.

Radiotherapy

Radiotherapy plays an important role in rectal cancer.

Neoadjuvant radiotherapy

Given before surgery to:

• Reduce tumour size.

• Improve resectability.

• Reduce local recurrence.

Adjuvant radiotherapy

Given after surgery in selected patients.

Palliative radiotherapy

Used for:

• Pain control.

• Bleeding control.

• Symptomatic pelvic disease.

Pharmacological treatment

Neoadjuvant chemoradiotherapy

Concurrent chemoradiotherapy

5-Fluorouracil (5-FU) – 350 mg/m² – intravenous infusion over 30 minutes – day 1 to day 5ANDLeucovorin – 20 mg/m² – intravenous infusion over 30 minutes – day 1 to day 5

Administered:

• During week 1 and week 5 of radiotherapy.

Concurrent radiotherapy:

• 45 Gy in 25 fractions over 5 weeks.

Surgery is performed:

• 4–10 weeks after completion of chemoradiotherapy.

Postoperative chemotherapy following neoadjuvant treatment

Commence:

• 3–10 weeks after surgery.

5-Fluorouracil (5-FU) – 50 mg/m² – intravenous infusion over 30 minutes – day 1 to day 5PLUSLeucovorin – 20 mg/m² – intravenous infusion over 30 minutes – day 1 to day 5

Frequency:

• Every 21 days.

Duration:

• 4 cycles.

Adjuvant chemoradiotherapy

Concurrent phase

5-Fluorouracil (5-FU) – 500 mg/m² – intravenous infusion over 30 minutes – day 1 to day 5 and day 29 to day 33

Concurrent radiotherapy:

• 45 Gy in 25 fractions over 5 weeks.

Consolidation chemotherapy

Four weeks after completion of chemoradiotherapy:

5-Fluorouracil (5-FU) – 450 mg/m² – intravenous bolus – day 1 to day 5

Frequency:

• Every 4 weeks.

Duration:

• 2 cycles.

Alternative concurrent regimen

Capecitabine – 825 mg/m² – oral – every 12 hours during radiotherapy

Management of metastatic disease

Regimen 1 (Modified FOLFOX)

Oxaliplatin – 85 mg/m² – intravenous infusion over 2 hours – day 1ANDLeucovorin – 400 mg/m² – intravenous infusion over 20 minutes – day 1AND5-Fluorouracil – 400 mg/m² – intravenous bolus – day 1followed by5-Fluorouracil – 1200 mg/m²/day – continuous intravenous infusion – days 1–2

Frequency:

• Every 14 days.

Duration:

• 6–12 cycles.

May be given with:

Bevacizumab – 5 mg/kg – intravenous infusion over 1 hour – day 1

OR

Cetuximab – 500 mg/m² – intravenous infusion over 2 hours – day 1

Regimen 2 (CAPEOX/XELOX)

Oxaliplatin – 130 mg/m² – intravenous infusion over 2 hours – day 1ANDCapecitabine – 1000 mg/m² – oral – every 12 hours – day 1 to day 14

Frequency:

• Every 21 days.

Duration:

• 4–8 cycles.

May be combined with:

Bevacizumab – 5 mg/kg – intravenous infusion over 1 hour – day 1

Regimen 3

Capecitabine – 1000 mg/m² – oral – every 12 hours – day 1 to day 14

Frequency:

• Every 21 days.

Duration:

• 6 cycles.

Management according to underlying cause

Localized rectal cancer

Management:

• Surgical resection.

• Neoadjuvant chemoradiotherapy for locally advanced disease.

• Adjuvant therapy where indicated.

Locally advanced rectal cancer

Management:

• Neoadjuvant chemoradiotherapy.

• Definitive surgery.

• Adjuvant chemotherapy.

Metastatic rectal cancer

Management:

• Systemic chemotherapy.

• Targeted therapy where indicated.

• Palliative radiotherapy.

• Symptom-directed supportive care.

Referral

All patients with suspected or confirmed rectal cancer should be referred to specialized oncology and colorectal surgery centres.

Urgent referral indications

• Large rectal mass.

• Intestinal obstruction.

• Significant rectal bleeding.

• Severe anaemia.

• Evidence of metastatic disease.

• Rapidly progressive symptoms.

Complications

Disease-related complications

• Intestinal obstruction.

• Perforation.

• Gastrointestinal bleeding.

• Severe anaemia.

• Liver metastases.

• Lung metastases.

• Peritoneal carcinomatosis.

Treatment-related complications

Surgery

• Anastomotic leak.

• Surgical site infection.

• Stoma-related complications.

Chemotherapy

• Neutropenia.

• Diarrhoea.

• Peripheral neuropathy (oxaliplatin).

• Mucositis.

Radiotherapy

• Radiation proctitis.

• Radiation cystitis.

• Pelvic fibrosis.

Prognosis

Prognosis depends on:

• TNM stage.

• Nodal involvement.

• Presence of distant metastases.

• Completeness of surgical resection.

• Response to chemoradiotherapy.

Early-stage disease treated with curative intent has favourable outcomes, whereas metastatic disease is associated with significantly reduced survival.

Prevention

Preventive measures include:

• Maintaining a healthy body weight.

• Increasing dietary fibre intake.

• Reducing consumption of red and processed meat.

• Smoking cessation.

• Limiting alcohol consumption.

• Regular physical activity.

• Appropriate management of inflammatory bowel disease.

• Screening and surveillance of high-risk individuals and hereditary cancer syndromes.

• Early evaluation of rectal bleeding and persistent bowel habit changes.