International Journal of Colorectal Disease

, Volume 28, Issue 10, pp 1377–1384 | Cite as

An appraisal of lymph node ratio in colon and rectal cancer: not one size fits all

  • M. Medani
  • Niall Kelly
  • George Samaha
  • G. Duff
  • Vourneen Healy
  • Elizabeth Mulcahy
  • Eoghan Condon
  • David Waldron
  • Jean Saunders
  • J. Calvin CoffeyEmail author
Original Article



Lymph node ratio (LNR) is increasingly accepted as a useful prognostic indicator in colorectal cancer. However, variations in methodology, statistical stringency and cohort composition has led to inconsistency in respect of the optimally prognostic LNR.


The aim was to apply a robust regression-based analysis to generate and appraise LNRs optimally prognostic for colon and rectal cancer, both separately and in combination.


LNR was established for all patients undergoing either a colonic (n = 379) or rectal (n = 160) cancer resection with curative intent. The optimal LNR associated with disease-free and overall survival were established using a classification and regression tree technique. This process was repeated separately for patients who underwent either colonic or rectal resection and for the combined cohort. Survival associated with differing LNR was estimated using the Kaplan–Meier method and compared using a log-rank test. Relationships between LNR, disease-free survival (DFS) and overall survival (OS) were further characterised using Cox regression analysis. All statistical analyses were conducted in the R programming environment, with statistical significance was taken at a level of p < 0.05.


Optimal LNRs differed between each cohort, when either overall or disease-free survival was considered. LNRs generated from combined cohorts also differed from those generated by individual cohorts. In relation to DFS, LNR values were obtained and included 0.18 for the colon cancer cohort and 0.19 for the rectal and combined colorectal cancer cohorts. In relation to OS, multiple LNR values were obtained for colon and combined cohorts; however, an optimal LNR was not evident in the rectal cancer cohort. Survival patterns according to LNR closely resembled those associated with standard nodal staging.


Application of a data-driven approach based on recursive partitioning generates differing lymph node ratios for colon, rectal and combined colorectal cohorts. In each cohort, LNR was similarly prognostic to standard nodal staging in respect to overall and disease-free survival. Overall survival was associated with a multiplicity of LNR values, whilst disease-free survival was associated with a single LNR only. The paper demonstrates the merits of utilising a data-driven approach to determining lymph node ratios from specific patient cohorts. Utilising such an approach enabled the generation of those LNRs that were most associated with particular survival trends in relation to overall and disease-free survival. These differed markedly for colon cancer, rectal cancer and combined cohorts. In general, the survival patterns associated with LNRs generated were similar to those observed with standard nodal staging.


Colon Rectum Cancer Survival Lymph node ratio 


Sources of funding

There were no sources of funding for this publication.

Supplementary material

384_2013_1707_MOESM1_ESM.docx (12 kb)
ESM 1 (DOCX 11 kb)


  1. 1.
    Baxter NN, Virnig DJ, Rothenberger DA et al (2005) Lymph node evaluation in colorectal cancer patients: a population-based study. J Natl Cacner Inst 97(3):219–225CrossRefGoogle Scholar
  2. 2.
    Culligan K et al (2012) The mesocolon: a prospective observational study. Colorectal Dis 14(4):421–428, discussion 428–30PubMedCrossRefGoogle Scholar
  3. 3.
    Culligan K et al (2012) Review of nomenclature in colonic surgery - Proposal of a standardised nomenclature based on mesocolic anatomy. SurgeonGoogle Scholar
  4. 4.
    Kim YS, Kim JH, Yoon SM et al (2009) Lymph node ratio as a prognostic factor in patients with stage III rectal cancer treated with total mesorectal excision followed by chemoradiotherapy. Int J Radiat Oncol Biol Phys 74:796–802PubMedCrossRefGoogle Scholar
  5. 5.
    Berger AC, Sigurdson ER, LeVoyer T, Hanlon A, Mayer RJ, Macdonald JS, Catalano PJ, Haller DG (2005) Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes. J Clin Oncol 23(34):8706–8712PubMedCrossRefGoogle Scholar
  6. 6.
    Elias E, Mukherji D, Faraj W, Khalife M, Dimassi H, Eloubeidy M, Hattoum H, Alfa GA, Melki C, Shamseddine A (2012) Lymph node ratio is an independent prognostic factor in Stage III colorectal cancer patients: a retrospective study from the Middle East. World J Surg Oncol 10(1):63PubMedCrossRefGoogle Scholar
  7. 7.
    Greenberg R, Itah R, Ghinea R, Sacham-Shmueli E, Inbar R, Avital S (2011) Metastatic lymph node ratio (LNR) as a prognostic variable in colorectal cancer patients undergoing laparoscopic resection. Tech Coloproctol 15(3):273–279PubMedCrossRefGoogle Scholar
  8. 8.
    Lee HY, Choi HJ, Park KJ et al (2007) Prognostic significance of metastatic lymph node ratio in node-positive colon carcinoma. Ann Surg Oncol 14:1712–1717PubMedCrossRefGoogle Scholar
  9. 9.
    Park YH, Lee JI Park JK, Jo HJ, Kang WK, An CH (2011) Clinical significance of lymph node ratio in stage III colorectal cancer. J Korean Soc Coloproctol 27(5):260–265PubMedCrossRefGoogle Scholar
  10. 10.
    Peng J, Xu Y, Guan Z, Zhu J, Wang M, Cai G, Sheng W, Cai S (2008) Prognostic significance of the metastatic lymph node ratio in node-positive rectal cancer. Ann Surg Oncol 15(11):3118–3123PubMedCrossRefGoogle Scholar
  11. 11.
    Qui HB, Zhang LY, Li YF, Zhou ZW, Keshari RP, Xu RH (2011) Ratio of metastatic to resected lymph nodes enhances to predict survival in patients with stage III colorectal cancer. Ann Surg Oncol 18(6):1568–1574CrossRefGoogle Scholar
  12. 12.
    Rosenberg R, Engel J, Bruns C, Heitland W, Hermes N, Jauch KW, Kopp R, Pütterich E, Ruppert R, Schuster T, Friess H, Hölzel D (2010) The prognostic value of lymph node ratio in a population-based collective of colorectal cancer patients. Ann Surg 251(6):1070–1078PubMedCrossRefGoogle Scholar
  13. 13.
    Rosenberg R, Friederichs J, Schuster T et al (2008) Prognosis of patients with colorectal cancer is associated with lymph node ratio: a single-centre analysis of 3,026 patients over a 25-year time period. Ann Surg 248(6):968–978PubMedCrossRefGoogle Scholar
  14. 14.
    Schumacher P, Dineen S, Branett C Jr et al (2007) The metastatic lymph node ration predicts survival in colon cancer. Am J Surg 194:827–832PubMedCrossRefGoogle Scholar
  15. 15.
    Shao XL, Han HQ, He XL, Fu Q, Ly YC, Liu G (2011) Impact of number of retrieved lymph nodes and lymph node ratio on the prognosis in patients with stage II and III colorectal cancer. Zhonghua Wei Chang Wai Ke Za Zhi 14(4):249–253PubMedGoogle Scholar
  16. 16.
    Tong LL, Gao P, Wang ZN, Song YX, Xu YY, Sun Z, Xing CZ, Wang X, Xu HM (2011) Can lymph node ratio take the place of pN categories in the UICC/AJCC TNM classification system for colorectal cancer? Ann Surg Oncol 18(9):2453–2460PubMedCrossRefGoogle Scholar
  17. 17.
    Vaccaro CA, Im V, Rossi GL, Quintana GO, Benati ML, PerezdeArenaza D, Bonadeo FA (2009) Lymph node ratio as prognosis factor for colon cancer treated by colorectal surgeons. Dis Colon Rectum 52(7):1244–1250PubMedCrossRefGoogle Scholar
  18. 18.
    Wang J, Hassett JM, Dayton MT, Kulaylat MN (2008) Lymph node ratio: role in the staging of node-positive colon cancer. Ann Surg Oncol 15:1600–1608PubMedCrossRefGoogle Scholar
  19. 19.
    Ceelen W, Van Nieuwenhove Y, Pattyn P (2010) Prognostic value of the lymph node ratio in stage III colorectal cancer: a systematic review. Ann Surg Oncol 17(11):2847–2855PubMedCrossRefGoogle Scholar
  20. 20.
    Bujko K, Nowacki MP, Nasierowska-Guttmejer A et al (2005) Prediction of mesorectal nodal metastases after chemoradiation for rectal cancer: results of a randomised trial: implication for subsequent local excision. Radiother Oncol 76(3):234–240PubMedCrossRefGoogle Scholar
  21. 21.
    Doll D, Gertler R, Maak M et al (2009) Reduced lymph node yield in rectal carcinoma specimen after neoadjuvant radiochemotherapy has no prognostic relevance. World J Surg 33(2):340–347PubMedCrossRefGoogle Scholar
  22. 22.
    Latkauskas T, Lizdenis P, Janciauskiene R et al (2010) Lymph node retrieval after resection of rectal cancer following preoperative chemoradiotherapy. Medicina (Kaunas) 46(5):299–304Google Scholar
  23. 23.
    Habr-Gama A et al (2008) Absence of lymph nodes in the resected specimen after radical surgery for distal rectal cancer and neoadjuvant chemoradiation therapy: what does it mean? Dis Colon Rectum 51(3):277–283PubMedCrossRefGoogle Scholar
  24. 24.
    Samowitz WS et al (2000) Relationship of K-ras mutations in colon cancers to tumour location, stage and survival: a population-based study. Cancer Epidemiol Biomarkers Prev 9(11):1193–1197PubMedGoogle Scholar
  25. 25.
    Kaji E et al (2011) Analysis of Kras, BRAF and PIK3CA mutations in laterally-spreading tumours of the colorectum. J Gastroenterol Hepatol 26(3):599–607PubMedCrossRefGoogle Scholar
  26. 26.
    Zlobec I et al (2010) Combined analysis of specific KRAS mutation, BRAF and microsatellite instability identifies prognostic subgroups of sporadic and hereditary colorectal cancer. Int J Cancer 127(11):2569–2575PubMedCrossRefGoogle Scholar
  27. 27.
    Elnatan J, Goh HS, Smith DR (1996) C-KI-RAS activation and the biological behaviour of proximal and distal colonic adenocarcinomas. Eur J Cancer 32A(3):491–497PubMedCrossRefGoogle Scholar
  28. 28.
    Greene FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller DG, Morrow M (2002) The AJCC Cancer Staging Manual, 6th edn. Springer, New York, pp 113–124CrossRefGoogle Scholar
  29. 29.
    Cohen AM, Tremiterra S, Candela F et al (1991) Prognosis of node-positive colon cancer. Cancer 67(7):1859–1861PubMedCrossRefGoogle Scholar
  30. 30.
    Mekenkamp LJ, van Krieken JH, Marijnen CA (2009) Lymph node retrieval in rectal cancer is dependent on many factors—the role of the tumour, the patient, the surgeon, the radiotherapist and the pathologist. Am J Surg Pathol 33(10):1547–1553PubMedCrossRefGoogle Scholar
  31. 31.
    Kozak KR, Moody JS (2008) The impact of T and N stage on long-term survival of rectal cancer patients in the community. J Surg Oncol 98(3):161–166PubMedCrossRefGoogle Scholar
  32. 32.
    Joseph NE, Sigurdson ER, Hanlon AL et al (2003) Accuracy of determining nodal negativity in colorectal cancer on the basis of the number of nodes retrieved on resection. Ann Surg Oncol 10:213–218PubMedCrossRefGoogle Scholar
  33. 33.
    Goldstein NS, Sanford W, Coffey M, Layfield LJ (1996) Lymph node recovery from colorectal resection specimens removed for adenocarcinoma. Trends over time and a recommendation for a minimum number of lymph nodes to be recovered. Am J Clin Pathol 106:209–216PubMedGoogle Scholar
  34. 34.
    Wong JH, Severino R, Honnebier MG, Tom P, Namiki TS (1999) Number of nodes examined and staging accuracy in colorectal carcinoma. J Clin Oncol 17:2896–2900PubMedGoogle Scholar
  35. 35.
    Berger AC, Watson JC, Ross EA, Hoffman JP (2004) The metastatic/examined lymph node ratio is an important prognostic factor after pancreaticoduodenectomy for pancreatic adenocarcinoma. Am Surg 70:235–240PubMedGoogle Scholar
  36. 36.
    Inoue K, Nakane Y, Iiyama H et al (2002) The superiority of ratio-based lymph node staging in gastric carcinoma. Ann Surg Oncol 9:27–34PubMedCrossRefGoogle Scholar
  37. 37.
    Nitti D, Marchet A, Olivieri M et al (2003) Ratio between metastatic and examined lymph nodes is an independent prognostic factor after D2 resection for gastric cancer: analysis of a large European monoinstitutional experience. Ann Surg Oncol 10:1077–1085PubMedCrossRefGoogle Scholar
  38. 38.
    Noue K, Nakane Y, Iiyama H et al (2002) The superiority of ratio-based lymph node staging in gastric carcinoma. Ann Surg Oncol 9:27–34CrossRefGoogle Scholar
  39. 39.
    Voordeckers M, Vinh-Hung V, Van de Steene J, Lamote J, Storme G (2004) The lymph node ratio as prognostic factor in node-positive breast cancer. Radiother Oncol 70:225–230PubMedCrossRefGoogle Scholar
  40. 40.
    Powell AGMT, W.R., McKee RF, Anderson JH, Going JJ, Edwards J, Horgan PG (2012) The relationship between tumour site, clinicopathological characteristics and cancerspecific survival in patients undergoing surgery for colorectal cancer. Colorectal Dis. 16 epub ahead of printGoogle Scholar
  41. 41.
    Wang H, Wei XZ, Fu CG, Zhao RH, Cao FA (2010) Patterns of lymph node metastasis are different in colon and rectal carcinomas. World J Gastroenterol 16(42):5375–5379PubMedCrossRefGoogle Scholar
  42. 42.
    Kang J, Hur H, Min BS, Lee KY, Kim NK (2011) Prognostic impact of the lymph node ratio in rectal cancer patients who underwent preoperative chemoradiation. J Surg Oncol 104(1):53–58PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • M. Medani
    • 1
  • Niall Kelly
    • 1
  • George Samaha
    • 1
  • G. Duff
    • 1
  • Vourneen Healy
    • 3
  • Elizabeth Mulcahy
    • 3
  • Eoghan Condon
    • 1
  • David Waldron
    • 1
  • Jean Saunders
    • 1
    • 4
  • J. Calvin Coffey
    • 1
    • 2
    • 5
    Email author
  1. 1.Department of General and Colorectal SurgeryUniversity Hospital LimerickLimerickIreland
  2. 2.4i Centre for Interventions in Infection, Inflammation and Immunity, Graduate Entry Medical SchoolUniversity of LimerickLimerickIreland
  3. 3.Department of PathologyUniversity Hospital LimerickLimerickIreland
  4. 4.CSTARUniversity of LimerickLimerickIreland
  5. 5.Department of General Surgery, Graduate Entry Medical SchoolUniversity of LimerickLimerickIreland

Personalised recommendations