Harvest of at least 18 lymph nodes is associated with improved survival in patients with pN0 colon cancer: a retrospective cohort study



To investigate the correlation between number of retrieved lymph nodes (rLNs) and prognosis and further ascertain the optimal number of rLNs with a beneficial survival impact in patients with pN0 colon cancer.


The Surveillance, Epidemiology, and End Results (SEER) database was searched for pN0 colon cancer cases. X-Tile software and Kaplan–Meier survival analysis were applied to determine the optimal number of rLNs based on the minimal probability (P) value and the largest χ2 value. Univariate analyses and Cox proportional hazard regression model were used to investigate the relationship between rLN number and overall survival. Multiple analyses were conducted to assess the prognostic predictive ability of the identified optimal rLN cut-off value under different stratifications. Nomograms were established based on the independent prognostic factors selected by the multivariate analysis to predict 3- and 5-year overall survival rates of pN0 patients.


A total of 6269 pN0 colon cancer patients who underwent surgical therapy were finally included for analysis. Harvest of at least 18 lymph nodes was determined as the optimal rLN number. This cut-off rLN value (< 18 versus ≥ 18) was identified as an independent prognostic factor (P < 0.001) of overall survival via multivariate analysis. Similar findings were obtained in patients with retrieval of at least 12 lymph nodes (18 > rLNs ≥ 12 versus rLNs ≥ 18) stratified into several groups.


The number of rLNs was identified as an independent prognostic factor for pN0 colon cancer. Retrieval of at least 18 lymph nodes was associated with favorable prognosis in patients with pN0 colon cancer, and should, therefore, be regarded as an alternative cut-off value for survival analysis.

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Data availability

The data sets used and/or analyzed during the current study are available from the SEER database.



American Joint Committee on Cancer


Confidence interval


Hazard ratio

pT stage:

Pathological T stage

pN stage:

Pathological N stage




Retrieved lymph nodes


Surveillance, Epidemiology, and End Results




Union for International Cancer Control


  1. Agha R, Abdall-Razak A, Crossley E, Dowlut N, Iosifidis C, Mathew G, STROCSS Group (2019) The STROCSS 2019 guideline: strengthening the reporting of cohort studies in surgery. Int J Surg 72:156–165. https://doi.org/10.1016/j.ijsu.2019.11.002

    Article  PubMed  Google Scholar 

  2. Amin MB, Edge SB (2017) AJCC cancer staging manual, 8th edn. Springer, New York

    Google Scholar 

  3. Amin MB, Greene FL, Edge SB et al (2017) The eighth editions AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin 67:93–99. https://doi.org/10.3322/caac.21388

    Article  PubMed  Google Scholar 

  4. Baxter NN, Virnig DJ, Rothenberger DA, Morris AM, Jessurun J, Virnig BA (2005) Lymph node evaluation in colorectal cancer patients: a population-based study. J Natl Cancer Inst 97:219–225. https://doi.org/10.1093/jnci/dji020

    Article  PubMed  Google Scholar 

  5. Baxter NN, Ricciardi R, Simunovic M, Urbach DR, Virnig BA (2010) An evaluation of the relationship between lymph node number and staging in pT3 colon cancer using population-based data. Dis Colon Rectum 53:65–70. https://doi.org/10.1007/DCR.0b013e3181c70425

    Article  PubMed  Google Scholar 

  6. Brierley JD, Gospodarowicz MK, Wittekind C (2017) The TNM classification of malignant tumours, 8th edn. Wiley Blackwell, Oxford

    Google Scholar 

  7. Camp RL, Dolled-Filhart M, Rimm DL (2004) X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res 10:7252–7259. https://doi.org/10.1158/1078-0432.CCR-04-0713

    CAS  Article  PubMed  Google Scholar 

  8. Caplin S, Cerottini JP, Bosman FT, Constanda MT, Givel JC (1998) For patients with Dukes' B (TNM Stage II) colorectal carcinoma, examination of six or fewer lymph nodes is related to poor prognosis. Cancer 83:666–672. https://doi.org/10.1002/(sici)1097-0142(19980815)83:4%3c666:aid-cncr6%3e3.0.co;2-i

    CAS  Article  PubMed  Google Scholar 

  9. Chau I, Cunningham D (2002) Adjuvant therapy in colon cancer: current status and future directions. Cancer Treat Rev 28:223–236. https://doi.org/10.1016/s0305-7372(02)00047-6

    CAS  Article  PubMed  Google Scholar 

  10. Chen SL, Bilchik AJ (2006) More extensive nodal dissection improves survival for stages I to III of colon cancer: a population-based study. Ann Surg 244:602–610. https://doi.org/10.1097/01.sla.0000237655.11717.50

    Article  PubMed  PubMed Central  Google Scholar 

  11. Chen SL, Steele SR, Eberhardt J, Zhu K, Bilchik A, Stojadinovic A (2011) Lymph node ratio as a quality and prognostic indicator in stage III colon cancer. Ann Surg 253:82–87. https://doi.org/10.1097/SLA.0b013e3181ffa780

    Article  PubMed  Google Scholar 

  12. Compton C, Fenoglio-Preiser CM, Pettigrew N (2000) American Joint Committee on Cancer Prognostic Factors Consensus Conference: Colorectal Working Group. Cancer 88:1739–1757. https://doi.org/10.1002/(sici)1097-0142(20000401)88:7%3c1739:aid-cncr30%3e3.0.co;2-t

    CAS  Article  PubMed  Google Scholar 

  13. Evans MD, Barton K, Rees A, Stamatakis JD, Karandikar SS (2008) The impact of surgeon and pathologist on lymph node retrieval in colorectal cancer and its impact on survival for patients with Dukes' stage B disease. Colorectal Dis 10:157–164. https://doi.org/10.1111/j.1463-1318.2007.01225.x

    CAS  Article  PubMed  Google Scholar 

  14. Gajra A, Newman N, Gamble GP, Kohman LJ, Graziano SL (2003) Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer. J Clin Oncol 21:1029–1034. https://doi.org/10.1200/JCO.2003.07.010

    Article  PubMed  Google Scholar 

  15. Goldstein NS (2002) Lymph node recoveries from 2427 pT3 colorectal resection specimens spanning 45 years: recommendations for a minimum number of recovered lymph nodes based on predictive probabilities. Am J Surg Pathol 26:179–189. https://doi.org/10.1097/00000478-200202000-00004

    Article  PubMed  Google Scholar 

  16. Hayashi S, Kanda M, Ito S et al (2019) Number of retrieved lymph nodes is an independent prognostic factor after total gastrectomy for patients with stage III gastric cancer: propensity score matching analysis of a multi-institutiondataset. Gastric Cancer 22:853–863. https://doi.org/10.1007/s10120-018-0902-2

    Article  PubMed  Google Scholar 

  17. He WZ, Xie QK, Hu WM, Kong PF, Yang L, Yang YZ, Jiang C (2018) An increased number of negative lymph nodes is associated with a higher immune response and longer survival in colon cancer patients. Cancer Manag Res 10:1597–1604. https://doi.org/10.2147/CMAR.S160100

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. Herr HW, Bochner BH, Dalbagni G, Donat SM, Reuter VE, Bajorin DF (2002) Impact of the number of lymph nodes retrieved on outcome in patients with muscle invasive bladder cancer. J Urol 167:1295–1298. https://doi.org/10.1016/s0022-5347(05)65284-6

    Article  PubMed  Google Scholar 

  19. Jestin P, Påhlman L, Glimelius B, Gunnarsson U (2005) Cancer staging and survival in colon cancer is dependent on the quality of the pathologists’ specimen examination. Eur J Cancer 41:2071–2078. https://doi.org/10.1016/j.ejca.2005.06.012

    CAS  Article  PubMed  Google Scholar 

  20. Johnson PM, Malatjalian D, Porter GA (2002) Adequacy of nodal harvest in colorectal cancer: a consecutive cohort study. J Gastrointest Surg 6:883–888. https://doi.org/10.1016/s1091-255x(02)00131-2

    Article  PubMed  Google Scholar 

  21. 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 10:213–218. https://doi.org/10.1245/aso.2003.03.059

    Article  PubMed  Google Scholar 

  22. Law CH, Wright FC, Rapanos T, Alzahrani M, Hanna SS, Khalifa M, Smith AJ (2003) Impact of lymph node retrieval and pathological ultra-staging on the prognosis of stage II colon cancer. J Surg Oncol 84:120–126. https://doi.org/10.1002/jso.10309

    Article  PubMed  Google Scholar 

  23. Le Voyer TE, Sigurdson ER, Hanlon AL, Mayer RJ, Macdonald JS, Catalano PJ, Haller DG (2003) Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT-0089. J Clin Oncol 21:2912–2919. https://doi.org/10.1200/JCO.2003.05.062

    Article  PubMed  Google Scholar 

  24. National Cancer Institute (2018) Surveillance, epidemiology, and end results (SEER) program, research data (1973–2015). National Cancer Institute: Bethesda, MD, USA. www.seer.cancer.gov. Accessed 19 Feb 2019

  25. O'Sullivan B, Brierley J, Byrd D et al (2017) The TNM classification of malignant tumours-towards common understanding and reasonable expectations. Lancet Oncol 18:849–851. https://doi.org/10.1016/S1470-2045(17)30438-2

    Article  PubMed  PubMed Central  Google Scholar 

  26. Pan S, Wang P, Xing Y, Li K, Wang Z, Xu H, Zhu Z (2019) Retrieved lymph nodes from different anatomic groups in gastric cancer: a proposed optimal number, comparison with other nodal classification strategies and its impact on prognosis. Cancer Commun (Lond) 39:49. https://doi.org/10.1186/s40880-019-0394-4

    CAS  Article  Google Scholar 

  27. Parsons HM, Tuttle TM, Kuntz KM, Begun JW, McGovern PM, Virnig BA (2011) Association between lymph node evaluation for colon cancer and node positivity over the past 20 years. JAMA 306:1089–1097. https://doi.org/10.1001/jama.2011.1285

    CAS  Article  PubMed  Google Scholar 

  28. Pinato DJ, Howlett S, Ottaviani D et al (2019) Association of prior antibiotic treatment with survival and response to immune checkpoint inhibitor therapy in patients with cancer. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2019.2785

    Article  PubMed  Google Scholar 

  29. Quan Q, Zhu M, Liu S et al (2019) Positive impact of the negative lymph node count on the survival rate of stage III colon cancer with pN1 and right-side disease. J Cancer 10:1052–1059. https://doi.org/10.7150/jca.23763

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. Sarli L, Bader G, Iusco D et al (2005) Number of lymph nodes examined and prognosis of TNM stage II colorectal cancer. Eur J Cancer 41:272–279. https://doi.org/10.1016/j.ejca.2004.10.010

    Article  PubMed  Google Scholar 

  31. Shanmugam C, Hines RB, Jhala NC et al (2011) Evaluation of lymph node numbers for adequate staging of Stage II and III colon cancer. J Hematol Oncol 4:25. https://doi.org/10.1186/1756-8722-4-25

    Article  PubMed  PubMed Central  Google Scholar 

  32. Siegel RL, Miller KD, Jemal AR (2019) Cancer statistics, 2019. CA Cancer J Clin 69:7–34. https://doi.org/10.3322/caac.21551

    Article  PubMed  Google Scholar 

  33. Smith DD, Schwarz RR, Schwarz RE (2005) Impact of total lymph node count on staging and survival after gastrectomy for gastric cancer: data from a large US-population database. J Clin Oncol 23:7114–7124. https://doi.org/10.1200/JCO.2005.14.621

    Article  PubMed  Google Scholar 

  34. Swanson RS, Compton CC, Stewart AK, Bland KI (2003) The prognosis of T3N0 colon cancer is dependent on the number of lymph nodes examined. Ann Surg Oncol 10:65–71. https://doi.org/10.1245/aso.2003.03.058

    Article  PubMed  Google Scholar 

  35. Tepper JE, O'Connell MJ, Niedzwiecki D et al (2001) Impact of number of nodes retrieved on outcome in patients with rectal cancer. J Clin Oncol 19:157–163. https://doi.org/10.1200/JCO.2001.19.1.157

    CAS  Article  PubMed  Google Scholar 

  36. Wong SL, Ji H, Hollenbeck BK, Morris AM, Baser O, Birkmeyer JD (2007) Hospital lymph node examination rates and survival after resection for colon cancer. JAMA 298:2149–2154. https://doi.org/10.1001/jama.298.18.2149

    CAS  Article  PubMed  Google Scholar 

  37. Wright FC, Law CH, Last L et al (2003) Lymph node retrieval and assessment in stage II colorectal cancer: a population-based study. Ann Surg Oncol 10:903–909. https://doi.org/10.1245/aso.2003.01.012

    CAS  Article  PubMed  Google Scholar 

  38. Wright FC, Gagliardi AR, Law CH et al (2008) A randomized controlled trial to improve lymph node assessment in stage II colon cancer. Arch Surg 143:1050–1055. https://doi.org/10.1001/archsurg.143.11.1050

    Article  PubMed  Google Scholar 

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We acknowledgment the efforts of Surveillance, Epidemiology and End Results (SEER) program tumor registries for creating SEER database (https://seer.cancer.gov/). We thank International Science Editing for their professional editing.


This work was supported, in part, by the China Scholarship Council (201908050148), Japan China Sasakawa Medical Fellowship (2017816), and National Natural Science Foundation of China (81774112).

Author information




Study concept and design: FN, JP, NZ, and CZ. Acquisition of data: FN, JP, NZ, and CZ. Analysis and interpretation of data: FN, JP, NZ, XZ, ZM, and CZ. Drafting of the manuscript: FN and CZ. Critical revision of the manuscript for important intellectual content: FN, JP, NZ, JW, HQ, XZ, ZM, KN, MA, and CZ. Obtained funding: CZ and ZM. Corresponding author: C.Z.

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Correspondence to Chun-Dong Zhang.

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Ning, F., Pei, J., Zhang, N. et al. Harvest of at least 18 lymph nodes is associated with improved survival in patients with pN0 colon cancer: a retrospective cohort study. J Cancer Res Clin Oncol 146, 2117–2133 (2020). https://doi.org/10.1007/s00432-020-03212-y

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  • Colon cancer
  • pN0 patients
  • Retrieved lymph nodes
  • SEER