Lucan · Conditions

Colorectal cancer

Australian guidance: Cancer Council Australia Clinical Practice Guidelines for Colorectal Cancer + NBCSP

1. Definition and epidemiology

Colorectal cancer (CRC) is a malignant neoplasm arising from the epithelial lining of the colon or rectum, with over 95% of cases being adenocarcinomas. In Australia, CRC is the second most commonly diagnosed cancer and the second leading cause of cancer death, with approximately 15,500 new cases diagnosed annually. Incidence increases steeply after age 50 and risk is influenced by family history, diet, inflammatory bowel disease, and lifestyle factors including physical inactivity, obesity, and alcohol use.

2. Pathophysiology

Most CRCs arise through one of two well characterised molecular pathways described in Robbins Ch 17. The chromosomal instability pathway accounts for approximately 80% of sporadic cases and involves stepwise accumulation of mutations beginning with APC loss, which releases beta-catenin from degradation and drives aberrant Wnt signalling. Subsequent mutations in KRAS, SMAD2/4, and TP53 drive progression from normal mucosa through low-grade adenoma to high-grade adenoma and ultimately invasive carcinoma over roughly 10 to 15 years. The microsatellite instability pathway, responsible for most hereditary nonpolyposis colorectal cancer (Lynch syndrome) and a proportion of sporadic cases, results from defective mismatch repair (MLH1, MSH2, MSH6, PMS2), generating hypermutated tumours that paradoxically carry a better prognosis stage for stage. Up to 5% of CRCs are specifically inherited through familial adenomatous polyposis (FAP, APC germline mutation) or Lynch syndrome, and up to 25% have some hereditary contribution. Serrated adenomas represent a third pathway involving BRAF mutation and CpG island methylation.

3. Clinical presentation and diagnostic criteria

Presentation depends on tumour location. Right-sided colonic tumours grow large before causing symptoms and typically present with occult bleeding, iron deficiency anaemia, and fatigue. Left-sided and sigmoid tumours more often cause change in bowel habit (alternating loose stools and constipation), haematochezia, tenesmus, or a palpable abdominal mass. Rectal cancers classically present with fresh rectal bleeding, mucus per rectum, and a sensation of incomplete evacuation. Red flag symptoms warranting urgent investigation include positive immunochemical faecal occult blood test (iFOBT), unexplained iron deficiency anaemia, passage of blood with or without mucus, change in bowel habit lasting more than six weeks, unexplained abdominal mass, or unexplained weight loss. Digital rectal examination is a mandatory component of the initial physical examination. Emergencies including obstruction, perforation, or acute haemorrhage occur in a minority but require prompt surgical assessment.

4. Investigations and AU-specific cutoffs

Initial workup at GP level includes full blood count (looking for iron deficiency anaemia), iron studies, liver function tests, and a digital rectal examination. Colonoscopy is the gold standard diagnostic investigation and should be completed within four weeks when symptoms suggest CRC.

Staging investigations for confirmed CRC include CT of the chest, abdomen, and pelvis; MRI liver for hepatic metastases; and PET-CT where indicated. For rectal cancer, endorectal ultrasound and dedicated pelvic MRI assess depth of invasion and mesorectal nodal status, which are critical for planning neoadjuvant therapy. Investigations should be completed within two weeks of confirmed diagnosis. Carcinoembryonic antigen (CEA) is measured at baseline as a monitoring marker, though it has poor sensitivity for early disease. Molecular testing for KRAS, NRAS, BRAF, and mismatch repair status is performed on tumour tissue to guide systemic therapy choices.

National Bowel Cancer Screening Program (NBCSP) cutoffs: - Category 1 (near average risk): iFOBT every two years from age 45 to 74; a positive iFOBT triggers high-quality diagnostic colonoscopy. - Category 2 (moderately increased risk, e.g., one first-degree relative with CRC or advanced adenoma): colonoscopy every five years starting 10 years before the earliest diagnosis in a first-degree relative, or from age 50, whichever is earlier, to age 74. - Category 3 (high risk, e.g., two or more first-degree relatives or Lynch syndrome): colonoscopy every five years from 10 years before the earliest family diagnosis or age 40, whichever is earlier, to age 74.

Post-polypectomy surveillance intervals are governed by the Cancer Council Australia Colonoscopy Surveillance guidelines (NHMRC approved 2018). Low risk adenomas (1 to 2 tubular adenomas less than 10 mm) warrant repeat colonoscopy at five years; high risk adenomas (3 or more adenomas, or any adenoma 10 mm or larger, or any villous or high-grade dysplasia) warrant surveillance at three years.

5. Management

Treatment planning is guided by a multidisciplinary team (MDT) meeting, which should occur within two weeks of diagnosis and staging, and which should include surgical, medical, and radiation oncology.

Surgery is the primary curative modality for non-metastatic disease and is recommended for the majority of patients. Colonic resection should be performed within five weeks of MDT discussion when no neoadjuvant therapy is required. For rectal cancer, neoadjuvant long-course chemoradiation (standard for locally advanced high-risk rectal tumours) or short-course radiotherapy is followed by surgery eight to twelve weeks later. Total mesorectal excision (TME) is the standard surgical technique for rectal cancer and requires surgeons with appropriate qualifications and expertise.

Adjuvant chemotherapy is indicated for patients with stage III (node positive) colon cancer and for selected high-risk stage II patients; it should commence within eight weeks of surgery. Neoadjuvant and adjuvant systemic therapy and radiation should begin within three weeks of the MDT decision. For metastatic CRC, treatment is not curative in most cases but can improve quality of life and survival. Early referral to palliative care is recommended and should be based on need rather than prognosis.

6. Pharmacology and AU PBS notes

Adjuvant chemotherapy for stage III colon cancer: - FOLFOX (oxaliplatin + fluorouracil + leucovorin folinic acid) is the standard six-month regimen; three-month CAPOX (oxaliplatin + capecitabine) is an acceptable alternative in low-risk stage III disease with reduced neurotoxicity. - Capecitabine (Xeloda) alone is used for patients unsuitable for oxaliplatin-based therapy.

Metastatic CRC first-line systemic therapy: - FOLFOX or FOLFIRI (fluorouracil + leucovorin + irinotecan) form the chemotherapy backbone. - Bevacizumab (Avastin, anti-VEGF) is added for RAS wild-type or mutant tumours; PBS Section 100 (Highly Specialised Drugs) applies. - Cetuximab (Erbitux, anti-EGFR) or panitumumab (Vectibix) are used for RAS and BRAF wild-type left-sided tumours; PBS streamlined authority required with RAS wild-type status confirmed on tumour tissue. - BRAF V600E mutant mCRC: encorafenib plus cetuximab is the standard second-line regimen. - MSI-H/dMMR mCRC: pembrolizumab (Keytruda) is PBS-listed first-line; streamlined authority applies with confirmed mismatch repair deficiency. - Trifluridine/tipiracil (Lonsurf) is third-line PBS-listed for refractory mCRC.

7. Complications and monitoring

Key complications include bowel obstruction (presenting acutely or subacutely), perforation with peritonitis, haemorrhage, fistula formation, and distant metastasis (most commonly hepatic and pulmonary). Treatment-related complications include anastomotic leak following resection, radiation proctitis, peripheral neuropathy and bone marrow suppression from oxaliplatin-based regimens, and stoma-related issues.

Post-treatment surveillance per the optimal care pathway: - Clinical review and CEA every three to six months for the first two years, then six monthly to five years. - CT chest, abdomen, and pelvis at twelve months and again at twenty-four to thirty-six months post-resection in patients fit for further treatment. - Colonoscopy at twelve months post-resection (or at twelve months after the pre-operative colonoscopy if complete pre-operative colonoscopy was performed), then three yearly if normal, to detect metachronous tumours and anastomotic recurrence. - Most recurrent disease is detected via routine follow-up or by the patient presenting with symptoms; any suspected recurrence should prompt prompt re-entry into specialist care for restaging.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.