Annals of Surgical Oncology

, Volume 22, Supplement 3, pp 580–587 | Cite as

Impact of Total Lymph Node Count on Staging and Survival After Neoadjuvant Chemoradiation Therapy for Rectal Cancer

  • Matthew D. Hall
  • Timothy E. Schultheiss
  • David D. Smith
  • Marwan G. Fakih
  • Joseph Kim
  • Jeffrey Y. C. Wong
  • Yi-Jen Chen
Colorectal Cancer

Abstract

Purpose

Current guidelines recommend that a minimum of 12 lymph nodes (LNs) be dissected to accurately stage rectal cancer patients. Neoadjuvant chemoradiation therapy (CRT) decreases the number of LNs retrieved at surgery. The purpose of this study was to assess the impact of the number of LNs dissected on overall survival (OS) for localized rectal cancer patients treated with neoadjuvant CRT.

Methods

Treatment data were obtained on all patients treated for rectal cancer (2000–2013) in the National Oncology Data Alliance™, a proprietary database of merged tumor registries. Eligible patients were treated with neoadjuvant CRT followed by surgery and had complete data on number of positive LNs, number of LNs examined, and treatment dates (n = 4565).

Results

Hazard ratios for OS decreased sequentially with increasing number of LNs examined until a maximum benefit was achieved with examination of eight LNs. On multivariate analysis, age, sex, race, marital status, grade, ypT stage, ypN stage, type of surgery, margin status, presence of pathologically confirmed metastasis at surgery, and number of LNs examined were significant predictors of OS.

Conclusions

Examination of eight or more LNs in rectal cancer patients treated with neoadjuvant CRT resulted in accurate staging and assignment into prognostic groups with an ensuing improvement in OS by stage. This study suggests that eight LNs is the threshold for an adequate lymph node dissection after neoadjuvant CRT.

Keywords

Overall Survival Rectal Cancer Total Mesorectal Excision National Comprehensive Cancer Network Rectal Cancer Patient 

Notes

Disclosure

None.

References

  1. 1.
    Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351(17):1731–40.PubMedCrossRefGoogle Scholar
  2. 2.
    Peeters KC, Marijnen CA, Nagtegaal ID, et al. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg. 2007;246(5):693–701.PubMedCrossRefGoogle Scholar
  3. 3.
    Ortholan C, Francois E, Thomas O, Benchimol D, Baulieux J, Bosset JF, et al. Role of radiotherapy with surgery for T3 and resectable T4 rectal cancer: evidence from randomized trials. Dis Colon Rectum. 2006;49(3):302–10.PubMedCrossRefGoogle Scholar
  4. 4.
    Kim DW, Lim SB, Kim DY, et al. Pre-operative chemo-radiotherapy improves the sphincter preservation rate in patients with rectal cancer located within 3 cm of the anal verge. Eur J Surg Oncol. 2006;32(2):162–7.PubMedCrossRefGoogle Scholar
  5. 5.
    National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: rectal cancer. 2013. http://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf. Accessed 31 Dec 2014.
  6. 6.
    Compton CC, Fielding LP, Burgart LJ, et al. Prognostic factors in colorectal cancer: College of American Pathologists consensus statement 1999. Arch Pathol Lab Med. 2000;124(7):979–94.PubMedGoogle Scholar
  7. 7.
    Nelson H, Petrelli N, Carlin A, et al. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst. 2001;93(8):583–96.PubMedCrossRefGoogle Scholar
  8. 8.
    Gunderson LL, Jessup JM, Sargent DJ, Greene FL, Stewart A. Revised tumor and node categorization for rectal cancer based on Surveillance, Epidemiology, and End Results and rectal pooled analysis outcomes. J Clin Oncol. 2010;28(2):256–63.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Tepper JE, O’Connell MJ, Niedzwiecki D, et al. Impact of number of nodes retrieved on outcome in patients with rectal cancer. J Clin Oncol. 2001;19:157–63.PubMedGoogle Scholar
  10. 10.
    Le M, Nelson R, Lee W, et al. Evaluation of lymphadenectomy in patients receiving neoadjuvant radiotherapy for rectal adenocarcinoma. Ann Surg Oncol. 2012;19:3713–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Scabini S, Montecucco F, Nencioni A, et al. The effect of preoperative chemoradiotherapy on lymph nodes harvested in TME for rectal cancer. World J Surg Oncol. 2013;11:292.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Govindarajan A, Gönen M, Weiser MR, et al. Challenging the feasibility and clinical significance of current guidelines on lymph node examination in rectal cancer in the era of neoadjuvant therapy. J Clin Oncol. 2011;29(34):4568–73.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Miller ED, Robb BW, Cummings OW, Johnstone PA. The effects of preoperative chemoradiotherapy on lymph node sampling in rectal cancer. Dis Colon Rectum. 2012;55(9):1002–7.PubMedCrossRefGoogle Scholar
  14. 14.
    National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov). SEER*Stat Database: Incidence – SEER 18 Regs Research Data, Nov 2012 Sub (1973-2010) < Katrina/Rita Population Adjustment >—Linked To County Attributes—Total U.S., 1973-2012 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released September 2013.
  15. 15.
    Harrell FE Jr (2014) Regression modeling strategies with applications to linear models, logistic regression, and survival analysis. Springer, New York pp 13–15; 509–522Google Scholar
  16. 16.
    Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. (eds). (2009) AJCC Cancer Staging Manual. 7th ed. Springer, New York pp 144–166Google Scholar
  17. 17.
    Wichmann MW, Müller C, Meyer G, et al. Effect of preoperative radiochemotherapy on lymph node retrieval after resection of rectal cancer. Arch Surg. 2002;137(2):206–10.PubMedCrossRefGoogle Scholar
  18. 18.
    Baxter NN, Morris AM, Rothenberger DA, Tepper JE. Impact of preoperative radiation for rectal cancer on subsequent lymph node evaluation: a population-based analysis. Int J Radiat Oncol Biol Phys. 2005;61(2):426–31.PubMedCrossRefGoogle Scholar
  19. 19.
    Ha YH, Jeong SY, Lim SB, et al. Influence of preoperative chemoradiotherapy on the number of lymph nodes retrieved in rectal cancer. Ann Surg. 2010;252(2):336–40.PubMedCrossRefGoogle Scholar
  20. 20.
    Lykke J, Roikjær O, Jess P, et al. Tumour stage and preoperative chemoradiotherapy influence the lymph node yield in stages I-III rectal cancer: results from a prospective nationwide cohort study. Colorectal Dis. 2014;16(4):144–9.CrossRefGoogle Scholar
  21. 21.
    Mekenkamp LJ, van Krieken JH, Marijnen CA, et al. Lymph node retrieval in rectal cancer is dependent on many factors: the role of the tumor, the patient, the surgeon, the radiotherapist, and the pathologist. Am J Surg Pathol. 2009;33(10):1547–53.PubMedCrossRefGoogle Scholar
  22. 22.
    Morris EJ, Maughan NJ, Forman D, Quirke P. Identifying stage III colorectal cancer patients: the influence of the patient, surgeon, and pathologist. J Clin Oncol. 2007;25(18):2573–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Thompson RH, Carver BS, Bosl GJ, et al. Body mass index is associated with higher lymph node counts during retroperitoneal lymph node dissection. Urology. 2012;79(2):361–4.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    van Gijn W, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicenter, randomised controlled TME trial. Lancet Oncol. 2011;12(6):575–82.PubMedCrossRefGoogle Scholar
  25. 25.
    Kapiteijn E, Kranenbarg EK, Steup WH, et al. Total mesorectal excision (TME) with or without preoperative radiotherapy in the treatment of primary rectal cancer: prospective randomised trial with standard operative and histopathological techniques. Eur J Surg. 1999;165(5):410–20.PubMedCrossRefGoogle Scholar
  26. 26.
    Demetter P, Vandendael T, Sempoux C, et al. Need for objective and reproducible criteria in histopathological assessment of total mesorectal excision specimens: lessons from a national improvement project. Colorectal Dis. 2013;15(11):1351–8.PubMedCrossRefGoogle Scholar
  27. 27.
    La Torre M, Mazzuca F, Ferri M, et al. The importance of lymph node retrieval and lymph node ratio following preoperative chemoradiation of rectal cancer. Colorectal Dis. 2013;15(7):e382–8.PubMedCrossRefGoogle Scholar
  28. 28.
    de Campos-Lobato LF, Stocchi L, de Sousa JB, et al. Less than 12 nodes in the surgical specimen after total mesorectal excision following neoadjuvant chemoradiation: it means more than you think! Ann Surg Oncol. 2013;20(11):3398–406.PubMedCrossRefGoogle Scholar
  29. 29.
    Persiani R, Biondi A, Gambacorta MA, et al. Prognostic implications of the lymph node count after neoadjuvant treatment for rectal cancer. Br J Surg. 2014;101(2):133–42.PubMedCrossRefGoogle Scholar
  30. 30.
    Smith DD, Schwarz RR, Schwarz RE. 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. 2005;23(28):7114–24.PubMedCrossRefGoogle Scholar
  31. 31.
    Marchet A, Mocellin S, Ambrosi A, et al. The prognostic value of N-ratio in patients with gastric cancer: validation in a large, multicenter series. Eur J Surg Oncol. 2008;34(2):159–65.PubMedCrossRefGoogle Scholar
  32. 32.
    Wang J, Dang P, Raut CP, et al. Comparison of a lymph node ratio-based staging system with the 7th AJCC system for gastric cancer: analysis of 18,043 patients from the SEER database. Ann Surg. 2012;255(3):478–85.PubMedCrossRefGoogle Scholar
  33. 33.
    Wang J, Hassett JM, Dayton MT, Kulaylat MN. The prognostic superiority of log odds of positive lymph nodes in stage III colon cancer. J Gastrointest Surg. 2008;12(10):1790–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Smith DD, Nelson RA, Schwarz RE. A comparison of five competing lymph node staging schemes in a cohort of resectable gastric cancer patients. Ann Surg Oncol. 2014;21(3):875–82.PubMedCrossRefGoogle Scholar
  35. 35.
    Marks JH, Valsdottir EB, Rather AA, Nweze IC, Newman DA, Chernick MR. Fewer than 12 lymph nodes can be expected in a surgical specimen after high-dose chemoradiation therapy for rectal cancer. Dis Colon Rectum. 2010;53(7):1023–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Lee W, Nelson R, Akmal Y, et al. Racial and ethnic disparities in outcomes with radiation therapy for rectal adenocarcinoma. Int J Colorectal Dis. 2012;27(6):737–49.PubMedCrossRefGoogle Scholar
  37. 37.
    Kim J, Sun CL, Mailey B, et al. Race and ethnicity correlate with survival in patients with gastric adenocarcinoma. Ann Oncol. 2010;21(1):152–60.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • Matthew D. Hall
    • 1
  • Timothy E. Schultheiss
    • 1
  • David D. Smith
    • 2
  • Marwan G. Fakih
    • 3
  • Joseph Kim
    • 4
  • Jeffrey Y. C. Wong
    • 1
  • Yi-Jen Chen
    • 1
  1. 1.Department of Radiation OncologyCity of Hope National Medical CancerDuarteUSA
  2. 2.Division of BiostatisticsCity of Hope National Medical CancerDuarteUSA
  3. 3.Department of Medical Oncology and Therapeutics ResearchCity of Hope National Medical CancerDuarteUSA
  4. 4.Department of SurgeryCity of Hope National Medical CancerDuarteUSA

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