Annals of Surgical Oncology

, Volume 26, Issue 5, pp 1366–1375 | Cite as

Oncologic Effects of Primary Tumor-Sidedness on Patients with Stages 1–3 Colon Cancer: A Meta-Analysis

  • Gi Won Ha
  • Jong Hun Kim
  • Min Ro LeeEmail author
Colorectal Cancer



Previous studies comparing the oncologic outcomes of primary tumor-sidedness for patients with colon cancer have reported a worse prognosis for those with right-sided tumors. However, most of these studies evaluated patients with metastatic disease.


PubMed, EMBASE, and the Cochrane Library were searched for studies that assessed the effects of primary tumor-sidedness on survival outcomes for patients with stages 1, 2, and 3 colon cancer. The hazard ratio (HR) for primary tumor location was estimated for overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS).


The inclusion criteria were met by 37 studies involving 581,542 patients. The patients with a right-sided tumor had better CSS (HR, 0.67; 95% confidence interval [CI], 0.56–0.80; p < 0.0001) among those with stage 1 cancer as well as better OS (HR, 0.89; 95% CI 0.86–0.92; I2 = 19%) and CSS (HR, 0.78; 95% CI 0.70–0.86; I2 = 78%) among those with stage 2 cancer. In contrast, among the patients with stage 3 cancer, those with a right-sided tumor had worse OS (HR, 1.12; 95% CI 1.04–1.20; p = 0.002), CSS (HR, 1.05; 95% CI 1.01–1.10; p = 0.02), and DFS (HR, 1.32; 95% CI 1.07–1.63; p = 0.008).


Primary tumor location may be a prognostic factor for patients with non-metastatic colon cancer. The prognosis for patients with right-sided tumor may be better for those with stage 1 or 2 cancer, but worse for those with stage 3 cancer.



There are no conflicts of interest.


  1. 1.
    Venook AP, Niedzwiecki D, Innocenti F, et al. Impact of primary tumor location on overall survival (OS) and progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC): analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol. 2016;34(Suppl 4S): 3504.CrossRefGoogle Scholar
  2. 2.
    Missiaglia E, Jacobs B, D’Ario G, et al. Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol. 2014;25:1995–2001.CrossRefGoogle Scholar
  3. 3.
    LaPointe LC, Dunne R, Brown GS, Worthley DL, Molloy PL, Wattchow D, Young GP. Map of differential transcript expression in the normal human large intestine. Physiol Genom. 2008;33:50–64.CrossRefGoogle Scholar
  4. 4.
    Guinney J, Dienstmann R, Wang X, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21:1350–6.CrossRefGoogle Scholar
  5. 5.
    Gervaz P, Bucher P, Morel P. Two colons—two cancers: paradigm shift and clinical implications. J Surg Oncol. 2004;88:261–6.CrossRefGoogle Scholar
  6. 6.
    Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–9.CrossRefGoogle Scholar
  7. 7.
    Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions. Version 5.1.0, vol. 5. Wiley, Chichester, United Kingdom, 2011.Google Scholar
  8. 8.
    Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Retrieved 1 Oct 2017 at
  9. 9.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.CrossRefGoogle Scholar
  10. 10.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.CrossRefGoogle Scholar
  11. 11.
    Thabane L, Akhtar-Danesh N. Guidelines for reporting descriptive statistics in health research. Nurse Res. 2008;15:72–81.CrossRefGoogle Scholar
  12. 12.
    Patsopoulos NA, Evangelou E, Ioannidis JP. Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation. Int J Epidemiol. 2008;37:1148–57.CrossRefGoogle Scholar
  13. 13.
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.CrossRefGoogle Scholar
  14. 14.
    Sutton AJ, Duval SJ, Tweedie RL, Abrams KR, Jones DR. Empirical assessment of effect of publication bias on meta-analyses. BMJ. 2000;320:1574–7.CrossRefGoogle Scholar
  15. 15.
    Brungs D, Aghmesheh M, de Souza P, et al. Sidedness is prognostic in locoregional colon cancer: an analysis of 9509 Australian patients. BMC Cancer. 2017;17:251.CrossRefGoogle Scholar
  16. 16.
    Karim S, Brennan K, Nanji S, Berry SR, Booth CM. Association between prognosis and tumor laterality in early-stage colon cancer. JAMA Oncol. 2017;3:1386–92.CrossRefGoogle Scholar
  17. 17.
    Lim DR, Kuk JK, Kim T, Shin EJ. Comparison of oncological outcomes of right-sided colon cancer versus left-sided colon cancer after curative resection: which side is better outcome? Med Baltim. 2017;96:e8241.CrossRefGoogle Scholar
  18. 18.
    Liu F, Li C, Jia H, et al. Is there a prognostic value of tumor location among Chinese patients with colorectal cancer? Oncotarget. 2017;8:38682–92.Google Scholar
  19. 19.
    Qin Q, Yang L, Sun YK, et al. Comparison of 627 patients with right- and left-sided colon cancer in China: differences in clinicopathology, recurrence, and survival. Chronic Dis Transl Med. 2017;3:51–9.CrossRefGoogle Scholar
  20. 20.
    Zhong M, Wu B, Xu L, Xiao Y, Lin G, Qiu H. Comparison of clinicopathologic features and survival between patients with right-sided and left-sided stage III colon cancer. Transl Cancer Res. 2017;6:254–60.CrossRefGoogle Scholar
  21. 21.
    Warschkow R, Sulz MC, Marti L, Tarantino I, Schmied BM, Cerny T, Güller U. Better survival in right-sided versus left-sided stage I–III colon cancer patients. BMC Cancer. 2016;16:554.CrossRefGoogle Scholar
  22. 22.
    Ahmadi O, Stringer MD, Black MA, McCall JL. Clinico-pathological factors influencing lymph node yield in colorectal cancer and impact on survival: analysis of New Zealand Cancer Registry data. J Surg Oncol. 2015;111:451–8.CrossRefGoogle Scholar
  23. 23.
    André T, de Gramont A, Vernerey D, et al. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 2015;33:4176–87.CrossRefGoogle Scholar
  24. 24.
    Gilardoni E, Bernasconi DP, Poli S, et al. Surveillance for early stages of colon cancer: potentials for optimizing follow-up protocols. World J Surg Oncol. 2015;13:260.CrossRefGoogle Scholar
  25. 25.
    Paquet ER, Cui J, Davidson D, et al. A 12-gene signature to distinguish colon cancer patients with better clinical outcome following treatment with 5-fluorouracil or FOLFIRI. J Pathol Clin Res. 2015;1:160–72.CrossRefGoogle Scholar
  26. 26.
    Pectasides D, Karavasilis V, Papaxoinis G, et al. Randomized phase III clinical trial comparing the combination of capecitabine and oxaliplatin (CAPOX) with the combination of 5-fluorouracil, leucovorin, and oxaliplatin (modified FOLFOX6) as adjuvant therapy inpatients with operated high-risk stage II or stage III colorectal cancer. BMC Cancer. 2015;15:384.CrossRefGoogle Scholar
  27. 27.
    Oue N, Anami K, Schetter AJ, et al. High miR-21 expression from FFPE tissues is associated with poor survival and response to adjuvant chemotherapy in colon cancer. Int J Cancer. 2014;134:1926–34.CrossRefGoogle Scholar
  28. 28.
    Renfro LA, Grothey A, Xue Y, et al. ACCENT-based web calculators to predict recurrence and overall survival in stage III colon cancer. J Natl Cancer Inst. 2014;106:1–9.CrossRefGoogle Scholar
  29. 29.
    Bhangu A, Kiran RP, Slesser A, Fitzgerald JE, Brown G, Tekkis P. Survival after resection of colorectal cancer based on anatomical segment of involvement. Ann Surg Oncol. 2013;20:4161–8.CrossRefGoogle Scholar
  30. 30.
    Gleisner AL, Mogal H, Dodson R, et al. Nodal status, number of lymph nodes examined, and lymph node ratio: what defines prognosis after resection of colon adenocarcinoma? J Am Coll Surg. 2013;217:1090–100.CrossRefGoogle Scholar
  31. 31.
    Lykke J, Roikjaer O, Jess P, Danish Colorectal Cancer Group. The relation between lymph node status and survival in stage I–III colon cancer: results from a prospective nationwide cohort study. Colorectal Dis. 2013;15:559–65.CrossRefGoogle Scholar
  32. 32.
    Kalady MF, Dejulius KL, Sanchez JA, et al. BRAF mutations in colorectal cancer are associated with distinct clinical characteristics and worse prognosis. Dis Colon Rectum. 2012;55:128–33.CrossRefGoogle Scholar
  33. 33.
    Katkoori VR, Shanmugam C, Jia X, et al. Prognostic significance and gene expression profiles of p53 mutations in microsatellite-stable stage III colorectal adenocarcinomas. PLoS One. 2012;7:e30020.CrossRefGoogle Scholar
  34. 34.
    van Steenbergen LN, Lemmens VE, Rutten HJ, Wymenga AN, Nortier JW, Janssen-Heijnen ML. Increased adjuvant treatment and improved survival in elderly stage III colon cancer patients in The Netherlands. Ann Oncol. 2012;23:2805–11.CrossRefGoogle Scholar
  35. 35.
    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;29:4401–9.CrossRefGoogle Scholar
  36. 36.
    Benedix F, Kube R, Meyer F, Schmidt U, Gastinger I, Lippert H, Colon/Rectum Carcinomas (Primary Tumor) Study Group. 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.CrossRefGoogle Scholar
  37. 37.
    Fariña-Sarasqueta A, van Lijnschoten G, Moerland E, Creemers GJ, Lemmens VE, Rutten HJ, van den Brule AJ. The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients. Ann Oncol. 2010;21:2396–402.CrossRefGoogle Scholar
  38. 38.
    Roth AD, Tejpar S, Delorenzi M, et al. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol. 2010;28:466–74.CrossRefGoogle Scholar
  39. 39.
    Deschoolmeester V, Van Damme N, Baay M, et al. Microsatellite instability in sporadic colon carcinomas has no independent prognostic value in a Belgian study population. Eur J Cancer. 2008;44:2288–95.CrossRefGoogle Scholar
  40. 40.
    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;15:2388–94.CrossRefGoogle Scholar
  41. 41.
    Burton S, Norman AR, Brown G, Abulafi AM, Swift RI. Predictive poor prognostic factors in colonic carcinoma. Surg Oncol. 2006;15:71–8.CrossRefGoogle Scholar
  42. 42.
    Sinicrope FA, Rego RL, Foster N, et al. Microsatellite instability accounts for tumor site-related differences in clinicopathologic variables and prognosis in human colon cancers. Am J Gastroenterol. 2006;101:2818–25.CrossRefGoogle Scholar
  43. 43.
    Wang B, Yang J, Li S, et al. Tumor location as a novel high-risk parameter for stage II colorectal cancers. PLoS One. 2017;12:e0179910.CrossRefGoogle Scholar
  44. 44.
    Ishihara S, Watanabe T, Akahane T, et al. 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;27:371–9.CrossRefGoogle Scholar
  45. 45.
    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;14:1493–9.CrossRefGoogle Scholar
  46. 46.
    Horst D, Kriegl L, Engel J, Jung A, Kirchner T. CD133 and nuclear beta-catenin: the marker combination to detect high-risk cases of low-stage colorectal cancer. Eur J Cancer. 2009;45:2034–40.CrossRefGoogle Scholar
  47. 47.
    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;95:2953–7.CrossRefGoogle Scholar
  48. 48.
    Jeong DH, Kim WR, Min BS, Kim YW, Song MK, Kim NK. Validation of a quantitative 12-multigene expression assay (Oncotype DX(®) Colon Cancer Assay) in Korean patients with stage II colon cancer: implication of ethnic differences contributing to differences in gene expression. Onco Targets Ther. 2015;8:3817–25.Google Scholar
  49. 49.
    Moritani K, Hasegawa H, Okabayashi K, Ishii Y, Endo T, Kitagawa Y. Difference in the recurrence rate between right- and left-sided colon cancer: a 17-year experience at a single institution. Surg Today. 2014;44:1685–91.CrossRefGoogle Scholar
  50. 50.
    Merok MA, Ahlquist T, Røyrvik EC, et al. Microsatellite instability has a positive prognostic impact on stage II colorectal cancer after complete resection: results from a large, consecutive Norwegian series. Ann Oncol. 2013;24:1274–82.CrossRefGoogle Scholar
  51. 51.
    Katoh H, Yamashita K, Wang G, Sato T, Nakamura T, Watanabe M. Prognostic significance of preoperative bowel obstruction in stage III colorectal cancer. Ann Surg Oncol. 2011;18:2432–41.CrossRefGoogle Scholar
  52. 52.
    Holch JW, Ricard I, Stintzing S, Modest DP, Heinemann V. The relevance of primary tumour location in patients with metastatic colorectal cancer: a meta-analysis of first-line clinical trials. Eur J Cancer. 2017;70:87–98.CrossRefGoogle Scholar
  53. 53.
    Arnold D, Lueza B, Douillard JY, et al. 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. 2017;28:1713–29.CrossRefGoogle Scholar
  54. 54.
    Yahagi M, Okabayashi K, Hasegawa H, Tsuruta M, Kitagawa Y. The worse prognosis of right-sided compared with left-sided colon cancers: a systematic review and meta-analysis. J Gastrointest Surg. 2016;20:648–55.CrossRefGoogle Scholar
  55. 55.
    Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol. 2005;23:609–18.CrossRefGoogle Scholar
  56. 56.
    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;10:917–23.Google Scholar
  57. 57.
    Jernvall P, Mäkinen MJ, Karttunen TJ, Mäkelä J, Vihko P. Microsatellite instability: impact on cancer progression in proximal and distal colorectal cancers. Eur J Cancer. 1999;35:197–201.CrossRefGoogle Scholar
  58. 58.
    Ribic CM, Sargent DJ, Moore MJ, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 2003;349:247–57.CrossRefGoogle Scholar
  59. 59.
    Kerr DJ, Domingo E, Kerr R. Is sidedness prognostically important across all stages of colorectal cancer? Lancet Oncol. 2016;17:1480–2.CrossRefGoogle Scholar
  60. 60.
    Fujiyoshi K, Yamamoto G, Takenoya T, et al. Metastatic pattern of stage IV colorectal cancer with high-frequency microsatellite instability as a prognostic factor. Anticancer Res. 2017;37:239–47.CrossRefGoogle Scholar
  61. 61.
    Kim CG, Ahn JB, Jung M, et al. Effects of microsatellite instability on recurrence patterns and outcomes in colorectal cancers. Br J Cancer. 2016;115:25–33.CrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  1. 1.Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University HospitalJeonjuSouth Korea

Personalised recommendations