Colorectal cancer

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Colorectal adenocarcinoma develops through conventional adenomatous and serrated precursor routes, with a minority driven by inherited or colitis-associated mechanisms. Symptoms reflect site and stage. A right-colon tumour may grow large before narrowing the lumen and present through anaemia; a sigmoid lesion may obstruct; a rectal tumour may cause urgency and incomplete evacuation. Population screening detects occult blood before symptoms and prevents cancer by removing precursors.

Symptomatic FIT is a triage tool, not an absolute rule-out test. A positive result accelerates investigation, while persistent concerning symptoms still require safety-netting and sometimes referral after a low result. Colonoscopy obtains tissue, marks the lesion when needed and clears the remaining colon. CT colonography visualises the whole colon when endoscopy fails but cannot biopsy. Pathology confirms adenocarcinoma and tests MMR or MSI from diagnosis.

Staging separates colon and rectum. CT identifies liver, lung, peritoneal and nodal disease. Rectal MRI defines tumour height, depth beyond muscularis, mesorectal fascia, extramural venous invasion and sphincter or sidewall relationships. Those features determine whether surgery proceeds first or follows neoadjuvant treatment. Complete mesocolic or mesorectal plane surgery and adequate nodal assessment are critical pathological quality measures.

Treatment remains potentially curative beyond stage III. Selected T1 lesions are removed endoscopically; stage II and III disease is resected with risk-adapted chemotherapy; locally advanced rectal disease uses radiation and systemic therapy to secure margins and reduce distant relapse. Limited liver, lung or peritoneal disease may undergo resection, ablation or carefully selected cytoreduction. In unresectable disease, molecular testing enables immune, EGFR, BRAF or HER2-directed treatment within precise indications.

Key points

Right-sided cancer commonly produces iron-deficiency anaemia, fatigue and vague pain; left-sided disease more often causes altered habit and obstruction, and rectal cancer causes bleeding, urgency and tenesmus.
Use quantitative FIT to triage appropriate symptomatic patients, but a low result does not overrule a rectal or abdominal mass, persistent unexplained symptoms, iron deficiency or strong clinical concern.
The diagnostic reference standard is complete colonoscopy with biopsy, careful lesion localisation and assessment for synchronous neoplasia; CT colonography is the principal alternative when colonoscopy is incomplete or unsuitable.
Obtain contrast CT chest, abdomen and pelvis for distant staging. For rectal cancer, high-resolution MRI pelvis is the reference local staging test and should report mesorectal fascia, nodes, extramural vascular invasion and sphincter anatomy.
Measure baseline CEA for prognosis and later surveillance, but do not use a normal CEA to exclude cancer or a raised value without imaging to diagnose recurrence.
Test every newly diagnosed colorectal cancer for mismatch-repair deficiency or microsatellite instability to screen for Lynch syndrome and inform prognosis and advanced immune treatment.
Selected en-bloc endoscopically removed T1 cancer with favourable depth, differentiation, lymphovascular, budding and margin features may be cured without segmental surgery after expert pathology review.
Colon cancer treatment is oncological segmental resection with intact mesocolic planes and adequate nodes, followed by adjuvant chemotherapy for stage III and selected high-risk stage II disease.
Rectal treatment is MRI risk adapted: early disease may undergo local or total mesorectal excision, while threatened margins or higher-risk disease may need neoadjuvant radiotherapy, chemoradiation or total neoadjuvant therapy.
A complete clinical response after rectal neoadjuvant therapy can enter watch-and-wait only within a specialist programme with intensive examination, endoscopy and MRI; it is not no follow-up.
Metastatic liver or lung disease may still be curable through resection or ablation after hepatobiliary or thoracic MDT review; do not call all stage IV disease permanently unresectable.
Advanced systemic therapy uses RAS, BRAF, MMR or MSI and selected HER2 and other markers, tumour side, performance and prior treatment to choose targeted and immune options.
Stoma siting and counselling, fertility and sexual function, prehabilitation, nutrition and enhanced recovery begin before treatment and continue into surveillance.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Sporadic adenoma and serrated pathways

Most cancers arise through accumulated APC–WNT, KRAS, TP53 or serrated BRAF and epigenetic changes in a precursor polyp over years.

Inherited susceptibility

Lynch mismatch-repair variants, APC-associated polyposis, MUTYH-associated polyposis and rarer hamartomatous syndromes cause earlier, multiple and family-clustered colorectal neoplasia.

Chronic colonic inflammation

Longstanding extensive ulcerative colitis or Crohn colitis creates inflammation-associated dysplasia risk related to duration, activity, extent, primary sclerosing cholangitis and family history.

Age and modifiable exposure

Older age, processed and red meat, alcohol, smoking, obesity, diabetes and inactivity increase risk, while fibre, activity and screening polypectomy reduce population burden.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Precursor clones gain invasive ability
Stepwise genomic and epigenetic alterations convert benign glandular epithelium into dysplasia that breaches muscularis mucosae and gains lymphovascular access.
2
Anatomy shapes presentation
Right-sided tumours bleed occultly into a capacious lumen, whereas left-sided circumferential lesions narrow solid stool and rectal lesions cause bleeding and tenesmus.
3
Mesenteric and pelvic planes govern spread
Colon cancer follows mesocolic nodes and vessels, while rectal cancer threatens the mesorectal fascia, sphincters, pelvic sidewall and extramural veins.
4
Portal drainage favours liver metastasis
Tumour cells entering mesenteric veins seed liver first, while rectal systemic venous drainage and later dissemination also produce lung, peritoneal, bone and brain disease.
5
Mismatch repair creates immune visibility
Deficient mismatch repair produces microsatellite instability and a high neoantigen burden, identifying Lynch risk and predicting benefit from immune checkpoint blockade in advanced disease.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Right-sided cancer

Iron-deficiency anaemia, fatigue, weight loss, vague right abdominal pain or a mass may occur without visible bleeding or early obstruction.

Left-sided cancer

Progressive constipation or looser stool, colicky pain, distension and visible blood reflect a narrower lumen and more solid contents.

Rectal cancer

Bleeding, tenesmus, urgency, reduced stool calibre and incomplete evacuation require digital rectal examination and complete colonic assessment.

Inherited pattern

Young diagnosis, multiple colorectal cancers, endometrial or other Lynch tumours or numerous polyps requires genetics-led testing and family surveillance.

Acute obstruction or perforationRed flag

Absolute constipation, marked distension, faeculent vomiting, peritonism, sepsis or free air requires urgent CT and colorectal surgical care.

Metastatic presentation

Hepatomegaly, jaundice, ascites, dyspnoea, pleural fluid, bone pain or supraclavicular nodes can reveal disseminated disease.

Red flags requiring action

Peritonism, fever, shock, free air or rapidly worsening abdominal pain suggests perforated cancer and needs emergency surgery and antibiotics.
Absolute constipation, distension, colicky pain, vomiting or an incompetent ileocaecal valve with caecal dilatation suggests threatened large-bowel obstruction.
Persistent rectal bleeding, iron-deficiency anaemia, unexplained weight loss or altered bowel habit requires a colorectal pathway even when haemorrhoids are present.
A palpable rectal or abdominal mass, supraclavicular node, hepatomegaly, ascites or obstructive jaundice suggests advanced disease.
New back pain, leg weakness, perineal sensory change or bladder dysfunction with pelvic recurrence raises neural or spinal compression.
Fever or severe diarrhoea during chemotherapy may indicate neutropenic sepsis, enterocolitis or immune colitis and requires urgent acute-oncology assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line quantitative FIT in eligible symptomatic careFirst stepFirst line
Why
Measure faecal haemoglobin to prioritise colorectal investigation in adults with compatible lower-GI symptoms.
Interpretation and limitations
Use the current threshold and referral pathway; a value below threshold needs safety-netting and does not overrule a mass, persistent iron deficiency or unresolved clinical concern.
02
Reference complete colonoscopy with biopsy
Why
Confirm histology, localise the primary, assess obstruction and detect synchronous cancer and polyps.
Interpretation and limitations
Document relation to anatomical landmarks, tattoo when helpful for surgery and use CT colonography or postoperative completion when the scope cannot traverse safely.
03
First-line contrast CT chest abdomen and pelvisFirst line
Why
Stage liver, lung, peritoneal, nodal and locally invasive disease and identify potentially resectable metastases.
Interpretation and limitations
Characterise indeterminate liver lesions with liver MRI and discuss oligometastatic disease in the organ-specific MDT before declaring it incurable.
04
Reference high-resolution rectal MRI
Why
Define rectal T category, mesorectal fascia, extramural vascular invasion, nodes, sphincter, peritoneal reflection and pelvic sidewall.
Interpretation and limitations
Use a dedicated rectal protocol and MDT review; the threatened circumferential margin and EMVI often matter more to neoadjuvant planning than T category alone.
05
Baseline CEA
Why
Provide prognostic and postoperative surveillance context when the tumour secretes this marker.
Interpretation and limitations
Smoking, inflammation and other cancers can raise CEA and some colorectal cancers never do; use serial change with imaging, never as standalone diagnosis.
06
Universal MMR or MSI testing
Why
Screen for Lynch syndrome, refine stage-II prognosis and identify advanced cancers likely to benefit from checkpoint inhibition.
Interpretation and limitations
Loss patterns guide BRAF or MLH1 methylation and germline referral; tumour deficiency is not automatically inherited and requires the reflex pathway.
07
Advanced molecular panel
Why
Select EGFR, BRAF, HER2, immune and rare fusion-directed treatment in unresectable metastatic disease.
Interpretation and limitations
Use validated tissue or plasma testing for a specific treatment decision and consider tumour side, prior therapy and current NICE criteria.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Haemorrhoids or anal disease

Bright bleeding and discomfort may arise distally, but visible haemorrhoids do not explain iron deficiency, weight loss, altered habit or a positive FIT automatically.

Inflammatory bowel disease

Bloody diarrhoea, urgency and abdominal pain can reflect active colitis; endoscopy and histology must also assess inflammation-associated dysplasia and cancer.

Diverticular and vascular disease

Diverticulitis can form a stricture and diverticulosis or angiodysplasia can bleed, sometimes coexisting with a proximal or occult tumour.

Functional bowel disorder

Irritable bowel syndrome causes recurrent pain and altered stool without bleeding, anaemia, mass or progressive obstruction, but new later-life change warrants reassessment.

Other abdominal or pelvic malignancy

Ovarian, endometrial, prostate, bladder, small-bowel and metastatic cancers can invade bowel or create masses and require lineage-specific pathology.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01SymptomaticUse FIT with clinical safety-nettingFirst stepAn adult has rectal bleeding, altered bowel habit, iron deficiency, weight loss or compatible abdominal symptoms.

1Assess haemodynamic state, obstruction, abdominal and rectal masses and full-blood-count evidence of iron deficiency, activating emergency care when unstable.
2Request quantitative FIT where appropriate and refer at the current threshold, but refer or investigate persistent red flags and masses regardless of a low result.
3Complete colonoscopy and biopsy or CT colonography with a route to tissue, then communicate diagnosis and obtain site-specific staging through the colorectal MDT.

02Colon cancerResect in the mesocolic plane and risk-adapt chemotherapyA non-metastatic colon primary is technically resectable and the patient is fit for curative treatment.

1Optimise anaemia, nutrition, frailty and comorbidity, mark a potential stoma and plan segmental vascular and lymphatic resection from complete colonic imaging.
2Perform oncological colectomy with intact mesocolic planes and adequate nodal harvest, using laparoscopy or open surgery according to anatomy and emergency status.
3Review pT, nodes, margins, vascular or perineural invasion, obstruction or perforation and MMR at the MDT and offer adjuvant chemotherapy for stage III and selected high-risk stage II disease.

03Rectal cancerLet MRI risk define the sequenceBiopsy confirms rectal adenocarcinoma and high-resolution pelvic MRI is available.

1Classify height, sphincter, T and N, circumferential margin and EMVI and discuss fertility, bowel, urinary, sexual and stoma outcomes before treatment.
2Use surgery first for suitable lower-risk disease and short-course radiation, chemoradiation or total neoadjuvant therapy when margins, nodes or systemic relapse risk justify pretreatment.
3Perform local excision or total mesorectal excision as indicated and offer watch-and-wait after a complete response only in an expert intensive-surveillance programme.

04MetastaticTest resectability before accepting palliationCT identifies liver, lung, peritoneal or other distant colorectal metastasis.

1Obtain liver MRI, PET-CT or biopsy when it will clarify extent or lineage and discuss liver, lung and peritoneal disease in the appropriate specialist MDT.
2Use surgery, ablation, radiation or conversion systemic therapy when complete local treatment is plausible, sequencing the primary and metastases around symptoms and biology.
3For unresectable disease, use MMR or MSI, RAS, BRAF and selected HER2 findings, tumour side and fitness to choose systemic therapy and define response and stopping criteria.

05ObstructionResuscitate and choose durable decompressionCancer causes acute or impending large-bowel obstruction without uncontrolled perforation.

1Resuscitate, correct electrolytes, give antibiotics when ischaemia or perforation is possible and obtain urgent contrast CT to define level, caecal threat and metastases.
2Choose emergency resection, defunctioning stoma or selected self-expanding metal stent as bridge or palliation through experienced colorectal and endoscopy teams.
3DefinitiveObtain complete colonic evaluation after decompression when safe and return the patient to staging, pathology, nutrition and definitive MDT planning.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Reduces recurrence after resection of stage III and selected high-risk stage II colorectal cancer and is also used in some advanced protocols.

CAPOX adjuvant chemotherapy

A common 21-day cycle gives oxaliplatin 130 mg/m² intravenously on day 1 plus capecitabine 1,000 mg/m² orally twice daily on days 1 to 14, with duration and dose adjusted to stage, renal function, age and toxicity.

Confirm DPD status and monitor marrow, renal function, diarrhoea, mucositis, hand–foot syndrome, thrombosis and acute and cumulative neuropathy; stop capecitabine and seek advice for significant early toxicity.

Uses the high neoantigen burden of mismatch-repair-deficient tumour to produce durable immune-mediated control in many eligible patients.

Pembrolizumab for eligible dMMR or MSI-high disease

Give pembrolizumab 200 mg intravenously every 3 weeks or 400 mg every 6 weeks within the licensed and current NICE-funded line for unresectable or metastatic mismatch-repair-deficient or MSI-high colorectal cancer.

Monitor for immune lung, bowel, liver, endocrine, renal, cardiac, skin and neurological toxicity and distinguish immune colitis from infection or obstruction before immunosuppression.

Blocks EGFR signalling in molecularly eligible colorectal cancer, particularly left-sided disease in the appropriate treatment line.

Cetuximab for selected RAS wild-type disease

Use the licensed intravenous schedule, commonly 500 mg/m² every 2 weeks with the selected chemotherapy, only for the precise RAS wild-type, tumour-side and current funded metastatic indication.

Confirm extended RAS status and review BRAF and side; monitor infusion reaction, acneiform rash, diarrhoea, magnesium and infection and provide proactive skin care.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Obstruction and perforation

Circumferential narrowing, intussusception or tumour necrosis can obstruct or perforate, causing ischaemia, peritonitis, sepsis and emergency stoma formation.

Bleeding and iron deficiency

Chronic mucosal blood loss causes fatigue and microcytic anaemia, while ulcerated tumour can produce overt haemorrhage and transfusion need.

Local pelvic morbidity

Rectal or recurrent tumour causes pain, tenesmus, fistula, hydronephrosis, sexual and urinary dysfunction and sacral or nerve invasion.

Distant metastatic disease

Liver, lung, peritoneal and less common bone or brain deposits cause organ failure, ascites, obstruction, pain and cachexia.

Treatment and stoma morbidity

Leak, abscess, ileus, low anterior resection syndrome, neuropathy, diarrhoea, hand–foot syndrome, sexual dysfunction and stoma problems affect recovery.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

After resection, review wound, ileus, leak, abscess, VTE, nutrition, bowel function, urinary and sexual outcomes and stoma viability and output.
During oxaliplatin and fluoropyrimidine treatment, monitor blood counts, renal and liver function, diarrhoea, mucositis, hand–foot syndrome, infection and cumulative neuropathy before every cycle.
Use the NICE surveillance schedule after curative treatment with clinical review, CEA where informative and interval CT and colonoscopy, tailoring to stage and fitness for salvage.
After rectal treatment, monitor low anterior resection syndrome, pelvic pain, bowel urgency, continence, urinary and sexual function and stoma reversal readiness.
A watch-and-wait programme requires frequent digital rectal examination, endoscopy, rectal MRI and systemic surveillance; loss of response triggers prompt salvage assessment.
Track family-history and MMR-reflex actions to completion, including germline counselling and cascade colonoscopic prevention when Lynch is confirmed.
Investigate rising CEA with appropriate imaging but do not treat the marker alone, and investigate symptoms even when CEA remains normal.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

FIT triages rather than absolves

Faecal haemoglobin improves pathway efficiency, but sampling variation and non-bleeding tumours mean persistent high-risk clinical concern still needs investigation.

Rectal MRI changes the operation before theatre

A threatened mesorectal margin or sphincter relationship can be improved by neoadjuvant treatment only if recognised on a high-quality baseline scan.

Stage IV can remain curable

Limited liver or lung metastases may undergo complete resection or ablation, so specialist resectability review should precede a palliative label.

MMR testing has three roles

It informs Lynch screening, stage-II prognostic and chemotherapy discussion and immune-treatment sensitivity in advanced disease.

A complete response is not no cancer

Watch-and-wait substitutes intensive surveillance and timely salvage for immediate rectal surgery; it is not routine discharge after a good scan.

Neuropathy can outlast cure

Oxaliplatin benefit must be balanced against cumulative sensory damage, especially when absolute adjuvant benefit is modest and symptoms are emerging.

11Common pitfallsFrequent interpretation and management errors.

01
Explaining iron-deficiency anaemia with diet or haemorrhoids without colorectal investigation.
02
Using a low FIT as an absolute cancer exclusion despite a mass, persistent symptoms or iron deficiency.
03
Performing an incomplete colonoscopy without arranging completion imaging for synchronous disease.
04
Staging rectal cancer from CT alone without dedicated high-resolution pelvic MRI.
05
Treating all stage II colon cancer with chemotherapy without MMR and pathological-risk review.
06
Calling liver metastases unresectable without specialist hepatobiliary MDT assessment.
07
Starting EGFR treatment before extended RAS and tumour-side review.
08
Using CEA alone to diagnose recurrence or to reassure a symptomatic patient.
09
Calling watch-and-wait absence of treatment and failing to deliver intensive local surveillance.
10
Planning rectal treatment without stoma, bowel, urinary, sexual and fertility counselling.