Annals of Surgical Oncology

, Volume 18, Issue 13, pp 3743–3754 | Cite as

Nodal Metastasis From Locally Advanced Esophageal Cancer: How Neoadjuvant Therapy Modifies Their Frequency and Distribution

  • Carlo Castoro
  • Marco Scarpa
  • Matteo Cagol
  • Alberto Ruol
  • Francesco Cavallin
  • Rita Alfieri
  • Gianpietro Zanchettin
  • Massimo Rugge
  • Ermanno Ancona
Gastrointestinal Oncology



Neoadjuvant chemoradiotherapy (CT-RT) before esophagectomy seems to affect the number of nodal metastasis and to alter the distribution of those that remain. The aim of this study was to define how neoadjuvant chemoradiotherapy changes nodal metastasis patterns in locally advanced esophageal cancer.


A total of 402 consecutive patients with cancer of the esophagus or esophagogastric junction (181 adenocarcinoma [AC] and 221 squamous cell carcinoma [SCC]) (evaluated at clinical stage T1N1, T2N1, T3N0, or T3N1 and pathological stage M0) presenting in our Department between 1992 and 2007 and who underwent complete resection (R0) were included in this retrospective study on a prospectively collected database. All dissected lymph nodes were retrieved and microscopically analyzed. Nodal metastasis patterns in patients who underwent chemotherapy (CT) or chemoradiotherapy (CT-RT) neoadjuvant therapy were compared with those in patients who underwent surgery alone.


Almost 30% of the adenocarcinoma patients and approximately 40% of the SCC patients showed effective tumor downstaging after neoadjuvant therapy. There were fewer paracardial node metastases (P = .002) in the AC patients who underwent CT-RT neoadjuvant therapy. There were, likewise, significantly fewer paraesophageal, paracardial, and subcarinal node metastases in the SCC patients in whom the perigastric nodes became the second-most frequent site of metastasis.


Not only was frequency of lymph node metastases decreased after neoadjuvant therapy, but nodal localization and pattern were also significantly modified.


Esophageal Cancer Esophageal Squamous Cell Carcinoma Squamous Cell Carcinoma Patient Advanced Esophageal Cancer Middle Thoracic Esophagus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors are extremely grateful to Linda Inverso for her kind help in the revision of the English language and for editing the final version of the paper.


  1. 1.
    Peyre CG, Hagen JA, DeMeester SR, Altorki NK, Ancona E, Griffin SM, et al. The number of lymph nodes removed predicts survival in esophageal cancer: An international study on the impact of extent of surgical resection. Ann Surg. 2008;248: 549–56.PubMedCrossRefGoogle Scholar
  2. 2.
    Altorki N, Skinner D. Should en bloc esophagectomy be the standard of care for esophageal carcinoma? Ann Surg. 2001;234:581–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Hulscher JB, van Sandick JW, de Boer AG, Wijnhoven BP, Tijssen JG, Fockens P, et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med. 2002;347:1662–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Koenig AM, Prenzel KL, Bogoevski D, Yekebas EF, Bubenheim M, Faithova L, et al. Strong impact of micrometastatic tumor cell load in patients with esophageal carcinoma. Ann Surg Oncol. 2008;16:454–62.PubMedCrossRefGoogle Scholar
  5. 5.
    Malaisrie SC, Untch B, Aranha GV, Mohideen N, Hantel A, Pickleman J. Neoadjuvant chemoradiotherapy for locally advanced esophageal cancer Experience at a single institution. Arch Surg. 2004;139:532–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Gebski V, Burmeister B, Smithers BM, Foo K, Zalcberg J, Simes J, et al. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol. 2007;8:226–34.PubMedCrossRefGoogle Scholar
  7. 7.
    Mariette C, Triboulet JP. Is preoperative chemoradiation effective in treatment of oesophageal carcinoma? Lancet Oncol. 2005;6:635–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Mariette C, Piessen G, Lamblin A, Mirabel X, Adenis A, Triboulet JP. Impact of preoperative radiochemotherapy on postoperative course and survival in patients with locally advanced squamous cell oesophageal carcinoma. Br J Surg. 2006;93:1077–83.PubMedCrossRefGoogle Scholar
  9. 9.
    Reynolds JV, Muldoon C, Hollywood D, Ravi N, Rowley S, O’Byrne K, et al. Long-term outcomes following neoadjuvant chemoradiotherapy for esophageal cancer. Ann Surg. 2007;245:707–16.PubMedCrossRefGoogle Scholar
  10. 10.
    Veeramachaneni NK, Zoole JB, Decker PA, Putnam JB, Meyers BF. Lymph node analysis in esophageal resection: American College of Surgeons Oncology Group Z0060 Trial. Ann Thorac Surg. 2008;86:418–21.PubMedCrossRefGoogle Scholar
  11. 11.
    Dresner SM, Lamb PJ, Bennett MK, Hayes N, Griffin SM. The pattern of metastatic lymph node dissemination from adenocarcinoma of the esophagogastric junction. Surgery. 2001;129:103–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Van de Ven C, De Leyn P, Coosemans W, Van Raemdonck D, Lerut T. Three-field lymphadenectomy and pattern of lymph node spread in T3 adenocarcinoma of the distal esophagus and the gastro-esophageal junction. Eur J Cardiothoracic Surg. 1999;15:769–73.PubMedCrossRefGoogle Scholar
  13. 13.
    Akiyama H, Tsurumaru M, Kawamura T, Ono Y. Principles of surgical treatment for carcinoma of the esophagus: analysis of lymph node involvement. Ann Surg. 1981;194:438–46.PubMedCrossRefGoogle Scholar
  14. 14.
    Akiyama H, Tsurumaru M, Udagawa H, Kajiyama J. Radical lymph node dissection for cancer of the thoracic esophagus. Ann Surg. 1994;220:364–72.PubMedCrossRefGoogle Scholar
  15. 15.
    Altorki N, Kent M, Ferrara C, Port J. Three-field lymph nodes dissection for squamous cell and adenocarcinoma of the esophagus. Ann Surg. 2002;236:177–83.PubMedCrossRefGoogle Scholar
  16. 16.
    Lamb PJ, Griffin SM, Burt AD, Lloyd J, Karat D, Hayes N. Sentinel node biopsy to evaluate the metastatic dissemination of oesophageal adenocarcinoma. Br J Surg. 2005;92:60–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Burian M, Stein HJ, Sendler A, Piert M, Nahrig J, Feith M, et al. Sentinel node detection in Barrett’s and cardia cancer. Ann Surg Oncol. 2004;11:255S–8S.PubMedGoogle Scholar
  18. 18.
    Grotenhuis BA, Wijnhoven BPL, van Marion R, van Dekken H, Hop WC, Tilanus HW, et al. The sentinel node concept in adenocarcinomas of the distal esophagus and gastroesophageal junction. J Thorac Cardiovasc Surg. 2009;138:608–12.PubMedCrossRefGoogle Scholar
  19. 19.
    Pennathur A, Awais O, Luketich JD. Technique of minimally invasive Ivor Lewis esophagectomy. Ann Thorac Surg. 2010;89:S2159–62.PubMedCrossRefGoogle Scholar
  20. 20.
    Orringer MB, Marshall B, Chang AC, Lee J, Pickens A, Lau CL. Two thousand transhiatal esophagectomies: changing trends, lessons learned. Ann Surg. 2007;246:363–72; discussion 372–4.PubMedCrossRefGoogle Scholar
  21. 21.
    Sobin L, Wittekind C. UICC: TNM Classification of Malignant Tumors. 6th ed. New York: Wiley, 2002.Google Scholar
  22. 22.
    Ruol A, Portale G, Castoro C, Merigliano S, Cavallin F, Battaglia G, et al. Management of esophageal cancer in patients aged over 80 years. Eur J Cardiothorac Surg. 2007;32:445–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Cagol M, Ruol A, Castoro C, Alfieri R, Michieletto S, Ancona E. Prophylactic thoracic duct mass ligation prevents chylothorax after transthoracic esophagectomy for cancer. World J Surg. 2009;33:1684–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Holscher A, Schroder W, Bollschweiler E, Beckurts K, Schneider P. How safe is high intrathoracic esophagogastrostomy? Chirurgie. 2003;74:726–33.CrossRefGoogle Scholar
  25. 25.
    Ancona E, Ruol A, Santi S, Merigliano S, Sileni VC, Koussis H, et al. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone. Cancer. 2001;91: 2165–74.PubMedCrossRefGoogle Scholar
  26. 26.
    Barbour AP, Jones M, Gonen M, Gotley DC, Thomas J, Thomson DB, et al. Refining esophageal cancer staging after neoadjuvant therapy: importance of treatment response. Ann Surg Oncol. 2008;15:2894–902.PubMedCrossRefGoogle Scholar
  27. 27.
    Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, et al. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998;339:1979–84.PubMedCrossRefGoogle Scholar
  28. 28.
    Law S, Fok M, Chow S, Chu K, Wong J. Preoperative chemotherapy versus surgical therapy alone for squamous cell carcinoma of the esophagus: a prospective randomized trial. J Thorac Cardiovasc Surg. 1997;114:210–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Forastiere AA, Heitmiller RF, Kleinberg L. Multimodality therapy for esophageal cancer. Chest. 1997;112(suppl):195S–200S.PubMedCrossRefGoogle Scholar
  30. 30.
    Lehnert T. Multimodal therapy for squamous carcinoma of the oesophagus. Br J Surg. 1999;86:727–39.PubMedCrossRefGoogle Scholar
  31. 31.
    Sutton P, Clark P. Neo-adjuvant treatment for oesophageal cancer. GI Cancer. 2000;3:231–8.Google Scholar
  32. 32.
    Geh JI, Crellin AM, Glynne-Jones R. Preoperative (neoadjuvant) chemoradiotherapy in oesophageal cancer. Br J Surg. 2001;88:338–56.PubMedCrossRefGoogle Scholar
  33. 33.
    Fumagalli U. Resective surgery for cancer of the thoracic esophagus: results of a consensus conference held at the VIth World Congress of the International Society for Diseases of the Esophagus. Dis Esophagus. 1996;9:S30–S38.Google Scholar
  34. 34.
    Lagarde SM, Reitsma JB, ten Kate FJW, Busch ORC, Obertop H, Zwinderman AH, et al. Predicting individual survival after potentially curative esophagectomy for adenocarcinoma of the esophagus or gastroesophageal junction. Ann Surg. 2008;248:1006–13.PubMedCrossRefGoogle Scholar
  35. 35.
    Kato H, Tachimori Y, Watanabe H, Iizuka T, Terui S, Itabashi M, et al. Lymph nodes metastasis in thoracic esophageal carcinoma. J Surg Oncol. 1991;48:106–11.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2011

Authors and Affiliations

  • Carlo Castoro
    • 1
  • Marco Scarpa
    • 1
  • Matteo Cagol
    • 1
  • Alberto Ruol
    • 2
  • Francesco Cavallin
    • 1
  • Rita Alfieri
    • 1
  • Gianpietro Zanchettin
    • 2
  • Massimo Rugge
    • 3
  • Ermanno Ancona
    • 1
    • 2
  1. 1.Oncological Surgery UnitVeneto Institute of Oncology (IOV-IRCCS)PadovaItaly
  2. 2.Department of Surgical and Gastroenterological SciencesUniversity of PadovaPadovaItaly
  3. 3.Department of PathologyUniversity of PadovaPadovaItaly

Personalised recommendations