Phys · gastrointestinal
Colorectal Cancer
Also known as colorectal cancer · CRC · colon cancer · rectal cancer · bowel cancer · colorectal carcinoma · adenoma-carcinoma sequence · APC · KRAS · TP53 · microsatellite instability · Lynch syndrome · hereditary nonpolyposis colorectal cancer · HNPCC · familial adenomatous polyposis · FAP · faecal immunochemical test · FIT · total mesorectal excision · TME · FOLFOX · CAPOX · FOLFIRI · cetuximab · panitumumab · bevacizumab · pembrolizumab · CEA
Consultant-physician guide to colorectal cancer — the third most common cancer worldwide, whose prevention rests on the adenoma-carcinoma sequence and whose treatment hangs on TNM/Dukes staging. Covers the molecular pathway (APC, KRAS, TP53 and the microsatellite instability/Lynch pathway), risk factors (age, family history, IBD, diet, the hereditary syndromes), FIT-based screening and surveillance intervals, clinical presentation by tumour site, the surgical principles (colectomy with lymph node dissection, total mesorectal excision for rectal cancer), adjuvant chemotherapy by stage (FOLFOX/CAPOX for stage III, selective stage II), metastatic management (chemotherapy plus biologic by RAS/MSI status, metastasectomy, pembrolizumab for MSI-high), and the hereditary syndromes (Lynch, FAP, MUTYH, Peutz-Jeghers, juvenile polyposis). Structured for FRACP DWE and DCE, MRCP, and ABIM preparation.
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Red flags
- Any new rectal bleeding in a patient over 40 (or with weight loss, anaemia, or change in bowel habit) is colorectal cancer until proven otherwise — never dismiss it as haemorrhoids without endoscopy
- Iron deficiency anaemia in an older man or a postmenopausal woman is a right-sided colorectal cancer until excluded — investigate, do not just prescribe iron
- A change in bowel habit to looser stools or increased frequency persisting over 6 weeks in a patient over 50 needs colonoscopy
- Large bowel obstruction in an older adult — a left-sided cancer is the commonest cause; resuscitate and image urgently
- Universal MMR and MSI testing on every new colorectal cancer — screens for Lynch syndrome (family implications) and identifies immunotherapy candidates; omitting it is a serious error
- A palpable right iliac fossa mass or hepatomegaly with weight loss — locally advanced or metastatic disease
- Colorectal cancer under age 50 — rising incidence; always exclude a hereditary syndrome with genetic testing
Colorectal Cancer
Meet the patient
A 67-year-old man presents to his GP with six weeks of looser, more frequent stools and a dragging sensation in his left lower quadrant. His bloods show a haemoglobin of 98 with a ferritin of 12 — iron deficiency. The GP reaches for iron tablets and a diagnosis of dietary lack.[1]
That single move — treating the number without finding the source — is how a left-sided colon cancer becomes an emergency obstruction six months later. The two questions that anchor everything below: where is the tumour? (the site dictates the symptom) and what stage and molecular profile? (they dictate every treatment decision).[1]
References10ShowHide
- [1]Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA Cancer J Clin, 2024.PMID 38572751
- [2]Fearon ER, Vogelstein B A genetic model for colorectal tumorigenesis Cell, 1990.PMID 2188735
- [3]Boland CR, Goel A Microsatellite instability in colorectal cancer Gastroenterology, 2010.PMID 20420947
- [4]Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study N Engl J Med, 1993.PMID 8474513
- [5]Bretthauer M, Løberg M, Wieszczy P, et al. Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death N Engl J Med, 2022.PMID 36214590
- [6]André T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer N Engl J Med, 2004.PMID 15175436
- [7]Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer N Engl J Med, 2004.PMID 15175435
- [8]Karapetis CS, Khambata-Ford S, Jonker DJ, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer N Engl J Med, 2008.PMID 18946061
- [9]Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer N Engl J Med, 2004.PMID 15496622
- [10]André T, Shiu KK, Kim TW, et al. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer N Engl J Med, 2020.PMID 33264544