Journal of Gastrointestinal Surgery

, Volume 20, Issue 3, pp 648–655 | Cite as

The Worse Prognosis of Right-Sided Compared with Left-Sided Colon Cancers: a Systematic Review and Meta-analysis

  • Masashi Yahagi
  • Koji OkabayashiEmail author
  • Hirotoshi Hasegawa
  • Masashi Tsuruta
  • Yuko Kitagawa
Original Article



Right-sided colon cancers (RCC) and left-sided colon cancers (LCC) are of different embryological origins, and various differences exist between them. However, the survival difference has not been assessed. The aim of this meta-analysis was to quantify the prognostic differences between RCC and LCC.


Fifteen studies that compared the prognosis of colon cancer according to tumor location were identified. The effects of tumor location on survival outcome were assessed.


Patients with RCC had a significantly worse prognosis than did those with LCC in overall survival (OS) (hazard ratio (HR) = 1.14, 95 % confidence interval (CI) 1.06–1.22, p < 0.01). Our subgroup analyses demonstrated significant prognostic differences in Western countries (HR = 1.15, 95 % CI 1.08–1.23, p < 0.01), a nationwide database (HR = 1.15, 95 % CI 1.05–1.27, p = 0.01), and a stage-adjusted analysis (HR = 1.14, 95 % CI 1.05–1.24, p < 0.01).


These findings demonstrate that tumor location is associated with prognosis in colorectal cancer patients, and those with RCC have a significantly worse prognosis than those with LCC in terms of OS. RCC should be treated distinctively from LCC, and the establishment of standardized management for colon cancer by tumor location is needed.


Prognosis Colon cancer Left-sided colon Right-sided colon 



The English in this document has been checked by at least two professional editors, both native speakers of English. For a certificate, please see:

Supplementary material

11605_2015_3026_MOESM1_ESM.doc (42 kb)
ESM 1 (DOC 42 kb)


  1. 1.
    Cucino C, Buchner AM, Sonnenberg A. Continued rightward shift of colorectal cancer. Dis Colon Rectum. 2002; 45: 1035-1040.CrossRefPubMedGoogle Scholar
  2. 2.
    Saltzstein SL, Behling CA. Age and time as factors in the left-to-right shift of the subsite of colorectal adenocarcinoma: a study of 213,383 cases from the California Cancer Registry. J Clin Gastroenterol. 2007; 41: 173-177.CrossRefPubMedGoogle Scholar
  3. 3.
    Gervaz P, Bucher P, Morel P. Two colons-two cancers: paradigm shift and clinical implications. J Surg Oncol. 2004; 88: 261-266.CrossRefPubMedGoogle Scholar
  4. 4.
    Bufill JA. Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location. Ann Intern Med. 1990; 113: 779-788.CrossRefPubMedGoogle Scholar
  5. 5.
    Birkenkamp-Demtroder K, Olesen SH, Sorensen FB, Laurberg S, Laiho P, Aaltonen LA, Orntoft TF. Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid. Gut. 2005; 54: 374-384.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Glebov OK, Rodriguez LM, Nakahara K, Jenkins J, Cliatt J, Humbyrd CJ, DeNobile J, Soballe P, Simon R, Wright G, Lynch P, Patterson S, Lynch H, Gallinger S, Buchbinder A, Gordon G, Hawk E, Kirsch IR. Distinguishing right from left colon by the pattern of gene expression. Cancer Epidemiol Biomarkers Prev. 2003; 12: 755-762.PubMedGoogle Scholar
  7. 7.
    Wiggers T, Arends JW, Volovics A. Regression analysis of prognostic factors in colorectal cancer after curative resections. Dis Colon Rectum. 1988; 31: 33-41.CrossRefPubMedGoogle Scholar
  8. 8.
    Steinberg SM, Barkin JS, Kaplan RS, Stablein DM. Prognostic indicators of colon tumors. The Gastrointestinal Tumor Study Group experience. Cancer. 1986; 57: 1866-1870.CrossRefPubMedGoogle Scholar
  9. 9.
    Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010; 8: 336-341.CrossRefPubMedGoogle Scholar
  10. 10.
    Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010; 25: 603-605.CrossRefPubMedGoogle Scholar
  11. 11.
    Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007; 8: 16.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994; 50: 1088-1101.CrossRefPubMedGoogle Scholar
  13. 13.
    Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21: 1539-1558.CrossRefPubMedGoogle Scholar
  14. 14.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Bmj. 2003; 327: 557-560.PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Otani T, Yoshimatsu K, Yokomizo H, Fujimoto T, Umehara A, Matsumoto A, Osawa G, Itagaki H, Yano Y, Ogawa K. Clinicopathological differences between proximal and distal pT3 colon cancer and the clinical significance of the depth of cancer invasion beyond the muscularis propria. Hepatogastroenterology. 2012; 59: 395-399.PubMedGoogle Scholar
  16. 16.
    Tentes AA, Korakianitis OS, Kakolyris S, Veliovits D, Fotakis S, Kouyioumtzi I, Kyziridis D. Differences between right- and left-sided colon carcinomas. J buon. 2010; 15: 285-289.PubMedGoogle Scholar
  17. 17.
    Ishihara S, Watanabe T, Akahane T, Shimada R, Horiuchi A, Shibuya H, Hayama T, Yamada H, Nozawa K, Matsuda K, Maeda K, Sugihara K. Tumor location is a prognostic factor in poorly differentiated adenocarcinoma, mucinous adenocarcinoma, and signet-ring cell carcinoma of the colon. Int J Colorectal Dis. 2012; 27: 371-379.CrossRefPubMedGoogle Scholar
  18. 18.
    Derwinger K, Gustavsson B. Variations in demography and prognosis by colon cancer location. Anticancer Res. 2011; 31: 2347-2350.PubMedGoogle Scholar
  19. 19.
    Bleeker WA, Hayes VM, Karrenbeld A, Hofstra RM, Hermans J, Buys CC, Plukker JT. Impact of KRAS and TP53 mutations on survival in patients with left- and right-sided Dukes’ C colon cancer. Am J Gastroenterol. 2000; 95: 2953-2957.CrossRefPubMedGoogle Scholar
  20. 20.
    Wray CM, Ziogas A, Hinojosa MW, Le H, Stamos MJ, Zell JA. Tumor subsite location within the colon is prognostic for survival after colon cancer diagnosis. Dis Colon Rectum. 2009; 52: 1359-1366.CrossRefPubMedGoogle Scholar
  21. 21.
    Burton S, Norman AR, Brown G, Abulafi AM, Swift RI. Predictive poor prognostic factors in colonic carcinoma. Surg Oncol. 2006; 15: 71-78.CrossRefPubMedGoogle Scholar
  22. 22.
    Benedix F, Kube R, Meyer F, Schmidt U, Gastinger I, Lippert H, Colon/Rectum Carcinomas Study G. Comparison of 17,641 patients with right- and left-sided colon cancer: differences in epidemiology, perioperative course, histology, and survival. Dis Colon Rectum. 2010; 53: 57-64.CrossRefPubMedGoogle Scholar
  23. 23.
    Suttie SA, Shaikh I, Mullen R, Amin AI, Daniel T, Yalamarthi S. Outcome of right- and left-sided colonic and rectal cancer following surgical resection. Colorectal Dis. 2011; 13: 884-889.CrossRefPubMedGoogle Scholar
  24. 24.
    Deschoolmeester V, Van Damme N, Baay M, Claes K, Van Marck E, Baert FJ, Wuyts W, Cabooter M, Weyler J, Vermeulen P, Lardon F, Vermorken JB, Peeters M. Microsatellite instability in sporadic colon carcinomas has no independent prognostic value in a Belgian study population. Eur J Cancer. 2008; 44: 2288-2295.CrossRefPubMedGoogle Scholar
  25. 25.
    Sinicrope FA, Rego RL, Foster N, Sargent DJ, Windschitl HE, Burgart LJ, Witzig TE, Thibodeau SN. Microsatellite instability accounts for tumor site-related differences in clinicopathologic variables and prognosis in human colon cancers. Am J Gastroenterol. 2006; 101: 2818-2825.CrossRefPubMedGoogle Scholar
  26. 26.
    Krajewska M, Kim H, Kim C, Kang H, Welsh K, Matsuzawa S, Tsukamoto M, Thomas RG, Assa-Munt N, Piao Z, Suzuki K, Perucho M, Krajewski S, Reed JC. Analysis of apoptosis protein expression in early-stage colorectal cancer suggests opportunities for new prognostic biomarkers. Clin Cancer Res. 2005; 11: 5451-5461.CrossRefPubMedGoogle Scholar
  27. 27.
    Bae JM, Kim JH, Cho NY, Kim TY, Kang GH. Prognostic implication of the CpG island methylator phenotype in colorectal cancers depends on tumour location. Br J Cancer. 2013; 109: 1004-1012.PubMedCentralCrossRefPubMedGoogle Scholar
  28. 28.
    Shepherd JM, Jones JS. Adenocarcinoma of the large bowel. Br J Cancer. 1971; 25: 680-690.PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Powell AG, Wallace R, McKee RF, Anderson JH, Going JJ, Edwards J, Horgan PG. The relationship between tumour site, clinicopathological characteristics and cancer-specific survival in patients undergoing surgery for colorectal cancer. Colorectal Dis. 2012; 14: 1493-1499.CrossRefPubMedGoogle Scholar
  30. 30.
    Hansen IO, Jess P. Possible better long-term survival in left versus right-sided colon cancer - a systematic review. Dan Med J. 2012; 59: A4444.PubMedGoogle Scholar
  31. 31.
    Roncucci L, Fante R, Losi L, Di Gregorio C, Micheli A, Benatti P, Madenis N, Ganazzi D, Cassinadri MT, Lauriola P, Ponz de Leon M. Survival for colon and rectal cancer in a population-based cancer registry. Eur J Cancer. 1996; 32a: 295-302.CrossRefPubMedGoogle Scholar
  32. 32.
    Sariego J, Byrd ME, Kerstein M, Sano C, Matsumoto T. Changing patterns in colorectal carcinoma: a 25-year experience. Am Surg. 1992; 58: 686-691.PubMedGoogle Scholar
  33. 33.
    Weiss JM, Pfau PR, O’Connor ES, King J, LoConte N, Kennedy G, Smith MA. Mortality by stage for right- versus left-sided colon cancer: analysis of surveillance, epidemiology, and end results--Medicare data. J Clin Oncol. 2011; 29: 4401-4409.PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Meguid RA, Slidell MB, Wolfgang CL, Chang DC, Ahuja N. Is there a difference in survival between right- versus left-sided colon cancers? Ann Surg Oncol. 2008; 15: 2388-2394.PubMedCentralCrossRefPubMedGoogle Scholar
  35. 35.
    Iacopetta B. Are there two sides to colorectal cancer? Int J Cancer. 2002; 101: 403-408.CrossRefPubMedGoogle Scholar
  36. 36.
    Nawa T, Kato J, Kawamoto H, Okada H, Yamamoto H, Kohno H, Endo H, Shiratori Y. Differences between right- and left-sided colon cancer in patient characteristics, cancer morphology and histology. J Gastroenterol Hepatol. 2008; 23: 418-423.CrossRefPubMedGoogle Scholar
  37. 37.
    Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008; 58: 71-96.CrossRefPubMedGoogle Scholar
  38. 38.
    Hohenberger W, Weber K, Matzel K, Papadopoulos T, Merkel S. Standardized surgery for colonic cancer: complete mesocolic excision and central ligation--technical notes and outcome. Colorectal Dis. 2009; 11: 354-364; discussion 364-355.CrossRefPubMedGoogle Scholar
  39. 39.
    West NP, Morris EJ, Rotimi O, Cairns A, Finan PJ, Quirke P. Pathology grading of colon cancer surgical resection and its association with survival: a retrospective observational study. Lancet Oncol. 2008; 9: 857-865.CrossRefPubMedGoogle Scholar
  40. 40.
    Spasojevic M, Stimec BV, Dyrbekk AP, Tepavcevic Z, Edwin B, Bakka A, Ignjatovic D. Lymph node distribution in the d3 area of the right mesocolon: implications for an anatomically correct cancer resection. A postmortem study. Dis Colon Rectum. 2013; 56: 1381-1387.CrossRefPubMedGoogle Scholar
  41. 41.
    Akiyoshi T, Kuroyanagi H, Fujimoto Y, Konishi T, Ueno M, Oya M, Yamaguchi T. Short-term outcomes of laparoscopic colectomy for transverse colon cancer. J Gastrointest Surg. 2010; 14: 818-823.CrossRefPubMedGoogle Scholar
  42. 42.
    West NP, Kobayashi H, Takahashi K, Perrakis A, Weber K, Hohenberger W, Sugihara K, Quirke P. Understanding optimal colonic cancer surgery: comparison of Japanese D3 resection and European complete mesocolic excision with central vascular ligation. J Clin Oncol. 2012; 30: 1763-1769.CrossRefPubMedGoogle Scholar
  43. 43.
    Lanza G, Jr., Maestri I, Ballotta MR, Dubini A, Cavazzini L. Relationship of nuclear DNA content to clinicopathologic features in colorectal cancer. Mod Pathol. 1994; 7: 161-165.PubMedGoogle Scholar
  44. 44.
    Soreide K, Janssen EA, Soiland H, Korner H, Baak JP. Microsatellite instability in colorectal cancer. Br J Surg. 2006; 93: 395-406.CrossRefPubMedGoogle Scholar
  45. 45.
    Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol. 2005; 23: 609-618.CrossRefPubMedGoogle Scholar
  46. 46.
    Samowitz WS, Curtin K, Ma KN, Schaffer D, Coleman LW, Leppert M, Slattery ML. Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level. Cancer Epidemiol Biomarkers Prev. 2001; 10: 917-923.PubMedGoogle Scholar
  47. 47.
    Jernvall P, Makinen MJ, Karttunen TJ, Makela J, Vihko P. Microsatellite instability: impact on cancer progression in proximal and distal colorectal cancers. Eur J Cancer. 1999; 35: 197-201.CrossRefPubMedGoogle Scholar
  48. 48.
    Loupakis F, Yang D, Yau L, Feng S, Cremolini C, Zhang W, Maus MK, Antoniotti C, Langer C, Scherer SJ, Muller T, Hurwitz HI, Saltz L, Falcone A, Lenz HJ. Primary tumor location as a prognostic factor in metastatic colorectal cancer. J Natl Cancer Inst. 2015; 107.Google Scholar
  49. 49.
    von Einem JC, Heinemann V, von Weikersthal LF, Vehling-Kaiser U, Stauch M, Hass HG, Decker T, Klein S, Held S, Jung A, Kirchner T, Haas M, Holch J, Michl M, Aubele P, Boeck S, Schulz C, Giessen C, Stintzing S, Modest DP. 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. 2014; 140: 1607-1614.CrossRefGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2015

Authors and Affiliations

  • Masashi Yahagi
    • 1
  • Koji Okabayashi
    • 1
    Email author
  • Hirotoshi Hasegawa
    • 1
  • Masashi Tsuruta
    • 1
  • Yuko Kitagawa
    • 1
  1. 1.Department of SurgeryKeio University School of MedicineTokyoJapan

Personalised recommendations