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Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year.
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668 trials on record are attached to one of the types below rather than to Colorectal cancer itself. They are grouped by the type that holds them, so someone still working out which type they have can see the whole field from here.
The 48 most recent of 135 papers; see them all →
For someone offered the test, these are the numbers that describe what a result means in an NHS population: about 1 in 100 tests came back positive each year, between 46 and 58 in 100 positives were cancer, and a negative result left about 1 in 100 with an undetected cancer within the year. The test found between a quarter and a third of all cancers diagnosed in a screening round, and about half to two thirds of the 12 cancer types it was designed to find. Whether finding them this way reduces late-stage diagnoses is the primary question, and this paper says only that the answer was no; the primary-endpoint paper had not appeared on Europe PMC by 23 September 2026.
Patients with newly diagnosed metastatic colorectal cancer whose tumour carries a BRAF V600E mutation, which is about 8-12% of cases, should now be offered encorafenib and cetuximab together with FOLFOX from the start rather than after chemotherapy fails; median survival has roughly doubled to about two and a half years. BRAF testing at diagnosis is therefore essential, alongside RAS and mismatch repair testing. The regimen is more toxic than chemotherapy alone.
For colon cancer survivors, a prescribed, supported exercise programme is now an evidence-based treatment with a survival benefit comparable to many drugs. Health systems will need to fund exercise consultants as they fund chemotherapy. The trial does not tell us whether unsupervised advice achieves the same.
This is the validation study behind the July 2026 FDA approval of SimpleScreen CRC. For someone who will not take a stool test or colonoscopy it offers a real option for catching cancer, but because it misses most advanced polyps it prevents fewer cancers than the established tests, and a positive result still needs a colonoscopy.
If a childhood exposure to colibactin-producing Escherichia coli writes APC mutations into the colon decades before a tumour appears, then the rise in early-onset bowel cancer may be preventable by something done in childhood rather than by screening alone.
For mismatch repair-deficient rectal cancer, six months of a single antibody now replaces chemotherapy, radiotherapy and an operation, and the same appears to be true for early-stage mismatch repair-deficient cancers of other organs.
The first credible response signal in microsatellite stable colorectal cancer, and the reason the field's attention has moved to Fc engineering and to excluding patients with active liver metastases, in whom responses are rare.
This is the number behind almost every statement about how much cancer there is. It shows the burden shifting towards low- and middle-income countries and towards older populations, which is why prevention, screening and affordable treatment in those settings decide the global trend. OnCo's country and prevalence pages draw on the same GLOBOCAN release.
Query for this cancer: (TITLE:"Colorectal cancer" OR ABSTRACT:"Colorectal cancer" OR TITLE:"COAD" OR ABSTRACT:"COAD" OR TITLE:"COADREAD" OR ABSTRACT:"COADREAD" OR TITLE:"TCGA-COAD" OR ABSTRACT:"TCGA-COAD" OR TITLE:"TCGA-COADREAD" OR ABSTRACT:"TCGA-COADREAD" OR TITLE:"colorectal adenocarcinoma TCGA COAD and READ cohorts" OR ABSTRACT:"colorectal adenocarcinoma TCGA COAD and READ cohorts") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Colorectal cancer, not a curated reading list.
Heidelberger; still the backbone of colorectal chemotherapy 70 years later.
Heald found cancer deposits in the mesorectum several centimetres below the tumour and removed the whole envelope instead of cutting through it; the first 50 curative operations had no pelvic or staple-line recurrence at two years.
Quirke sliced 52 rectal specimens transversely: 14 had tumour at the lateral margin and 12 of those recurred locally, which redefined recurrence as a problem of surgery and pathology rather than of biology alone.
Four alterations measured across 172 specimens accumulate in step with progression: ras in 58% of adenomas over 1 cm, 18q loss in 73% of carcinomas, 17p loss almost only in carcinomas.
Fluorouracil with levamisole improved survival after resection of node-positive colon cancer (1990); MSH2 and MLH1 were cloned in 1993. MOSAIC added oxaliplatin in 2004.
Nottingham (1996, 152,850 people, 15 percent reduction) and Funen (1996, 18 percent) follow the Minnesota result and build the case for national programmes.
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.
TGFBR2, the growth brake, is destroyed by slippage in a short repeat in mismatch repair deficient colon cancer lines.
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.
1,168 patients; five-year local recurrence 11 versus 27 percent and overall survival 58 versus 48 percent, against surgery that was not standardised.
MLH1 promoter hypermethylation explains most sporadic microsatellite-unstable cancers and is reversible in the laboratory.
FOLFIRI and FOLFOX double median metastatic survival from ~12 to ~20 months.
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.
Verwaal, 105 patients: median survival 22.3 versus 12.6 months, at 8 percent treatment-related mortality.
First anti-angiogenic and first anti-EGFR antibodies; MOSAIC establishes adjuvant FOLFOX.
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.
3,239 patients, 91 percent node-negative: relative risk of death 0.82, an absolute survival gain of about 3.6 percent.
Cetuximab improved survival only in K-ras wild-type tumours (9.5 against 4.8 months) and did nothing in mutant ones, creating the first negative predictive biomarker in solid tumours.
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.
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.
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.
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.
National Polyp Study at 23 years: colorectal cancer mortality halved against the general population.
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.
RECOURSE established the oral combination after fluoropyrimidine, oxaliplatin, irinotecan and the antibodies had run out.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Organ preservation without surgery in the first Memorial Sloan Kettering cohort (Cercek, NEJM); panitumumab beat bevacizumab in left-sided RAS wild-type disease.
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.
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.
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.
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.
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.
CIRCULATE-US (NRG-GI008, 1,912 estimated participants) has a primary completion date of 10 March 2029 and the French CIRCULATE (1,980 estimated) of March 2032; NordICC's study completion, and the 15-year screening mortality answer, is listed for July 2036.