# Sidedness (left vs right colon)

Source: https://onco.cc/terms/sidedness/  
OnCo record `sidedness` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Where in the colon a tumour starts changes its biology and which drugs work. Left-sided tumours respond to EGFR antibodies; right-sided ones do not.

## Summary

Right-sided (caecum to transverse) tumours are more often dMMR, BRAF-mutant, mucinous, and worse prognosis; left-sided (splenic flexure to rectum) are more often chromosomally unstable and EGFR-dependent. CALGB 80405, FIRE-3, and PARADIGM showed anti-EGFR benefit is confined to left-sided RAS wild-type disease. Embryologic origin (midgut vs hindgut) underlies the difference.

## Fields

- Kind: Term
- Last checked: 2026-09-07

## Notes

- Measured, not asserted: in 7,237 MSK-IMPACT samples with a named subsite, microsatellite instability was 24.3% on the right against 5.2% on the left, BRAF V600E 19.2% against 2.9%, KRAS 51.9% against 39.7%, PIK3CA 32.4% against 15.5%, APC 65.0% against 77.6% and TP53 56.7% against 79.2% (cBioPortal crc_msk_2026). The predictive effect is the reason it matters: across six randomised trials in 2,159 RAS wild-type patients, adding an EGFR antibody improved overall survival on the left (hazard ratio 0.75) and not on the right (1.12), interaction p less than 0.001 (Arnold 2017), with the same interaction inside CRYSTAL and FIRE-3 separately (Tejpar 2017). The mechanism is that right-sided microsatellite-stable tumours carry mitogenic pathway mutations while left-sided ones are ligand dependent (Yaeger 2018, Missiaglia 2014). The caution is that the bowel is a gradient, not two halves: RAS mutation falls from 70% at the caecum to 43% at the hepatic flexure and the transverse colon clusters with the left (Loree 2018).
- The pooled numbers. Individual patient data from six randomised trials (CRYSTAL, FIRE-3, CALGB 80405, PRIME, PEAK and 20050181) covering 2,159 people with RAS wild-type unresectable disease, 515 right-sided and 1,644 left-sided, showed a worse prognosis for right-sided tumours in both control and experimental arms (overall survival hazard ratios 2.03 and 1.38; progression-free survival 1.59 and 1.25). Adding an EGFR antibody to chemotherapy helped left-sided tumours (overall survival hazard ratio 0.75, progression-free survival 0.78) and did not help right-sided ones (1.12 for both), with a significant interaction (Arnold 2017). The analysis is retrospective and covers 37.5 percent of the patients randomised in those trials.
- Side is recorded on every metastatic case alongside RAS and BRAF status before first-line treatment is chosen (NICE NG151 1.4.1). In the UK the rectum is the commonest single site of bowel cancer (Cancer Research UK, 2016 to 2018).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Colorectal_cancer
- ClinicalTrials.gov NCT02394795: PARADIGM: https://clinicaltrials.gov/study/NCT02394795
- Arnold, Ann Oncol 2017: prognostic and predictive value of primary tumour side in RAS wild-type metastatic colorectal cancer, pooled analysis of six randomised trials (2,159 patients): https://doi.org/10.1093/annonc/mdx175
- NICE NG151: colorectal cancer, recommendations (Lynch 1.1, local disease 1.3, biomarkers 1.4, metastatic disease 1.5, ongoing care and support including follow-up 1.6): https://www.nice.org.uk/guidance/ng151/chapter/Recommendations
- CRUK: bowel cancer incidence statistics: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bowel-cancer/incidence

## Connected records

- cancers: [BRAF V600E-mutant colorectal cancer](https://onco.cc/cancers/braf-v600e-colorectal/), [Colon cancer (adenocarcinoma of the colon)](https://onco.cc/cancers/colon-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Early-onset colorectal cancer (under 50)](https://onco.cc/cancers/early-onset-colorectal/), [HER2-amplified colorectal cancer](https://onco.cc/cancers/her2-amplified-colorectal/), [KRAS G12C-mutant colorectal cancer](https://onco.cc/cancers/kras-g12c-colorectal/), [Rectal cancer](https://onco.cc/cancers/rectal-cancer/)
- targets: [BRAF](https://onco.cc/targets/braf/), [EGFR](https://onco.cc/targets/egfr/)
- terms: [Anti-EGFR rechallenge](https://onco.cc/terms/anti-egfr-rechallenge/), [Consensus molecular subtypes (CMS1-4)](https://onco.cc/terms/cms-subtypes/), [Conversion therapy in bowel cancer](https://onco.cc/terms/conversion-therapy-colorectal/), [CpG island methylator phenotype (CIMP)](https://onco.cc/terms/cimp/), [Extended RAS testing](https://onco.cc/terms/extended-ras-testing/), [HERACLES criteria (HER2 in bowel cancer)](https://onco.cc/terms/heracles-criteria/), [Liver-limited metastatic bowel cancer](https://onco.cc/terms/liver-limited-metastatic-colorectal/)
- trials: [CAIRO5](https://onco.cc/trials/cairo5/), [CALGB/SWOG 80405](https://onco.cc/trials/calgb-80405/), [CRYSTAL & FIRE-3](https://onco.cc/trials/crystal-fire3/), [PARADIGM](https://onco.cc/trials/paradigm/), [PRIME](https://onco.cc/trials/prime/)
- key papers: [Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer (CRYSTAL)](https://onco.cc/key-papers/paper-van-cutsem-crystal-cetuximab-folfiri-nejm-2009/), [Classifying colorectal cancer by tumor location rather than sidedness highlights a continuum in mutation profiles and consensus molecular subtypes](https://onco.cc/key-papers/paper-loree-tumour-location-continuum-colorectal-ccr-2018/), [Clinical sequencing defines the genomic landscape of metastatic colorectal cancer](https://onco.cc/key-papers/paper-yaeger-metastatic-colorectal-genomic-landscape-cancer-cell-2018/), [Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features](https://onco.cc/key-papers/paper-missiaglia-distal-proximal-colon-cancers-ann-oncol-2014/), [Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in KRAS wild-type advanced or metastatic colorectal cancer (CALGB/SWOG 80405)](https://onco.cc/key-papers/paper-venook-calgb-80405-cetuximab-vs-bevacizumab-jama-2017/), [Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC)](https://onco.cc/key-papers/paper-kopetz-beacon-encorafenib-braf-colorectal-nejm-2019/), [FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3)](https://onco.cc/key-papers/paper-heinemann-fire-3-cetuximab-vs-bevacizumab-lancet-oncol-2014/), [Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up](https://onco.cc/key-papers/paper-esmo-metastatic-colorectal-cancer-guideline-ann-oncol-2023/), [Non-V600 BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer](https://onco.cc/key-papers/paper-jones-non-v600-braf-colorectal-jco-2017/), [Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial](https://onco.cc/key-papers/paper-paradigm-jama-2023/), [Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME)](https://onco.cc/key-papers/paper-douillard-prime-panitumumab-ras-nejm-2013/), [Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials](https://onco.cc/key-papers/paper-tejpar-tumour-location-crystal-fire3-jama-oncol-2017/), [Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials](https://onco.cc/key-papers/paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017/), [The consensus molecular subtypes of colorectal cancer](https://onco.cc/key-papers/paper-cms-guinney-nat-med-2015/), [The serrated pathway to colorectal carcinoma: current concepts and challenges](https://onco.cc/key-papers/paper-bettington-serrated-pathway-colorectal-histopathology-2013/)
- pairings: [Anti-EGFR antibody + chemotherapy in left-sided RAS/BRAF wild-type mCRC](https://onco.cc/pairings/anti-egfr-left-sided/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/)
- collections: [Colorectal Cancer Alliance](https://onco.cc/collections/colorectal-cancer-alliance/)
- biomarkers: [RAS wild-type (extended KRAS and NRAS testing)](https://onco.cc/biomarkers/ras-wild-type/)

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JSON: https://onco.cc/api/v1/entities/sidedness.json