• Colorectal cancer trials open today (registry snapshot): Every phase 2 or 3 interventional trial that was recruiting, about to open or still running for colorectal, colon or rectal cancer on ClinicalTrials.gov in September 2026, with the hospitals in the United Kingdom that take part named where the registry lists them.
• Complete response: All detectable signs of the tumour have vanished on scans and examination after treatment.
• Colorectal cancer drugs in England: what NICE has recommended: Which bowel cancer drugs the NHS in England funds, and which it does not.
• Colorectal cancer: the failed and stopped programmes, and why: The list of treatments that looked right and did not work: EGFR antibodies after surgery, heated chemotherapy washes of the abdomen, immunotherapy in ordinary bowel cancer, and treating a positive blood test before a scan shows anything.
• Living with FOLFOX, CAPOX, FOLFIRI and the EGFR antibodies: The bowel cancer regimens share low blood counts, tiredness, sickness and a sore mouth.
• Rash and skin toxicity (acneiform rash, paronychia): Skin reactions from cancer drugs, ranging from the acne-like rash that nearly everyone on an EGFR inhibitor gets (a sign the drug is working) to painful nail-fold infections, itching, and rare severe blistering reactions.
• Sexual function, fertility and body image after bowel cancer: Pelvic surgery and radiotherapy can affect the nerves and tissues that control erections, ejaculation, vaginal comfort and sensation, and pelvic radiotherapy often causes infertility and an early menopause.
• Living with a stoma after bowel cancer surgery: A colostomy or ileostomy after bowel cancer surgery may be temporary, to let a join heal, or permanent.
• Lynch syndrome testing after bowel cancer, and what it means for the family: Every bowel cancer should be tested for mismatch repair loss, and where it is found, for whether that loss is inherited.
• Low anterior resection syndrome (LARS): The group of bowel problems that can follow sphincter-preserving surgery for rectal cancer: going more often, urgency with or without leaking, feeling the bowel is not empty, passing small amounts little and often, and not being able to tell wind from stool.

Diagnosis and staging (UK pathway): Quantitative faecal immunochemical testing in primary care to decide referral; colonoscopy with biopsy, or computed tomography colonography where colonoscopy is not possible; computed tomography of chest, abdomen and pelvis for everyone and high-resolution pelvic magnetic resonance imaging for every rectal cancer; RAS and BRAF V600E testing in metastatic disease before systemic therapy; mismatch repair testing at diagnosis, which also finds Lynch syndrome; baseline carcinoembryonic antigen.

Biomarker results to ask for: RAS (KRAS and NRAS exons 2-4) for anti-EGFR eligibility, BRAF V600E, MMR/MSI status (universal testing at diagnosis), HER2 amplification (IHC/ISH or NGS), Primary tumour sidedness, NTRK fusions (rare), POLE/POLD1 (ultramutated, IO-responsive), ctDNA MRD after surgery (Signatera, Guardant Reveal), CEA (monitoring), UGT1A1*28 (irinotecan dosing) and DPYD (fluoropyrimidine toxicity), Germline testing for Lynch when dMMR or young onset, APC inactivating mutation (wnt pathway gatekeeper): 58-77%, TP53 mutation (with 17p loss): 52-73%, KRAS activating mutation (any allele): 40-44%, KRAS G12D g12d allele (share of kras mutation records): 27-29%, KRAS G12V g12v allele (share of kras mutation records): 16-22%, KRAS G13D g13d allele (share of kras mutation records): 16-24%, KRAS G12C g12c allele (share of kras mutation records): 6-9%, KRAS outside exon 2 codon 59, 61, 117 or 146 mutation (share of kras missense records): 16-18%, NRAS activating mutation (codon 12, 13, 59, 61 or 117): 4-9%, BRAF V600E v600e mutation: 6-18%, BRAF non-V600 class ii and class iii mutations (d594, g466, g469, k601, n581) and fusions: 2-4%, PIK3CA hotspot mutation (e542k, e545k, h1047r): 20-28%, SMAD4 mutation or deep deletion (18q loss): 12-16%, FBXW7 inactivating mutation: 13-17%, ERBB2 (HER2) high-level amplification: 2-3%, ERBB2 mutation activating mutation (not amplification): 4-6%, MSI-high / dMMR microsatellite instability or mismatch repair deficiency: 5-15%, POLE exonuclease (proofreading) domain hotspot mutation, ultramutated tumours: 0.7-2%, POLD1 exonuclease domain hotspot mutation; germline p.ser478asn: 0.03%, Tumour mutational burden 10 or more mutations per megabase (panel): 15-19%, Chromosomal instability (CIN) aneuploidy with 18q, 17p and 8p loss and 8q, 13q and 20q gain: 84%, RNF43 inactivating mutation (g659fs hotspot): 5-12%, RSPO2 / RSPO3 gene fusion (ptprk-rspo3, eif3e-rspo2): 0.4-10%, CTNNB1 activating mutation or large in-frame deletion: 5-7%, AMER1 (FAM123B) inactivating mutation: 6-13%, SOX9 inactivating mutation: 10-12%, ARID1A inactivating mutation: 9-13%, TGFBR2 frameshift of the polyadenine coding microsatellite: 3-10%, B2M inactivating mutation or deletion (antigen presentation): 3-7%, TCF7L2 mutation or vti1a-tcf7l2 fusion: 7-15%, MYC high-level amplification (8q24): 4-5%, IGF2 high-level amplification with overexpression: 2%, EGFR high-level amplification (and acquired ectodomain mutation): 1-2%, NTRK1 / NTRK3 gene fusion (lmna-ntrk1, etv6-ntrk3): 0.2-0.3%, RET gene fusion (ncoa4-ret, ccdc6-ret): 0.1%, ALK gene fusion: 0.1%, PTEN inactivating mutation or deep deletion: 6-8%, BCL9L, RBM10, CTCF, KLF5 recurrently mutated genes found only in the large prospective exome cohort: 7%, Faecal haemoglobin by quantitative faecal immunochemical test: 10 micrograms per gram of faeces refers a symptomatic patient in England, 120 micrograms per gram calls a screened person for colonoscopy, Circumferential resection margin on rectal magnetic resonance imaging before surgery and on the specimen after it (1 mm rule), Extramural venous invasion on rectal magnetic resonance imaging.

Scans and tests linked to this cancer: CEA surveillance after colorectal cancer surgery, Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood), Companion diagnostics, Comprehensive genomic profiling, CT (computed tomography), Cytogenetics and FISH.

Bring copies of scan reports, pathology and blood results, and a list of every medicine and supplement.

• Prevention and chemoprevention: Remove adenomas at colonoscopy and put the person on a surveillance interval set by what was found; consider daily aspirin for more than two years in Lynch syndrome. Population screening from 50 in England and 45 in the United States. Diet, weight, alcohol, smoking and physical activity account for the 54 percent of UK cases Cancer Research UK judges preventable. (Surveillance intervals after polypectomy, Polyp types in the bowel, Aspirin for cancer prevention and adjuvant therapy, Lynch syndrome, Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood), Exercise & lifestyle oncology)
• Chemotherapy after surgery for stage 2 and stage 3, and how the benefit is worked out: Chemotherapy after the operation is given to kill cells that have already left the bowel but are too few to see, and the whole decision is about how large that risk is against what the treatment costs you. For stage 3 (cancer in the lymph nodes), NICE NG151 is explicit and the same for colon and for rectal cancer treated with short-course radiotherapy or no preoperative treatment: offer capecitabine with oxaliplatin (CAPOX) for 3 months, or if that is not suitable either oxaliplatin with fluorouracil and folinic acid (FOLFOX) for 3 to 6 months, or a single-agent fluoropyrimidine such as capecitabine for 6 months. It then says to base the choice on the person's histopathology (giving pT1 to T3 with pN1 against pT4 or pN2 as the example), performance status, personal preferences, comorbidities and age, which is the guideline's way of saying that three months of a doublet and six months of a single tablet are both defensible and the balance is yours to weigh. For stage 2 (no nodes involved) NICE NG151 makes no adjuvant recommendation at all, so the conversation runs on individual risk features, on the mismatch repair result, and increasingly on whether circulating tumour DNA is detectable after surgery; the ctDNA-guided studies on this record (DYNAMIC and the others) are where that question is being settled, and a trial is a reasonable answer. Two practical points NICE puts in writing: monitor prolonged sensory symptoms after platinum chemotherapy, because they are a sign the dose needs reducing to prevent permanent neuropathy, and a DPD blood test comes before fluorouracil or capecitabine because low DPD raises the risk of severe toxicity. The OnCo decision aid at /tools/colorectal-adjuvant-chemotherapy/ lays the NICE wording out by site, stage and fitness for oxaliplatin. (CAPOX (capecitabine, oxaliplatin), FOLFOX (5-FU, leucovorin, oxaliplatin), Capecitabine, Oxaliplatin, Circulating tumour DNA (ctDNA), DYNAMIC)
• Rectal cancer: surgery or chemoradiotherapy first, and watch and wait if the tumour disappears: Rectal cancer is the part of bowel cancer where the order of treatment is a real choice. NICE NG151 says not to offer preoperative radiotherapy for early rectal cancer (cT1 to T2, cN0, M0) outside a clinical trial, and to offer preoperative radiotherapy or chemoradiotherapy where the cancer is cT1 to T2 with involved nodes, or cT3 to T4 with any node status. Two forms are used: a short course of radiotherapy on its own, and a longer course of radiotherapy given together with chemotherapy (Macmillan says the drug most commonly used is capecitabine tablets, started on the first morning of radiotherapy and taken throughout it, with a DPD test first), and in recent practice both are often followed by several months of chemotherapy before surgery (total neoadjuvant therapy, tested in RAPIDO, PRODIGE 23 and OPRA on this record; PROSPECT asked the opposite question, whether chemotherapy alone can replace radiotherapy in selected tumours). The reason this matters to a patient is that treatment before surgery shrinks the tumour, improves the chance of a clear margin, and in a minority makes the tumour disappear altogether on examination, MRI and endoscopy. NICE NG151 covers that case directly: inform people with a complete clinical and radiological response who wish to defer surgery that there is a risk of recurrence, and that there are no prognostic factors to guide selection for deferral; for those who choose to defer, encourage participation in a clinical trial and ensure data is collected via a national registry. Watch and wait is therefore not less treatment but a different commitment, to frequent examination and scans for years. For early rectal cancer NICE offers a shared decision between transanal excision, endoscopic submucosal dissection and total mesorectal excision, and gives a table comparing them on exactly the points a patient asks about: whether bowel is removed, whether a stoma is possible, hospital stay, scarring and the complications of each. (Total neoadjuvant therapy (TNT, rectal cancer), Organ preservation (watch-and-wait, bladder-sparing, larynx preservation), Total mesorectal excision (TME), RAPIDO, PRODIGE 23, OPRA, PROSPECT (Alliance N1048), CAO/ARO/AIO-94 (German Rectal Cancer Study))
• Surgery or ablation when the cancer has spread to the liver: Bowel cancer that has spread to the liver is one of the few settings in which surgery for metastatic disease is done with the intention of cure, and a meaningful number of people live many years after it. NICE NG151 says to consider resection, either simultaneous with the bowel operation or sequential, after discussion by a multidisciplinary team with expertise in resection of disease in all involved sites, and to consider perioperative systemic anticancer therapy where liver resection is a suitable treatment. Where the liver disease is not resectable, it says to consider chemotherapy with local ablative techniques after discussion by a specialist multidisciplinary team, and not to offer selective internal radiation therapy as first-line treatment for liver metastases unsuitable for local treatment except under the arrangements its HealthTech guidance sets out. The same logic extends to the lungs: consider metastasectomy, ablation or stereotactic body radiation therapy for lung metastases suitable for local treatment, after discussion by a team including a thoracic surgeon and a specialist in non-surgical ablation, and consider a biopsy for a single lung lesion to exclude a primary lung cancer. For disease limited to the peritoneum, NICE says to offer systemic therapy and, within the multidisciplinary team, to discuss referral to a nationally commissioned specialist centre to consider cytoreductive surgery with heated intraperitoneal chemotherapy. The practical consequence for a patient is that the answer to whether an operation is possible depends on which team is looking, so asking whether a specialist liver or peritoneal unit has seen the scans is a fair question, and a second opinion is a recognised step (Bowel Cancer UK has a page on it). (Hepatectomy (liver resection), Thermal ablation (RFA, microwave, cryo), Microwave and radiofrequency ablation systems, Liver-directed therapy (TACE, TARE, HAI, ablation), HIPEC / PIPAC (intraperitoneal chemotherapy), SABR-COMET: stereotactic ablative radiotherapy for oligometastatic cancer)
• Stage I and low-risk stage II colon cancer: Resection with complete mesocolic excision and at least twelve lymph nodes examined; observation afterwards. Adjuvant chemotherapy is not given for stage I. In stage II the absolute gain from fluorouracil and folinic acid is small: QUASAR (3,239 patients, 2,963 with stage II disease) found a relative risk of death of 0.82 and of recurrence 0.78, translating to about 3.6 percent absolute survival. DYNAMIC showed that a negative circulating tumour DNA result four to seven weeks after surgery identifies patients who can safely have no chemotherapy, cutting adjuvant use from 27.9 to 15.3 percent without worse recurrence-free survival. Mismatch-repair deficient stage II disease gains nothing from fluorouracil alone and is observed. (QUASAR, DYNAMIC, MRD / molecular residual disease testing, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), CEA surveillance after colorectal cancer surgery)
• Circulating tumour DNA after surgery: A tumour-informed assay four to seven weeks after resection is the strongest single predictor of recurrence: GALAXY within CIRCULATE-Japan and DYNAMIC-III both show a large separation (DYNAMIC-III three-year recurrence-free survival 87 percent if negative against 49 percent if positive). De-escalation on a negative result is proven only in stage II (DYNAMIC, adjuvant chemotherapy use 15.3 against 27.9 percent with equal recurrence-free survival); in stage III, DYNAMIC-III could not show non-inferiority. Escalation on a positive result has failed twice: ALTAIR missed its disease-free survival endpoint (9.30 against 5.55 months, hazard ratio 0.79, p=0.107) and DYNAMIC-III's escalation arm gave no benefit. CIRCULATE-US (NRG-GI008) and TRACC are the trials still running. (DYNAMIC, DYNAMIC-III, ALTAIR, CIRCULATE-Japan (GALAXY / VEGA / ALTAIR), CIRCULATE-US, BESPOKE CRC, TRACC, MRD / molecular residual disease testing, Minimal / molecular residual disease (MRD), Circulating tumour DNA (ctDNA))
• Palliation: liver capsule pain, pelvic symptoms and early palliative care: Liver capsule pain from bulky metastases is a position-dependent right upper quadrant pain that usually responds to dexamethasone and, when it does not, to a short course of palliative radiotherapy to the liver. Bleeding, discharge and pain from an unresectable rectal tumour respond to hypofractionated palliative radiotherapy; tenesmus is the hardest symptom and may need a nerve block or a stoma. Opioids are titrated with laxatives, and anaemia from chronic blood loss is treated with iron or transfusion. Early integrated palliative care alongside oncology from the diagnosis of incurable disease is recommended, and dietetic review matters where a stoma or short bowel follows surgery. (Palliation in colorectal cancer: obstruction, stents, stomas and liver capsule pain, Palliative radiotherapy, Early integrated palliative care, Transfusion support and anaemia management)
• Follow-up after potentially curative surgery: Follow up for detection of local recurrence and distant metastases for the first three years, including serum carcinoembryonic antigen and computed tomography of the chest, abdomen and pelvis; a clearance colonoscopy at one year and a surveillance colonoscopy three years after that. (CEA surveillance after colorectal cancer surgery, CT (computed tomography), Colonoscopy, Surveillance intervals after polypectomy)
• High-risk stage II colon cancer: Resection then a discussion about three to six months of a fluoropyrimidine with or without oxaliplatin, weighing T4 disease, obstruction or perforation, fewer than twelve nodes examined, lymphovascular or perineural invasion and poor differentiation against the neuropathy risk. SCOT included high-risk stage II patients and found three months of oxaliplatin-containing chemotherapy non-inferior to six (three-year disease-free survival 76.7 against 77.1 percent) with grade 2 or worse neuropathy halved. Mismatch-repair deficiency remains a reason not to give fluorouracil alone. (SCOT, QUASAR, FOLFOX (5-FU, leucovorin, oxaliplatin), CAPOX (capecitabine, oxaliplatin), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR))
• Stage III colon cancer, mismatch-repair proficient: Resection then adjuvant oxaliplatin-fluoropyrimidine chemotherapy. MOSAIC established it (three-year disease-free survival 78.2 against 72.9 percent with fluorouracil alone, hazard ratio 0.77; six-year overall survival gain confined to stage III). Duration follows IDEA: three months of CAPOX for T1-3 N1 disease (three-year disease-free survival 83.1 against 83.3 percent for six months) and six months of FOLFOX or CAPOX for T4 or N2. Cetuximab must not be added: N0147 and PETACC-8 both found no benefit and more toxicity. (MOSAIC, IDEA collaboration, SCOT, TOSCA, FOLFOX (5-FU, leucovorin, oxaliplatin), CAPOX (capecitabine, oxaliplatin), Alliance N0147, PETACC-8)
• Stage III colon cancer, mismatch-repair deficient: Resection then FOLFOX with atezolizumab for twelve months (ATOMIC, three-year disease-free survival 86 against 77 percent), the first adjuvant immunotherapy success in colorectal cancer. Neoadjuvant nivolumab with ipilimumab is the alternative under test: NICHE-2 produced a 68 percent pathological complete response rate and AZUR-2 (NCT05855200, 892 patients, primary completion March 2029) is the phase 3 that would make perioperative dostarlimab standard. (ATOMIC (Alliance A021502), NICHE-2, Study of Perioperative Dostarlimab in Participants With Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer, Atezolizumab, FOLFOX (5-FU, leucovorin, oxaliplatin), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR))
• Locally advanced operable colon cancer: chemotherapy before surgery: Six weeks of preoperative oxaliplatin-fluoropyrimidine chemotherapy followed by surgery and eighteen weeks more is an option for radiologically staged T3 with deep invasion or T4 disease. FOxTROT (1,053 patients) found residual or recurrent disease within two years in 16.9 against 21.5 percent with surgery first (rate ratio 0.72), with fewer serious postoperative complications and 4.3 percent needing expedited surgery for obstruction. Panitumumab added nothing and mismatch-repair deficient tumours gained little, so they are better served by neoadjuvant immunotherapy in a trial. (FOxTROT, FOLFOX (5-FU, leucovorin, oxaliplatin), CAPOX (capecitabine, oxaliplatin), NICHE-2)
• Locally advanced rectal cancer: radiotherapy and total neoadjuvant therapy: Total mesorectal excision is the operation (Dutch TME trial) and preoperative rather than postoperative radiotherapy is the sequence (CAO/ARO/AIO-94: five-year local relapse 6 against 13 percent, no survival difference). High-risk disease (cT4, extramural vascular invasion, cN2, threatened mesorectal fascia, lateral nodes) is treated with total neoadjuvant therapy: short-course 5 x 5 Gy then CAPOX or FOLFOX before surgery (RAPIDO: three-year disease-related treatment failure 23.7 against 30.4 percent, hazard ratio 0.75; STELLAR: three-year disease-free survival 64.5 against 62.3 percent) or long-course chemoradiotherapy with FOLFIRINOX before it (PRODIGE 23: three-year disease-free survival 76 against 69 percent, hazard ratio 0.69). Delaying surgery four to eight weeks after short-course radiotherapy is safe (Stockholm III). For sphincter-sparing candidates who do not need radiotherapy, PROSPECT showed neoadjuvant FOLFOX with selective chemoradiotherapy is non-inferior (five-year disease-free survival 80.8 against 78.6 percent). (Dutch TME trial, CAO/ARO/AIO-94 (German Rectal Cancer Study), RAPIDO, PRODIGE 23, STELLAR (rectal cancer), Stockholm III, PROSPECT (Alliance N1048), Total neoadjuvant therapy (TNT, rectal cancer), IMRT / IGRT (modern external beam), Chemoradiation (chemoradiotherapy, CRT))
• The operation and what a stoma means: temporary or permanent: Removing the cancer with a rim of healthy bowel, and joining the two ends back together, is what cures most bowel cancer. The operation depends on where the tumour sits. Macmillan names the colon operations as a right or left hemi-colectomy, a sigmoid colectomy (also called a high anterior resection), a transverse colectomy or a total colectomy, and the rectal ones as a local excision for a very small stage 1 cancer, an anterior resection or low anterior resection for the upper or middle rectum, usually with a total mesorectal excision, and it says that if the cancer is very low in the rectum and close to the anus you are more likely to need a permanent stoma. NICE NG151 recommends laparoscopic (keyhole) resection as an alternative to open resection for both colon and rectal cancer when both are suitable, says to consider open surgery for locally advanced tumours or after previous abdominal or pelvic surgery, and to use robotic surgery only within established programmes with audited outcomes. It sets volume floors for rectal surgery: at least 10 major resections a year per hospital and at least 5 per surgeon. On the stoma, NICE asks teams to advise people of the likelihood of having one, why it might be necessary and for how long it might be needed, and to have a trained stoma professional provide information on care and on learning to live with it. Bowel Cancer UK puts it plainly: a reversible stoma is formed to let the join heal and a permanent one when the two ends cannot be joined, and the surgeon may not know for certain until the operation has started. A colostomy is formed from the large bowel and the output is more solid; an ileostomy is formed from the small bowel, the output is looser and more fluid and salt are lost. The NHS says recovery from a colostomy usually takes about 8 weeks, with no heavy lifting in that time, and that permanent colostomy supplies come free on prescription. Prehabilitation before the operation and an enhanced recovery programme after it are both worth asking about: NICE says to explain what recovery protocols involve and their value, and Bowel Cancer UK says prehabilitation reduces anxiety, improves fitness and can shorten the stay. (Colectomy, Total mesorectal excision (TME), Stoma (colostomy, ileostomy, urostomy), Prehabilitation before cancer surgery, Enhanced recovery (ERAS) and perioperative nutrition)
• Which first treatment when the cancer has spread, by RAS, BRAF, mismatch repair and which side of the bowel: When bowel cancer has spread, the first treatment is chosen by three test results and one piece of anatomy. NICE NG151 says to test for RAS and BRAF V600E mutations in all people with metastatic colorectal cancer suitable for systemic anticancer treatment, and separately recommends immunotherapy where the tumour is MSI-high or mismatch repair deficient. If RAS is wild-type, NICE recommends cetuximab or panitumumab with FOLFOX or FOLFIRI; if RAS is mutated, those antibodies do not work and bevacizumab with fluoropyrimidine-based chemotherapy is recommended where targeted treatment or immunotherapy is unsuitable. The anatomy is sidedness: cancers that start on the left (descending colon, sigmoid, rectum) respond better to the EGFR antibodies than cancers that start on the right, which is why the standard-of-care rows put anti-EGFR treatment with left-sided RAS wild-type disease and bevacizumab with right-sided or RAS-mutant disease (PARADIGM tested that question head to head; CRYSTAL and FIRE-3 are the older comparisons). BRAF V600E is its own group, with encorafenib and cetuximab added to chemotherapy (BREAKWATER). What this means at the appointment is that the first question is not which drug but which result, and that a treatment plan made before the molecular report is back may change. Two further decisions sit alongside: whether the primary tumour should be removed when it is causing no symptoms (NICE says consider it, and supplies a table of advantages and disadvantages to share), and when to take a break from oxaliplatin before the nerve damage becomes permanent. (FOLFOX (5-FU, leucovorin, oxaliplatin), FOLFIRI (5-FU, leucovorin, irinotecan), Cetuximab, Panitumumab, Bevacizumab, Encorafenib, PARADIGM, CRYSTAL & FIRE-3, BREAKWATER, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR), Sidedness (left vs right colon))
• Immunotherapy when the tumour is mismatch repair deficient: A small minority of bowel cancers that have spread have lost the mismatch repair machinery that proof-reads DNA, which leaves the tumour carrying very many mutations and makes it visible to the immune system. For those people, immunotherapy has replaced chemotherapy as the first treatment. NICE NG151 recommends nivolumab with ipilimumab as an option for untreated unresectable or metastatic colorectal cancer with high microsatellite instability or mismatch repair deficiency, and pembrolizumab as an option for untreated metastatic disease with the same markers, stopped after 2 years or earlier if the disease progresses; after fluoropyrimidine-based combination chemotherapy it recommends nivolumab with ipilimumab, and pembrolizumab only if that combination cannot be used. KEYNOTE-177 and CheckMate 8HW are the trials behind those recommendations and are on this record. The same biology is being tested before surgery, where a few weeks of immunotherapy has cleared the tumour in a large fraction of mismatch repair deficient colon cancers (NICHE-2) and of rectal cancers (the dostarlimab work and the registrational AZUR-1), but outside those trials NICE does not recommend it, so the question at the clinic is whether a trial is open. Everything therefore turns on the test: ask whether mismatch repair immunohistochemistry or microsatellite instability testing has been done and what the result was, because a mismatch repair deficient result also starts the Lynch syndrome pathway for your family. (Pembrolizumab, Nivolumab, Ipilimumab, KEYNOTE-177, CheckMate 8HW, NICHE-2, AZUR-1, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), MSI and mismatch-repair testing)
• Lynch syndrome testing, and what it means for your family: Around 3 in 100 UK bowel cancers are caused by Lynch syndrome, an inherited fault in one of the mismatch repair genes, and Bowel Cancer UK says testing should be offered to everyone at diagnosis because the result changes treatment as well as family risk. The route runs in order: the tumour is stained for the mismatch repair proteins (or tested for microsatellite instability); where MLH1 is lost, the laboratory checks for MLH1 promoter methylation, which usually means the loss is sporadic rather than inherited; and where the pattern still suggests an inherited cause, a germline blood test is offered through the genomics service. A positive result has three consequences. For you, immunotherapy becomes an option in advanced disease, and lifelong colonoscopy surveillance begins. For your relatives, each child, brother and sister has a one in two chance of carrying the same change, and Bowel Cancer UK says they should be offered the same test, which it calls cascade testing; it estimates that most of the 175,000 to 200,000 people in the UK with Lynch syndrome do not know. For prevention, NICE NG151 says to consider aspirin, taken daily and for a period of more than 2 years, to reduce the risk of colorectal cancer in people with Lynch syndrome, noting that in January 2020 this was an off-label use and that NICE has produced a patient decision aid to support the discussion. Bowel Cancer UK says surveillance means colonoscopy every 18 months to two years and can reduce the chance of dying from bowel cancer by as much as 72 percent. (Lynch syndrome, Germline (hereditary) testing, MSI and mismatch-repair testing, MLH1 promoter methylation (sporadic versus Lynch mismatch repair loss), Colonoscopy, Aspirin)
• A clinical trial or standard treatment: At several points in bowel cancer a trial is a reasonable choice beside standard treatment rather than a last resort, and NICE NG151 says so itself in two places: preoperative radiotherapy for early rectal cancer should only happen within a clinical trial, and people who defer surgery after a complete response should be encouraged to take part in a trial with data collected via a national registry. The open questions this record follows are the ones a trial would answer for you: whether circulating tumour DNA after surgery should decide who has chemotherapy and for how long; whether immunotherapy before surgery can replace an operation in mismatch repair deficient colon and rectal cancer; whether the newer RAS inhibitors help the large majority whose tumours are RAS-mutant; and how to make immunotherapy work in microsatellite-stable disease, where it so far does not. Bowel Cancer UK says some trials test new treatments and others test new ways of using existing treatments, and that if you would like to take part you should ask your healthcare team whether you are suitable for any current trials in your area; the NHS says you can ask your doctor or a patient organisation about trials you may be eligible to join, and that you can choose to leave at any point without giving a reason and without it affecting the care you receive. Practical points worth settling before you agree: how many extra visits, scans or biopsies are involved, whether travel is reimbursed, whether the trial is open at another hospital if not here, and what the standard alternative would be if you decline. (FOCUS4, AZUR-1, DYNAMIC, Multidisciplinary tumour boards)
• When to talk about palliative care: Palliative care is symptom control and support, and it is not a stage of the illness. Bowel Cancer UK says palliative care may start when you are diagnosed with advanced bowel cancer, or after treatment has stopped working, and that its aim is to improve quality of life; end of life care is a later part of the same service, usually in the last year of life. The NHS says that where bowel cancer cannot be cured you will be referred to a symptom control or palliative care team, who work with you to manage symptoms and help you and your loved ones get other support. A randomised trial in another cancer (Temel 2010) found that early palliative care alongside cancer treatment improved quality of life and mood, which is why the referral belongs alongside treatment rather than after it. In bowel cancer the concrete reasons are specific: pain from pelvic or liver disease, a bowel that is becoming obstructed, high stoma output and dehydration, poor appetite and weight loss, fatigue, low mood, sleep, and the practical questions about work, money and care at home. Bowel Cancer UK says you can choose where you would prefer to be cared for and where you wish to die, that care can be at home with the GP and community nurses, in a hospice (for a day or for a stay), in hospital or in a care home, and that your choices can be documented by your healthcare team and kept with your medical records so that the people close to you know them. Marie Curie sets out what palliative care covers and who provides it, and its support line and nurses are available to families as well as patients. (Early integrated palliative care, Palliative radiotherapy, Psycho-oncology and distress screening, Curative intent vs palliative intent)
• Rectal cancer: organ preservation and watch and wait: Consolidation chemotherapy after chemoradiotherapy, not induction before it, is the sequence that preserves the rectum: OPRA gave TME-free survival of 54 against 39 percent at five years (the long-term report, Journal of Clinical Oncology 2024; the first report gave 53 against 41 percent at three years), and CAO/ARO/AIO-12 found pathological complete response 25 against 17 percent with the same ordering. Patients with a clinical complete response on digital examination, endoscopy and MRI are offered watch and wait with endoscopy and MRI every three to four months. The International Watch & Wait Database (880 patients with a clinical complete response from 47 institutes) records two-year local regrowth of 25.2 percent, 88 percent of it within two years and 97 percent in the bowel wall where salvage surgery is possible, with five-year overall survival 85 percent and disease-specific survival 94 percent. In mismatch-repair deficient rectal cancer, dostarlimab for six months has produced complete clinical responses without surgery and AZUR-1 is the registrational trial. (OPRA, CAO/ARO/AIO-12, International Watch & Wait Database, AZUR-1, Dostarlimab, Clinical complete response (cCR), Organ preservation (watch-and-wait, bladder-sparing, larynx preservation))
• Metastatic disease, mismatch-repair deficient or MSI-high, first line: Immunotherapy, not chemotherapy: pembrolizumab (KEYNOTE-177) or nivolumab with ipilimumab (CheckMate 8HW). In England NICE TA709 recommends pembrolizumab stopped at two years and TA1065 recommends nivolumab with ipilimumab; TA914 places pembrolizumab after fluoropyrimidine therapy only where nivolumab with ipilimumab is unsuitable. The FDA approved nivolumab with ipilimumab for this indication on 8 April 2025. Universal mismatch-repair or MSI testing at diagnosis is what makes this route possible. (KEYNOTE-177, CheckMate 8HW, Pembrolizumab, Nivolumab, Ipilimumab, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer drugs in England: what NICE has recommended)
• Metastatic disease, RAS and BRAF wild-type, left-sided, first line: FOLFOX or FOLFIRI with panitumumab or cetuximab. PARADIGM showed panitumumab beats bevacizumab in left-sided RAS wild-type disease; FIRE-3 found overall survival 28.7 against 25.0 months for cetuximab against bevacizumab with FOLFIRI, while CALGB/SWOG 80405 found no overall difference (30.0 against 29.0 months) before sidedness was taken into account. Extended RAS testing of KRAS and NRAS exons 2, 3 and 4 is mandatory: PRIME showed patients with non-exon-2 RAS mutations do worse with panitumumab. In England TA439 funds cetuximab or panitumumab with FOLFOX or FOLFIRI first line only. (PARADIGM, CRYSTAL & FIRE-3, CALGB/SWOG 80405, PRIME, OPUS, Panitumumab, Cetuximab, FOLFOX (5-FU, leucovorin, oxaliplatin), FOLFIRI (5-FU, leucovorin, irinotecan), Sidedness (left vs right colon), Anti-EGFR antibody + chemotherapy in left-sided RAS/BRAF wild-type mCRC)
• Metastatic disease, RAS-mutant or right-sided, first line: FOLFOX, FOLFIRI or FOLFOXIRI with bevacizumab; EGFR antibodies are contraindicated. FOLFOXIRI plus bevacizumab gives a higher response rate and longer progression-free survival than a doublet (TRIBE: 12.1 against 9.7 months; TRIBE2 progression-free survival 2 of 19.2 against 16.4 months) at the cost of grade 3-4 neutropenia in about half, and is preferred where deep response matters. After six cycles, maintenance with a fluoropyrimidine and bevacizumab beats observation (CAIRO3: progression-free survival 2 of 11.7 against 8.5 months). In England bevacizumab is funded under TA1136 only when targeted treatment or immunotherapy is unsuitable. (TRIBE, TRIBE2, CAIRO3, AVF2107g, FOLFOXIRI (5-FU, leucovorin, oxaliplatin, irinotecan), Bevacizumab, Sidedness (left vs right colon))
• Metastatic disease, BRAF V600E: First line encorafenib with cetuximab and mFOLFOX6 (BREAKWATER), which the FDA approved on 20 December 2024 and converted to traditional approval on 24 February 2026. After previous treatment, encorafenib with cetuximab (BEACON CRC), which NICE recommends in England under TA668. The mechanism was established by SWOG S1406: BRAF blockade alone fails because it releases feedback activation of EGFR, so the EGFR antibody is not optional. There is no NICE recommendation for the first-line triplet. (BREAKWATER, BEACON CRC, SWOG S1406, Encorafenib, Cetuximab, FOLFOX (5-FU, leucovorin, oxaliplatin))
• Metastatic disease, KRAS G12C: Sotorasib with panitumumab (CodeBreaK 300, FDA approval 16 January 2025) or adagrasib with cetuximab (KRYSTAL-1 colorectal cohort, accelerated approval 21 June 2024) after fluoropyrimidine, oxaliplatin and irinotecan. The confirmatory trials are KRYSTAL-10 (NCT04793958, 461 patients, active but closed) and, for first-line use, CodeBreaK 301 (NCT06252649, 450 patients, recruiting). Neither combination has a NICE recommendation, so they are not routinely funded in England. (CodeBreaK 300, Phase 3 Study of MRTX849 With Cetuximab vs Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation (KRYSTAL-10), Study of Sotorasib, Panitumumab and FOLFIRI Versus FOLFIRI With or Without Bevacizumab-awwb in Treatment-naïve Participants With Metastatic Colorectal, Sotorasib, Adagrasib, Panitumumab, Cetuximab, KRAS & RAS inhibitors, KRAS G12C inhibitor + anti-EGFR antibody (colorectal))
• Metastatic disease, HER2-amplified and RAS wild-type: Tucatinib with trastuzumab (MOUNTAINEER, confirmed objective response 38.1 percent; FDA accelerated approval 19 January 2023) or trastuzumab deruxtecan at 5.4 mg/kg (DESTINY-CRC02, response 37.8 percent; DESTINY-CRC01 gave 45.3 percent at the higher 6.4 mg/kg dose with interstitial lung disease in 6 percent and two deaths). The tumour-agnostic HER2 IHC 3+ accelerated approval of trastuzumab deruxtecan came on 5 April 2024. MOUNTAINEER-03 (NCT05253651, 400 patients, primary completion December 2027) is testing first-line use. No NICE recommendation exists for either regimen in colorectal cancer. (MOUNTAINEER, MOUNTAINEER-03, DESTINY-CRC01, DESTINY-CRC02, Tucatinib, Trastuzumab, Trastuzumab deruxtecan)
• Metastatic disease, rarer biomarkers: NTRK, RET and POLE: NTRK fusions occur in well under 1 percent of colorectal cancers, almost always in right-sided, mismatch-repair deficient, RAS and BRAF wild-type tumours, and are treated with larotrectinib, which NICE recommends tumour-agnostically in England through the Cancer Drugs Fund only (TA630); entrectinib is no longer an option there, because TA644 has been withdrawn and its replacement TA1118 was terminated in January 2026. RET fusions are rarer still and are treated with selpercatinib under its tumour-agnostic approval. POLE or POLD1 exonuclease-domain mutations produce an ultramutated, immunotherapy-responsive tumour that is microsatellite-stable, so it is missed unless sequencing is done. All three are reasons to send comprehensive sequencing rather than a small hotspot panel in metastatic disease. (Larotrectinib, Entrectinib, Selpercatinib, Tumour-agnostic (tissue-agnostic) approval, Companion diagnostics)
• Microsatellite-stable disease and immunotherapy: Ninety-five percent of metastatic colorectal cancers are microsatellite-stable and do not respond to PD-1 blockade; IMblaze370 confirmed that adding a MEK inhibitor does not change this (overall survival 8.87 against 8.51 months with regorafenib, hazard ratio 1.00). The most promising current approach is Fc-enhanced CTLA-4 blockade: botensilimab with balstilimab gave an objective response rate of 17 percent (17 of 101 response-evaluable patients among 148 treated) with disease control in 61 percent and median progression-free survival 3.5 months in the phase 1 (Bullock, Nature Medicine 2024), and 21 percent with median overall survival 21.2 months in the 123 patients of the later cohort selected for the absence of liver metastases (Clinical Cancer Research 2026). Both are single-arm. Liver metastases deplete tumour-specific CD8 T cells, which is the reason for the restriction and the reason results in unselected populations have been so poor. (IMblaze370, A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer, Botensilimab, Balstilimab, Hot vs cold tumours, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Making microsatellite-stable colorectal cancer immunotherapy-responsive)
• Liver-limited and oligometastatic disease: Resection with curative intent where all disease can be removed with an adequate remnant; perioperative FOLFOX is the reference, although EORTC 40983 found the progression-free survival gain did not become a survival gain at 8.5 years (61.3 against 54.3 months, hazard ratio 0.88). Thermal ablation is the only local treatment with randomised survival evidence: CLOCC gave eight-year overall survival of 35.9 against 8.9 percent when radiofrequency ablation was added to systemic treatment. For initially unresectable liver metastases, CAIRO5 chose FOLFOXIRI with bevacizumab for right-sided or RAS/BRAF-mutant tumours and found panitumumab no better than bevacizumab for left-sided wild-type tumours, with resectability reviewed by a surgical panel every two months. Cetuximab must not be added around liver resection: New EPOC found median overall survival 55.4 against 81.0 months with it. (EORTC 40983, CLOCC, CAIRO5, New EPOC, Hepatectomy (liver resection), Thermal ablation (RFA, microwave, cryo), SBRT / SABR (stereotactic radiotherapy), Oligometastatic disease, Robotic & minimally invasive surgery)
• Peritoneal metastases: Complete cytoreductive surgery in selected patients with a Peritoneal Cancer Index of 25 or less gives a median overall survival above three years, but adding heated intraperitoneal oxaliplatin does not: PRODIGE 7 found 41.7 against 41.2 months with more late grade 3 or worse complications. HIPEC also failed as prophylaxis in T4 or perforated colon cancer (COLOPEC) and as systematic second-look surgery (PROPHYLOCHIP). Selection for surgery, and systemic chemotherapy, are what change the outcome; other agents and delivery methods, including pressurised intraperitoneal aerosol chemotherapy, remain investigational. (PRODIGE 7, COLOPEC, PROPHYLOCHIP-PRODIGE 15, HIPEC / PIPAC (intraperitoneal chemotherapy), Debulking (cytoreductive surgery), Colorectal cancer: the failed and stopped programmes, and why)
• The failed and stopped programmes: Adjuvant cetuximab (N0147, PETACC-8) gave no benefit and more toxicity; cetuximab around liver resection shortened life (New EPOC, 55.4 against 81.0 months). Oxaliplatin HIPEC failed three times (PRODIGE 7, COLOPEC, PROPHYLOCHIP). Checkpoint inhibition with a MEK inhibitor failed in microsatellite-stable disease (IMblaze370, hazard ratio 1.00 against regorafenib). Treating molecular recurrence with late-line chemotherapy failed (ALTAIR). In access, NICE did not recommend ziv-aflibercept (TA307) despite a positive phase 3 trial. (Colorectal cancer: the failed and stopped programmes, and why, Alliance N0147, PETACC-8, New EPOC, PRODIGE 7, COLOPEC, PROPHYLOCHIP-PRODIGE 15, IMblaze370, ALTAIR)
• UK access to treatments (NICE, September 2026): Funded in England: cetuximab and panitumumab first line in RAS wild-type disease (TA439); pembrolizumab first line for MSI-high or dMMR disease (TA709) and after chemotherapy where nivolumab with ipilimumab is unsuitable (TA914); nivolumab with ipilimumab first line (TA1065) and after previous treatment (TA716); encorafenib with cetuximab after previous treatment in BRAF V600E disease (TA668); trifluridine-tipiracil (TA405) and with bevacizumab after two lines (TA1008); regorafenib (TA866); fruquintinib at third line or later where trifluridine-tipiracil with bevacizumab is unsuitable (TA1079); bevacizumab with fluoropyrimidine chemotherapy first and second line where targeted treatment or immunotherapy is unsuitable (TA1136); larotrectinib for NTRK fusions, through the Cancer Drugs Fund rather than routine commissioning (TA630). Withdrawn: entrectinib (TA644, replaced by the terminated TA1118). Not funded: ziv-aflibercept (TA307, not recommended), and, for want of any appraisal, tucatinib with trastuzumab, trastuzumab deruxtecan in colorectal cancer, sotorasib with panitumumab, adagrasib with cetuximab and first-line encorafenib with chemotherapy. The clinical guideline is NG151. (Colorectal cancer drugs in England: what NICE has recommended, Cancer Drugs Fund (England))
• Palliation: obstruction, stents and stomas: A self-expanding metal stent at colonoscopy relieves a left-sided obstruction within a day or two, either as a bridge to elective resection without a stoma or as definitive palliation; perforation, migration and re-obstruction are the risks and stenting is avoided during bevacizumab treatment. A defunctioning or end colostomy is preferred for right-sided or multi-level obstruction, peritoneal disease and a longer prognosis; right-sided obstruction is usually resected with primary anastomosis. Inoperable malignant bowel obstruction is managed medically with a syringe driver: an anti-emetic, hyoscine butylbromide or octreotide, dexamethasone and opioid analgesia, with a venting gastrostomy if vomiting persists. (Palliation in colorectal cancer: obstruction, stents, stomas and liver capsule pain, Stoma (colostomy, ileostomy, urostomy), Endoscopic resection (EMR / ESD), Early integrated palliative care)
• Acute left-sided large bowel obstruction: Stenting for people being treated with palliative intent; either stenting or emergency surgery when potentially curative treatment is suitable. In CReST, stenting as a bridge to elective surgery relieved obstruction in 82.4 percent and cut stoma formation from 67.9 to 47.5 percent in patients treated with curative intent, with no difference in 30-day mortality, hospital stay, 3-year recurrence or survival. (Obstruction and T4 disease in bowel cancer, Endoscopy (EGD, EUS, ERCP), Colectomy)
• Referral when symptoms suggest bowel cancer: Offer a quantitative faecal immunochemical test to the symptom groups NICE lists and refer on the suspected cancer pathway at 10 micrograms of haemoglobin per gram of faeces or above; refer a rectal mass without testing first; safety net people who do not return a sample or test below the threshold, and do not let a low result delay referral where clinical concern is strong. (Faecal immunochemical test (FIT), NHS bowel cancer screening programme, Emergency presentation (route to diagnosis))
• Later lines, when chemotherapy stops working: When the cancer grows through the first and second lines, there is still a recognised sequence, and knowing it in advance makes each step less sudden. NICE NG151 points to its appraisals for metastatic colorectal cancer previously treated with fluoropyrimidine-based chemotherapy, anti-VEGF or anti-EGFR therapy: trifluridine with tipiracil plus bevacizumab after 2 systemic treatments (the SUNLIGHT combination), fruquintinib after 2 systemic treatments if trifluridine with tipiracil plus bevacizumab is not suitable (FRESCO-2), regorafenib, and trifluridine with tipiracil alone. It also lists what is not recommended at this point, including aflibercept with irinotecan and fluorouracil after oxaliplatin, and cetuximab or panitumumab monotherapy after first-line chemotherapy. Where a rarer change is present the sequence changes: encorafenib with cetuximab for BRAF V600E after previous systemic treatment, larotrectinib through the Cancer Drugs Fund for NTRK fusion-positive tumours when there are no other satisfactory options, and the HER2 and KRAS G12C options on this record's other rows. These drugs are given to hold the cancer and protect quality of life rather than to cure, so the honest questions are what each is likely to buy, what it costs in side effects and hospital visits, how progression will be recognised, and what the stopping rule is. Bowel Cancer UK has pages on treating advanced bowel cancer and on taking a break from treatment; both are legitimate choices, and so is a trial. (Trifluridine/tipiracil, Bevacizumab, Fruquintinib, Regorafenib, SUNLIGHT, FRESCO-2)
• Metastatic disease, later lines: Trifluridine-tipiracil with bevacizumab (SUNLIGHT: overall survival 10.8 against 7.5 months; FDA approval 2 August 2023; NICE TA1008), then fruquintinib (FRESCO-2: 7.4 against 4.8 months; FDA approval 8 November 2023; NICE TA1079 only where trifluridine-tipiracil with bevacizumab is unsuitable) or regorafenib (CORRECT: 6.4 against 5.0 months; NICE TA866). Second-line anti-angiogenic options after an oxaliplatin regimen are ziv-aflibercept (VELOUR: 13.50 against 12.06 months, not recommended by NICE in TA307) and ramucirumab (RAISE: 13.3 against 11.7 months, no NICE recommendation). Anti-EGFR rechallenge guided by circulating tumour DNA is promising and unproven in phase 3. (SUNLIGHT, FRESCO-2, CORRECT, CONCUR, RECOURSE, FRESCO, VELOUR, RAISE, Trifluridine/tipiracil, Fruquintinib, Regorafenib, Ziv-aflibercept, Ramucirumab)
• Anti-EGFR resistance and rechallenge: Resistance to EGFR antibodies is universal and arises through RAS, BRAF and EGFR ectodomain mutant clones that expand under treatment and decay once it stops, which is why rechallenge is worth trying and why it must be selected by a blood test rather than by time alone. CHRONOS screened 52 patients with circulating tumour DNA, excluded the 31 percent with a resistance mutation and rechallenged the rest with panitumumab alone: 30 percent responded and 63 percent had disease control. CAVE rechallenged with cetuximab and avelumab and found median overall survival 17.3 months where baseline plasma RAS and BRAF were wild-type against 10.4 months where they were mutated (hazard ratio 0.49). Both trials are single-arm, so rechallenge is an option to consider in a trial or after discussion, not a standard. (CHRONOS, CAVE mCRC, Panitumumab, Cetuximab, Liquid biopsy (ctDNA), Circulating tumour DNA (ctDNA))

From the standard of care recorded for this cancer; which apply depends on your stage and biomarkers. Ask which the team recommends and why.