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Every dated change on the records linked to Colorectal cancer, newest first: approvals and regulatory steps on its medicines, trials that reported, guideline versions, milestones, and when this page itself was checked. Dates come from the records; none is inferred. Orientation, not medical advice.
First- and second-line metastatic colorectal cancer with fluoropyrimidine-based chemotherapy, only when targeted treatment or immunotherapy is unsuitable
First-line BRAF V600E mCRC with cetuximab and chemotherapy
Metastatic colorectal cancer with a BRAF V600E mutation
Colorectal cancer screening in average-risk adults aged 45 and older
Median disease-free survival 9.
Primary endpoint (sustained cCR at 12 months) met; rates pending congress presentation.
Second-line daraxonrasib 300 mg in 26 patients with RAS G12-mutated pancreatic cancer: objective response 35 percent, median progression-free survival 8.
A milestone in how this cancer is treated.
The American Cancer Society reports colorectal cancer incidence rising 3 percent a year in adults aged 20 to 49 and 0.4 percent a year at 50 to 64, while falling 2.5 percent a year in the over-65s; rectal cancer is now 32 percent of cases, up from 27 percent in the mid-2000s.
Metastatic colorectal cancer at third line or later, only when trifluridine-tipiracil with bevacizumab is unsuitable
Untreated unresectable or metastatic MSI-high or dMMR colorectal cancer, with nivolumab
Untreated unresectable or metastatic MSI-high or dMMR colorectal cancer, with ipilimumab
Unresectable or metastatic MSI-high or dMMR colorectal cancer, with ipilimumab
KRAS G12C mCRC with sotorasib
KRAS G12C colorectal cancer with panitumumab
KRAS G12C-mutated metastatic colorectal cancer after fluoropyrimidine, oxaliplatin and irinotecan chemotherapy, with panitumumab
3-year recurrence HR 0.
3-year DFS 86.
OS 30.
DFS HR 0.
ctDNA is strongly prognostic (three-year recurrence-free survival 87 against 49 percent) but de-escalation was not non-inferior and escalation did not help.
Sensitivity 79.
A milestone in how this cancer is treated.
KRAS G12C colorectal cancer with cetuximab
KRAS G12C-mutated locally advanced or metastatic colorectal cancer after fluoropyrimidine, oxaliplatin and irinotecan chemotherapy, with cetuximab
KRAS G12C mCRC with adagrasib
Colorectal cancer screening in average-risk adults aged 45 and older
Metastatic colorectal cancer with a BRAF V600E mutation, with cetuximab and mFOLFOX6, previously untreated
Previously treated metastatic colorectal cancer
Colorectal cancer screening, average-risk adults ≥45
Unresectable or metastatic HER2-positive (IHC 3+) solid tumours after previous systemic treatment, including colorectal cancer
Metastatic colorectal cancer after two lines of treatment, with bevacizumab
Sensitivity 93.
First-line PFS 54.
Sensitivity 83.
Placebo-adjusted weight gain 2.
A milestone in how this cancer is treated.
An Fc-enhanced CTLA-4 antibody with a PD-1 antibody gave 17% responses and 61% disease control in 101 evaluable heavily pre-treated microsatellite-stable patients.
Refractory mCRC with trifluridine/tipiracil (SUNLIGHT)
Refractory mCRC after fluoropyrimidine, oxaliplatin, irinotecan, anti-VEGF, and anti-EGFR if appropriate
Previously treated MSI-high or dMMR endometrial, biliary, colorectal, gastric or small intestine cancer
Mismatch repair deficient or MSI-high tumours: NICE TA914 (20 September 2023) covers previously treated endometrial, gastric, small intestine, biliary and colorectal cancer and does not include pancreatic cancer
Metastatic colorectal cancer after previous treatment or when those treatments are unsuitable
Companion diagnostic for cetuximab and panitumumab (KRAS/NRAS wild-type colorectal cancer) with tumour-profiling claims
Refractory mCRC with bevacizumab
HER2+ RAS-wild-type mCRC with trastuzumab
HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer that has progressed after fluoropyrimidine, oxaliplatin and irinotecan, with trastuzumab
FOLFOXIRI plus bevacizumab better than a doublet for right-sided or RAS/BRAF-mutant disease; panitumumab no better than bevacizumab for left-sided wild-type disease.
GALAXY: ctDNA+ post-op HR for recurrence ~10; ALTAIR: DFS endpoint not met.
PFS HR 0.
ORR 37.
Residual or recurrent disease within two years 16.
OS 7.
Pancreatic cancer cohort: objective response in 7 of 21 patients (33.
Fewer severe complications and faster recovery with prehabilitation; surgery not delayed.
5-year disease-free survival 80.
OS 10.
Six weeks of oxaliplatin and fluoropyrimidine before surgery, then 18 weeks after, left fewer patients with residual or recurrent disease at two years than 24 weeks after surgery alone; NICE NG151 now says to consider preoperative therapy for cT4 colon cancer.
A milestone in how this cancer is treated.
Objective response 30 percent (8 of 27) and disease control 63 percent in ctDNA-selected patients; 31 percent of those screened were excluded by a resistance mutation.
Chemotherapy use 15% vs 28% with non-inferior RFS.
Phase 2 ORR 38.
pCR 68%, major pathologic response 95%; 3-year DFS 100%.
10-year colorectal cancer risk 0.
3-year disease-free survival 76% in both arms; 3-year survival without total mesorectal excision 41% (induction) vs 53% (consolidation).
OS 37.
Three-year disease-free survival 64.
DYNAMIC cut adjuvant chemotherapy use in resected stage II colon cancer from 28% to 15% with non-inferior two-year recurrence-free survival, the first randomised de-escalation on a ctDNA result in any solid tumour.
Organ preservation without surgery in the first Memorial Sloan Kettering cohort (Cercek, NEJM); panitumumab beat bevacizumab in left-sided RAS wild-type disease.
84,585 people in Poland, Norway and Sweden; a single invitation cut the 10-year risk of colorectal cancer from 1.20 to 0.98 percent, with 455 invitations needed to prevent one cancer, in a trial where only 42 percent of those invited attended.
BRAF V600E mutation-positive metastatic colorectal cancer after previous systemic treatment, with cetuximab
Untreated metastatic colorectal cancer with high microsatellite instability or mismatch repair deficiency
Median overall survival 11.
Confirmed objective response 45.
FOCUS4-C: adavosertib improved progression-free survival in RAS and TP53 co-mutated tumours (hazard ratio 0.
3-year disease-free survival 76% vs 69% (hazard ratio 0.
Median overall survival 41.
Progression-free survival hazard ratio 0.
Relapse-free survival hazard ratio 1.
Confirmed objective response 30 percent in tissue-positive and 28 percent in ctDNA-positive patients, against 0 percent in a matched real-world reference group.
Adding oxaliplatin hyperthermic intraperitoneal chemotherapy to complete cytoreductive surgery changed nothing (median overall survival 41.7 against 41.2 months in 265 patients) and caused more late complications; in the same year the US task force lowered the screening start age to 45.
RAPIDO cuts three-year treatment failure from 30.4 to 23.7 percent; PRODIGE 23 raises three-year disease-free survival from 69 to 76 percent.
BRAF V600E mCRC with encorafenib
BRAF V600E mCRC with cetuximab, previously treated
NTRK fusion-positive solid tumours, including colorectal cancer
NTRK fusion-positive solid tumours, including colorectal cancer
therascreen BRAF V600E: encorafenib plus cetuximab in colorectal cancer
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
PFS 16.
Median overall survival 55.
Three-year disease-free survival 44 percent with second-look surgery and HIPEC against 53 percent with surveillance.
3-year disease-related treatment failure 23.
Continuous cohort reporting: positive signals for pembrolizumab in high tumour mutational burden cancers and trastuzumab plus pertuzumab in ERBB2-amplified colorectal cancer; palbociclib in CDKN2A-altered lung cancer and several other matches were negative.
Progression-free survival 2 of 19.
A milestone in how this cancer is treated.
One guideline for colorectal cancer from Lynch syndrome prevention to follow-up, alongside the BSG, ACPGBI and Public Health England rules that decide who gets a surveillance colonoscopy and when.
Median overall survival 9.
Pathological complete response 25 percent with consolidation chemotherapy against 17 percent with induction.
Peritoneal metastasis-free survival at 18 months 80.
Median overall survival 8.
5-year OS 42.
665 patients; encorafenib with cetuximab and binimetinib 9.0 versus 5.4 months, the doublet 8.4 months.
From June 2019 every screening invitation in England carries a faecal immunochemical test kit, read at a threshold of 120 micrograms of haemoglobin per gram of faeces; the programme now invites everyone aged 50 to 74 every two years.
About 1% of morphologically normal colorectal crypts in middle age carry a probable driver mutation, so adenomas and cancers are the rare outcomes of a process happening everywhere.
BRAF V600E-mutant metastatic colorectal cancer, with cetuximab
Refractory mCRC (FRESCO)
dMMR nivolumab plus ipilimumab cohort: objective response 55 percent, twelve-month overall survival 85 percent.
Median overall survival 9.
Three months non-inferior to six for CAPOX and for low-risk (T1-3 N1) disease; six months better for T4 or N2.
Two-year local regrowth 25.
Response in 23 percent of the first 230 patients; trastuzumab plus pertuzumab gave a 32 percent response rate in HER2-amplified colorectal cancer, now a guideline option; atezolizumab activity rose with tumour mutational burden.
Three-year disease-free survival 76.
A milestone in how this cancer is treated.
Among people with a complete clinical response after chemoradiotherapy who kept their rectum, local regrowth reached 25.2 percent at two years, almost all in the bowel wall and nearly all within two years; five-year overall survival was 85 percent.
Mice with all four main colorectal mutations reproduce human microsatellite-stable disease and answer checkpoint blockade only once TGF-beta is inhibited; across 1,211 tumours, WNT activation tracks the absence of T cells and MSI-high tumours have often deleted B2M and HLA.
Previously untreated EGFR-expressing RAS wild-type metastatic colorectal cancer with FOLFOX or FOLFIRI
Previously untreated RAS wild-type metastatic colorectal cancer with FOLFOX or FOLFIRI
Median overall survival 30.
Eight-year overall survival 35.
Delaying surgery after 5 x 5 Gy is non-inferior for local recurrence and has fewer postoperative complications.
The UK Flexible Sigmoidoscopy Screening Trial, 170,034 people, reported a 26 percent lower incidence and a 30 percent lower mortality in those invited, and 35 and 41 percent lower in those who attended.
Based on KEYNOTE-016/164 and others; dMMR CRC becomes the model immunotherapy-responsive GI tumour.
Across six randomised trials, EGFR antibodies helped left-sided RAS wild-type tumours (hazard ratio 0.75) and not right-sided ones (1.12); non-V600 BRAF mutations, 22% of all BRAF mutations, carry median survival of 60.7 months against 11.4. Universal molecular testing is codified in guideline form.
Previously treated metastatic colorectal cancer
Metastatic colorectal cancer after available therapies
Trastuzumab plus lapatinib produced objective responses in roughly a third of refractory HER2-amplified colorectal cancers.
Circulating tumour DNA after resection of stage II colon cancer gave a recurrence hazard ratio of 18 in 230 patients, the measurement every later trial of residual disease is built on.
HERACLES treated RAS wild-type patients with HER2 amplification using trastuzumab and lapatinib and got responses in 8 of 27.
Refractory metastatic colorectal cancer
Progression-free survival 2 of 11.
Median overall survival 8.
Median overall survival 13.
Median overall survival 7.
The consensus molecular subtypes reconcile six classifications across 4,151 samples; two papers published together show the mesenchymal signal comes from fibroblasts rather than cancer cells. The HER2 scoring criteria for colorectal cancer are validated the same year.
Four of 10 deficient colorectal cancers responded to pembrolizumab and none of 18 proficient ones, with a mean of 1,782 against 73 mutations per tumour.
RECOURSE established the oral combination after fluoropyrimidine, oxaliplatin, irinotecan and the antibodies had run out.
Colorectal cancer screening in average-risk adults aged 50 and older (later 45 and older)
First-line RAS wild-type mCRC with FOLFOX
Not recommended
Sensitivity 92.
No disease-free survival benefit from cetuximab in KRAS wild-type disease (hazard ratio 1.
Progression-free survival 12.
Metastatic colorectal cancer after available therapies
Metastatic colorectal cancer resistant to or progressing after oxaliplatin, with FOLFIRI
Metastatic colorectal cancer resistant to or progressing after an oxaliplatin-containing regimen, with FOLFIRI
Median overall survival 6.
No overall survival difference at 8.
In RAS wild-type disease, overall survival 26.
A further 17% of KRAS exon 2 wild-type patients in PRIME carry another RAS mutation and gain nothing from panitumumab, which moved the label to all RAS; germline POLE and POLD1 proofreading variants are identified as a new predisposition syndrome.
CORRECT: regorafenib gave 6.4 against 5.0 months after everything else had been used, the first drug approved for that setting.
Metastatic colorectal cancer, previously treated
Metastatic colorectal cancer after fluoropyrimidine, oxaliplatin, irinotecan, anti-VEGF and, if RAS wild-type, anti-EGFR therapy
therascreen KRAS: cetuximab and panitumumab eligibility in metastatic colorectal cancer
Metastatic colorectal cancer resistant to or progressing after oxaliplatin, with FOLFIRI
Metastatic colorectal cancer resistant to or progressing after an oxaliplatin-containing regimen, with FOLFIRI
Three-year disease-free survival 71.
Standardised incidence-based mortality ratio 0.
Median overall survival 13.
National Polyp Study at 23 years: colorectal cancer mortality halved against the general population.
KRAS-mutant clones emerge in plasma 5 to 6 months into panitumumab and are detectable up to 10 months before progression; modelling places them in the tumour before treatment.
TCGA read 276 tumours on every platform, found 16% hypermutated and added ARID1A, SOX9 and FAM123B to the driver list; the same year, R-spondin fusions were found in 10% of colon tumours, mutually exclusive with APC mutation.
Advanced gastric cancer with cisplatin; metastatic colorectal cancer intolerant of other fluoropyrimidines added 2022 (Teysuno)
No overall survival gain from adding cetuximab to oxaliplatin-based first-line chemotherapy, including in KRAS wild-type disease.
In KRAS wild-type disease, progression-free survival hazard ratio 0.
Colorectal cancer incidence 23 percent lower and mortality 31 percent lower in those invited to a single flexible sigmoidoscopy (33 percent and 43 percent among attenders); the 17-year follow-up confirmed the effect lasted.
Atkin, 170,432 people: incidence down 23 percent and mortality 31 percent, still holding at 17 years. Kaminski: endoscopists finding adenomas in under 20 percent of people leave a roughly tenfold higher interval cancer risk.
Sessile serrated lesions and traditional serrated adenomas, with promoter methylation and BRAF or KRAS mutation, account for about 30 percent of colorectal carcinomas and for most sporadic mismatch repair-deficient tumours.
CRYSTAL KRAS-WT OS 23.
Local recurrence at three years 4.
Five-year disease-free survival 56.
Loss of the 3' exons of EPCAM silences the neighbouring MSH2 gene by transcriptional read-through, in EpCAM-expressing tissue only.
1,350 patients; local recurrence 61 percent lower with short-course radiotherapy before surgery than with selective postoperative chemoradiotherapy, with no survival difference.
Metastatic colorectal cancer; RAS wild-type from 2013
Overall survival hazard ratio 0.
Relative risk of death 0.
3,239 patients, 91 percent node-negative: relative risk of death 0.82, an absolute survival gain of about 3.6 percent.
EGFR-expressing mCRC after chemotherapy (later RAS wild-type)
Magnetic resonance imaging predicted a clear circumferential resection margin correctly in 327 of 349 patients (94 percent), with 92 percent specificity, reproducibly across 11 units.
195 methylation markers across 295 tumours: CIMP-positive tumours are a distinct subset encompassing almost all BRAF-mutant cancers (odds ratio 203), and are where sporadic MLH1 silencing comes from.
In 408 patients across 11 European units, high-resolution pelvic magnetic resonance imaging predicted a clear circumferential margin with 92 percent specificity, and the scan started deciding who needs treatment before surgery.
First-line metastatic colorectal cancer with 5-FU chemotherapy
EGFR-expressing metastatic colorectal cancer; later restricted to RAS wild-type
EGFR-expressing metastatic colorectal cancer (later restricted to RAS wild-type)
Median overall survival 20.
5-year local recurrence 6% (preoperative) vs 13% (postoperative); overall survival unchanged.
Three-year disease-free survival 78.
First anti-angiogenic and first anti-EGFR antibodies; MOSAIC establishes adjuvant FOLFOX.
Median survival 22.
Verwaal, 105 patients: median survival 22.3 versus 12.6 months, at 8 percent treatment-related mortality.
Colorectal, gastric and breast cancer
Local recurrence at two years 2.
1,861 patients; two-year local recurrence 2.4 versus 8.2 percent with preoperative radiotherapy, two-year survival identical at 82.0 versus 81.8 percent.
Metastatic breast cancer after anthracycline and taxane; later adjuvant and metastatic colorectal cancer, rectal chemoradiotherapy
MLH1 promoter hypermethylation explains most sporadic microsatellite-unstable cancers and is reversible in the laboratory.
Five-year local recurrence 11 against 27 percent, with better overall survival.
1,168 patients; five-year local recurrence 11 versus 27 percent and overall survival 58 versus 48 percent, against surgery that was not standardised.
Microsatellite-stable colorectal cancers gain or lose chromosomes above 10^-2 per chromosome per division, a dominant and continuing defect distinct from mismatch repair failure.
Metastatic colorectal cancer after 5-FU; first line with 5-FU/LV 2000
Metastatic colorectal cancer
Colorectal cancer mortality ratio 0.
Colorectal cancer deaths 360 in the screened group against 420 in the control group, a 15 percent reduction in cumulative mortality (odds ratio 0.
Thirteen-year colorectal cancer mortality 5.
The National Polyp Study found 76 to 90 percent fewer cancers than expected in 1,418 patients whose adenomas were removed; in the same year the Minnesota trial showed annual faecal occult blood testing cut 13-year colorectal cancer mortality by 33 percent in 46,551 people.
Nottingham (1996, 152,850 people, 15 percent reduction) and Funen (1996, 18 percent) follow the Minnesota result and build the case for national programmes.