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Right versus left-sided colon cancer: Is it time to consider these as different diseases?

Guy’s Cancer Centre, Guy’s and St Thomas’ NHS Foundation Trust, Management Offices, 4th Floor Bermondsey Wing, Great Maze Pond, London SE1 9RT

Primary tumour location has emerged as an important characteristic in understanding the outcomes for patients with colorectal cancer. Recent international re-appraisal of randomised controlled data as well as case series and epidemiological databases clearly demonstrate that primary tumour location is both an independent prognostic marker and has predictive value in relation to anti-EGFR therapy. Consequently, location should be taken into consideration in the clinical management of patients affected by colon cancer as well as informing research and the design of future clinical trials.
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Keywords primary tumour location; metastatic colorectal cancer; sidedness; prognostic; predictive; molecular signature; stratification

Citation: Paul J Ross, Krishnie Srikandarajah, Julien de Naurois. Right versus left-sided colon cancer: Is it time to consider these as different diseases?. AIMS Medical Science, 2018, 5(3): 303-315. doi: 10.3934/medsci.2018.3.303


  • 1. Venook AP (2017) Right-sided vs left-sided colorectal cancer. Clin Adv Hematol Oncol 15: 22–24.
  • 2. Venook AP, Niedzwiecki D, Innocenti F, et al. (2016) Impact of primary (1o) tumor location on overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol 34 (suppl; abstr 3504). Available from: http://meetinglibrary.asco.org/content/161936-176.
  • 3. Meguid RA, Slidell MB, Wolfgang CL, et al. (2008) Is There a Difference in Survival Between Right-Versus Left-Sided Colon Cancers? Ann Surg Oncol 15: 2388–2394.    
  • 4. Benedix F, Kube R, Meyer F, et al. (2010) Comparison of 17,641 patients with right- and left-sided colon cancer: Differences in epidemiology, perioperative course, histology, and survival. Dis Colon Rectum 53: 57–64.    
  • 5. Price TJ, Beeke C, Ullah S, et al. (2015) Does the primary site of colorectal cancer impact outcomes for patients with metastatic disease? Cancer 121: 830–835.    
  • 6. Petrelli F, Tomasello G, Borgo K, et al. (2017) Prognostic survival associated with left-sided vs right-sided colon cancer a systematic review and meta-analysis. JAMA Oncol 3: 211–219.    
  • 7. O'Dwyer PJ, Manola J, Valone FH, et al. (2001) Fluorouracil modulation in colorectal cancer: Lack of improvement with N-phosphonoacetyl-l-aspartic acid or oral leucovorin or interferon, but enhanced therapeutic index with weekly 24-hour infusion schedule- an Eastern Cooperative Oncology Group/Cancer and Leukemia Group B study. J Clin Oncol 19: 2413–2421.    
  • 8. Bufill JA (1990) Colorectal cancer: Evidence for distinct genetic categories based on proximal or distal tumor location. Ann Int Med 113: 779–788.    
  • 9. Iacopetta B (2002) Are there two sides to colorectal cancer? Int J Cancer 101: 403–408.    
  • 10. Gervaz P, Bucher P, Morel P (2004) Two colons-two cancers: Paradigm shift and clinical implications. J Surg Oncol 88: 261–266.    
  • 11. Bae JM, Kim JH, Cho NY, et al. (2013) Prognostic implication of the CpG island methylator phenotype in colorectal cancers depends on tumour location. Br J Cancer 109: 1004–1012.    
  • 12. Yamauchi M, Morikawa T, Kuchiba A, et al. (2012) Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum. Gut 61: 847–854.    
  • 13. Toyota M, Ahuja N, Ohe-Toyota M, et al. (1999) CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A 96: 8681–8686.    
  • 14. Weisenberger DJ, Siegmund KD, Campan M, et al. (2006) CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet 38: 787–793.    
  • 15. Roepman P, Schlicker A, Taberner J, et al. (2013) Colorectal cancer intrinsic subtypes predict chemotherapy benefit, deficient mismatch repair and epithelial-to-mesenchymal transition. Int J Cancer 134: 552–562.
  • 16. Marisa L, de Reynies A, Duval A, et al. (2013) Gene expression classification of colon cancer into molecular subtypes: Characterization, validation, and prognostic value. PLoS Med 10: e1001453.    
  • 17. Guinney J, Dienstmann R, Xang X, et al. (2016) The consensus molecular subtypes of colorectal cancer. Nat Med 21: 1350–1356.
  • 18. De SEMF, Wang X, Jasen M, et al. (2013) Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions. Nat Med 19: 614–618.    
  • 19. Perez-Villamil B, Romera-Lopez A, Hernandez-Prieto S, et al. (2012) Colon cancer molecular subtypes identified by expression profiling and associated to stroma, mucinous type and different clinical behavior. BMC Cancer 12: 1–13.    
  • 20. Sadanandam A, Lyssiotis CA, Homicsko K, et al. (2013) A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nat Med 19: 619–625.    
  • 21. Loree JM, Pereira AA, Lam M, el al. (2018) Classifying colorectal cancer by tumor location rather than sidedness highlights a continuum in mutation profiles and Consensus Molecular Subtypes. Clin Cancer Res 24: 1062–1072.    
  • 22. Yothers H, O'Connell MJ, Allegra CJ, et al. (2011) Oxaliplatin as adjuvant therapy for colon cancer: Updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol 29: 3768–3774.    
  • 23. Kim SR, Song N, Yothers G, et al. (2018) Tumor sidedness and intrinsic subtypes in patients with stage II/III colon cancer: Analysis of NSABP C-07 (NRG Oncology). Br J Cancer 118: 629–633.    
  • 24. Song N, Poguegeile KL, Gavin PG, et al. (2017) Clinical Outcome from oxaliplatin treatment in stage II/III colon cancer according to intrinsic subtypes: Secondary analysis of NSABP C-07/NRG Oncology Randomized Clinical Trial. JAMA Oncol 2: 1162–1169.
  • 25. Lenz HJ, Ou FZ, Venook AP, et al. (2017) Impact of consensus molecular subtyping (CMS) on overall survival (OS) and progression free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol 35: 3511–3511.
  • 26. Elsaleh H, Joseph D, Grieu F, et al. (2000) Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer. Lancet 355: 1745–1750.    
  • 27. Sinicrope FA, Foster NR, Thibodeau SN, et al. (2011) DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy. J Natl Cancer Inst 103: 863–875.    
  • 28. Sinicrope FA, Foster NR, Thibodeau SN, et al. (2013) Prognostic impact of deficient DNA mismatch repair in patients with stage III colon cancer from a randomized trial of FOLFOX-based adjuvant chemotherapy. J Clin Oncol 31: 3664–3672.    
  • 29. Hutchins G, Southward K, Handley K, et al. (2011) Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. J Clin Oncol 29: 1261–1270.    
  • 30. Venook AP, Ou F, Lenz H, et al. (2017) Primary (1°) tumor location as an independent prognostic marker from molecular features for overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol 35: 3503
  • 31. Einem JCV, Heinemann V, Weikersthal LFV, et al. (2014) Left-sided primary tumors are associated with favorable prognosis in patients with KRAS codon 12/13 wild-type metastatic colorectal cancer treated with cetuximab plus chemotherapy: An analysis of the AIO KRK-0104 trial. J Cancer Res Clin Oncol 140: 1607–1614.    
  • 32. Heinemann V, von Weikersthal LF, Decker T, et al. (2014) FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): A randomised, open-label, phase 3 trial. Lancet Oncol 15: 1065–1075.    
  • 33. Schwartzberg LS, Rivera F, Karthaus M, et al. (2014) PEAK: A randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal. J Clin Oncol 32: 2240–2247.    
  • 34. Arnold D, Lueza B, Douillard JY, et al. (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. Ann Oncol 28: 1713–1729.    
  • 35. Holch JW, Ricard I, Stintzing S, et al. (2017) The relevance of primary tumour location in patients with metastatic colorectal cancer: A meta-analysis of first-line clinical trials. Eur J Cancer 70: 87–98.    
  • 36. Modest DP, Stintzing S, Weikersthal LFV, et al. (2017) Exploring the effect of primary tumor sidedness on therapeutic efficacy across treatment lines in patients with metastatic colorectal cancer: Analysis of FIRE-3 (AIOKRK0306). Oncotarget 8: 105749–105760.
  • 37. Jonker DJ, O'Callaghan CJ, Karapetis C, et al. (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357: 2040–2048.    
  • 38. Brulé SY, Jonker DJ, Karapetis CS, et al. (2015) Location of colon cancer (right-sided versus left-sided) as a prognostic factor and a predictor of benefit from cetuximab in NCIC CO.17. Eur J Cancer 51: 1405–1414.    
  • 39. Hurwitz H, Fehrenbacher L, Novotny W, et al. (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350: 2335–2342.    
  • 40. Saltz LB, Clarke S, Diaz-Rubio E, et al. (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: A randomized phase III study. J Clin Oncol 26: 2013–2019.    
  • 41. Loupakis F, Yang D, Yau L, et al. (2015) Primary tumor location as a prognostic factor in metastatic colorectal cancer. J Natl Cancer Inst 107: 1–9.
  • 42. Tebbutt NC, Wilson K, Gebski V, et al. (2010) Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: Results of the Australasian Gastrointestinal Trials Group randomized phase III MAX study. J Clin Oncol 28: 3191–3198.    
  • 43. Price TJ, Buizen L, Hardingham J (2014) Molecular subgroups from the AGITG MAX trial; right or left primary site of colorectal cancer and outcomes for metastatic colorectal cancer (mCRC). Ann Oncol 25: iv167–iv209.
  • 44. Wirapati P, Pomella V, Vandenbosch B, et al. (2017) Velour trial biomarkers update: Impact of RAS, BRAF, and sidedness on aflibercept activity. J Clin Oncol 35: 3538.    
  • 45. Ishikawa T, Fujita T, Suzuki Y, et al. (2003) Tumor-specific immunological recognition of frameshift-mutated peptides in colon cancer with microsatellite instability. Cancer Res 63: 5564–5572.
  • 46. Le DT (2015) PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 372: 2509–2520.    
  • 47. Le DT, Durham JN, Smith KN, et al. (2017) Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357: 409–413.    
  • 48. Dupré A, Malik HZ, Jones RP, et al. (2018) Influence of the primary tumour location in patients undergoing surgery for colorectal liver metastases. Eur J Surg Oncol 44: 80–86.    
  • 49. Lee H, Choi DW, Cho YB, et al. (2014) Recurrence pattern depends on the location of colon cancer in the patients with synchronous colorectal liver metastasis. Ann Surg Oncol 21: 1641–1646.    
  • 50. Cho JH, Hamaji M, Allen MS, et al. (2014) The prognosis of pulmonary metastasectomy depends on the location of the primary colorectal cancer. Ann Thorac Surg 98: 1231–1237.    
  • 51. van Hazel G, Heinemann V, Sharma N, et al. (2017) Impact of primary tumour location on survival for 1st line SIRT. Ann Oncol 28: 152.
  • 52. Sharma RA, Wasan HS, van Hazel GA, et al. (2017) Overall survival analysis of the FOXFIRE prospective randomized studies of first-line selective internal radiotherapy (SIRT) in patients with liver metastases from colorectal cancer. J Clin Oncol 35: 3507–3507.
  • 53. Wasan HS, Sharma RA, Heinemann V, et al. (2017) LBA26FOXFIRE-SIRFLOX-FOXFIRE global prospective randomised studies of first-line selective internal radiotherapy (SIRT) in patients with liver metastases from colorectal cancer: KRAS mutation and tumour site analysis. Ann Oncol 28: v605–v649.


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