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Diagnosis and staging of esophageal cancer

John R Saltzman, MD, FACP, FACG, FASGE, AGAF
Michael K Gibson, MD, PhD, FACP
Section Editors
Douglas A Howell, MD, FASGE, FACG
Richard M Goldberg, MD
Deputy Editor
Diane MF Savarese, MD


Squamous cell carcinoma (SCC) and adenocarcinoma account for over 95 percent of esophageal malignant tumors. For most of the twentieth century, SCC has predominated. In the 1960s, SCC accounted for more than 90 percent of all esophageal tumors in the United States, and adenocarcinomas were considered so uncommon that some authorities questioned their existence. For the past two decades, however, the incidence of esophageal adenocarcinoma has increased dramatically in Western countries, such that the adenocarcinoma now accounts for >60 percent of all esophageal cancers in the United States. In contrast, worldwide, squamous cell cancer still predominates [1]. (See "Epidemiology, pathobiology, and clinical manifestations of esophageal cancer".)

Esophageal SCC and adenocarcinomas differ in a number of features, including tumor location and predisposing factors (table 1). Smoking and alcohol are major risk factors for SCC while Barrett's esophagus with specialized intestinal metaplasia (a complication of gastroesophageal reflux disease [GERD]), obesity, smoking, and possibly GERD itself are the risk factors for adenocarcinoma [2]. (See "Epidemiology, pathobiology, and clinical manifestations of esophageal cancer".)

There seems little doubt that esophageal SCCs and adenocarcinomas represent two different diseases with characteristic pathogenesis, epidemiology, tumor biology, and outcomes. In acknowledgement of these differences, the current 2010 tumor, node, metastasis (TNM) staging system provides separate stage groupings (but similar definitions for tumor, nodal, and metastasis categories) for SCCs and adenocarcinomas of the esophagus and esophagogastric junction (table 2 and table 3) [3]. The newest TNM staging classification (eighth edition, 2017), which is scheduled to go into effect in the United States on January 1, 2018, has further refined these histology-specific prognostic stage groupings (table 4) [4]. Outside of the United States, the Union for International Cancer Control (UICC) has implemented the eighth edition changes as of January 1, 2017. (See 'TNM staging criteria' below.)

In clinical practice, however, there is controversy as to whether and how histology should influence the therapeutic approach. This issue is addressed elsewhere. (See "Radiation therapy, chemoradiotherapy, neoadjuvant approaches, and postoperative adjuvant therapy for localized cancers of the esophagus", section on 'Squamous cell versus adenocarcinoma'.)

Regardless of histology, approximately 50 to 60 percent of patients with esophageal cancer present with incurable locally advanced or metastatic disease. Prolonged progression-free survival is possible in only a few of such patients while palliation is the goal of treatment for the majority. (See "Management of locally advanced unresectable and inoperable esophageal cancer" and "Systemic therapy for locally advanced unresectable and metastatic esophageal and gastric cancer".)


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Literature review current through: Jan 2017. | This topic last updated: Thu Feb 16 00:00:00 GMT 2017.
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  1. Baquet CR, Commiskey P, Mack K, et al. Esophageal cancer epidemiology in blacks and whites: racial and gender disparities in incidence, mortality, survival rates and histology. J Natl Med Assoc 2005; 97:1471.
  2. Engel LS, Chow WH, Vaughan TL, et al. Population attributable risks of esophageal and gastric cancers. J Natl Cancer Inst 2003; 95:1404.
  3. American Joint Committee on Cancer Staging Manual, 7th, Edge SB, Byrd DR, Compton CC, et al (Eds), Springer, New York 2010. p.103.
  4. Rice TW, Kelsen D, Blackstone EH, et al.. Esophagus and esophagogastric junction.. In: AJCC Cancer Staging Manual, 8th, Amin MB. (Ed), AJCC, Chicago 2017. p.185.
  5. Lightdale CJ. Esophageal cancer. American College of Gastroenterology. Am J Gastroenterol 1999; 94:20.
  6. Yendamuri S, Swisher SG, Correa AM, et al. Esophageal tumor length is independently associated with long-term survival. Cancer 2009; 115:508.
  7. Graham DY, Schwartz JT, Cain GD, Gyorkey F. Prospective evaluation of biopsy number in the diagnosis of esophageal and gastric carcinoma. Gastroenterology 1982; 82:228.
  8. Acosta MM, Boyce HW Jr. Chromoendoscopy--where is it useful? J Clin Gastroenterol 1998; 27:13.
  9. Rice TW, Rusch VW, Ishwaran H, et al. Cancer of the esophagus and esophagogastric junction: data-driven staging for the seventh edition of the American Joint Committee on Cancer/International Union Against Cancer Cancer Staging Manuals. Cancer 2010; 116:3763.
  10. Rüdiger Siewert J, Feith M, Werner M, Stein HJ. Adenocarcinoma of the esophagogastric junction: results of surgical therapy based on anatomical/topographic classification in 1,002 consecutive patients. Ann Surg 2000; 232:353.
  11. Ajani JA, In H, Sano T, et al.. Stomach.. In: AJCC Cancer Staging Manual, 8th, Amin MB.. (Ed), AJCC, Chicago 2017. p.203.
  12. Rizk NP, Venkatraman E, Bains MS, et al. American Joint Committee on Cancer staging system does not accurately predict survival in patients receiving multimodality therapy for esophageal adenocarcinoma. J Clin Oncol 2007; 25:507.
  13. Barbour AP, Jones M, Gonen M, et al. Refining esophageal cancer staging after neoadjuvant therapy: importance of treatment response. Ann Surg Oncol 2008; 15:2894.
  14. Nomura M, Shitara K, Kodaira T, et al. Prognostic impact of the 6th and 7th American Joint Committee on Cancer TNM staging systems on esophageal cancer patients treated with chemoradiotherapy. Int J Radiat Oncol Biol Phys 2012; 82:946.
  15. Rice TW, Apperson-Hansen C, DiPaola LM, et al. Worldwide Esophageal Cancer Collaboration: clinical staging data. Dis Esophagus 2016; 29:707.
  16. Rice TW, Lerut TE, Orringer MB, et al. Worldwide Esophageal Cancer Collaboration: neoadjuvant pathologic staging data. Dis Esophagus 2016; 29:715.
  17. Rice TW, Chen LQ, Hofstetter WL, et al. Worldwide Esophageal Cancer Collaboration: pathologic staging data. Dis Esophagus 2016; 29:724.
  18. Rice TW, Ishwaran H, Kelsen DP, et al. Recommendations for neoadjuvant pathologic staging (ypTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals. Dis Esophagus 2016; 29:906.
  19. Rice TW, Ishwaran H, Blackstone EH, et al. Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals. Dis Esophagus 2016; 29:913.
  20. Rice TW, Ishwaran H, Hofstetter WL, et al. Recommendations for pathologic staging (pTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals. Dis Esophagus 2016; 29:897.
  21. American Joint Committee on Cancer Staging Manual, 6th, Greene FL, Page DL, Fleming ID, et al (Eds), Springer-Verlag, New York 2002. p.91.
  22. Chirieac LR, Swisher SG, Ajani JA, et al. Posttherapy pathologic stage predicts survival in patients with esophageal carcinoma receiving preoperative chemoradiation. Cancer 2005; 103:1347.
  23. Rohatgi P, Swisher SG, Correa AM, et al. Characterization of pathologic complete response after preoperative chemoradiotherapy in carcinoma of the esophagus and outcome after pathologic complete response. Cancer 2005; 104:2365.
  24. Lin CS, Chang SC, Wei YH, et al. Prognostic variables in thoracic esophageal squamous cell carcinoma. Ann Thorac Surg 2009; 87:1056.
  25. Peyre CG, Hagen JA, DeMeester SR, et al. Predicting systemic disease in patients with esophageal cancer after esophagectomy: a multinational study on the significance of the number of involved lymph nodes. Ann Surg 2008; 248:979.
  26. Zhang HL, Chen LQ, Liu RL, et al. The number of lymph node metastases influences survival and International Union Against Cancer tumor-node-metastasis classification for esophageal squamous cell carcinoma. Dis Esophagus 2010; 23:53.
  27. Rizk N, Venkatraman E, Park B, et al. The prognostic importance of the number of involved lymph nodes in esophageal cancer: implications for revisions of the American Joint Committee on Cancer staging system. J Thorac Cardiovasc Surg 2006; 132:1374.
  28. Mariette C, Piessen G, Briez N, Triboulet JP. The number of metastatic lymph nodes and the ratio between metastatic and examined lymph nodes are independent prognostic factors in esophageal cancer regardless of neoadjuvant chemoradiation or lymphadenectomy extent. Ann Surg 2008; 247:365.
  29. Bogoevski D, Onken F, Koenig A, et al. Is it time for a new TNM classification in esophageal carcinoma? Ann Surg 2008; 247:633.
  30. van Vliet EP, Heijenbrok-Kal MH, Hunink MG, et al. Staging investigations for oesophageal cancer: a meta-analysis. Br J Cancer 2008; 98:547.
  31. Lowe VJ, Booya F, Fletcher JG, et al. Comparison of positron emission tomography, computed tomography, and endoscopic ultrasound in the initial staging of patients with esophageal cancer. Mol Imaging Biol 2005; 7:422.
  32. Rice TW. Clinical staging of esophageal carcinoma. CT, EUS, and PET. Chest Surg Clin N Am 2000; 10:471.
  33. Rösch T. Endosonographic staging of esophageal cancer: a review of literature results. Gastrointest Endosc Clin N Am 1995; 5:537.
  34. Chandawarkar RY, Kakegawa T, Fujita H, et al. Endosonography for preoperative staging of specific nodal groups associated with esophageal cancer. World J Surg 1996; 20:700.
  35. Young PE, Gentry AB, Acosta RD, et al. Endoscopic ultrasound does not accurately stage early adenocarcinoma or high-grade dysplasia of the esophagus. Clin Gastroenterol Hepatol 2010; 8:1037.
  36. Vazquez-Sequeiros E, Wiersema MJ, Clain JE, et al. Impact of lymph node staging on therapy of esophageal carcinoma. Gastroenterology 2003; 125:1626.
  37. Rice TW, Blackstone EH, Adelstein DJ, et al. Role of clinically determined depth of tumor invasion in the treatment of esophageal carcinoma. J Thorac Cardiovasc Surg 2003; 125:1091.
  38. Flamen P, Lerut A, Van Cutsem E, et al. Utility of positron emission tomography for the staging of patients with potentially operable esophageal carcinoma. J Clin Oncol 2000; 18:3202.
  39. Keswani RN, Early DS, Edmundowicz SA, et al. Routine positron emission tomography does not alter nodal staging in patients undergoing EUS-guided FNA for esophageal cancer. Gastrointest Endosc 2009; 69:1210.
  40. Brugge WR, Lee MJ, Carey RW, Mathisen DJ. Endoscopic ultrasound staging criteria for esophageal cancer. Gastrointest Endosc 1997; 45:147.
  41. Hünerbein M, Ghadimi BM, Haensch W, Schlag PM. Transendoscopic ultrasound of esophageal and gastric cancer using miniaturized ultrasound catheter probes. Gastrointest Endosc 1998; 48:371.
  42. Boonstra JJ, Koppert LB, Wijnhoven BP, et al. Chemotherapy followed by surgery in patients with carcinoma of the distal esophagus and celiac lymph node involvement. J Surg Oncol 2009; 100:407.
  43. Sun F, Chen T, Han J, et al. Staging accuracy of endoscopic ultrasound for esophageal cancer after neoadjuvant chemotherapy: a meta-analysis and systematic review. Dis Esophagus 2015; 28:757.
  44. Sarkaria IS, Rizk NP, Bains MS, et al. Post-treatment endoscopic biopsy is a poor-predictor of pathologic response in patients undergoing chemoradiation therapy for esophageal cancer. Ann Surg 2009; 249:764.
  45. Schneider PM, Metzger R, Schaefer H, et al. Response evaluation by endoscopy, rebiopsy, and endoscopic ultrasound does not accurately predict histopathologic regression after neoadjuvant chemoradiation for esophageal cancer. Ann Surg 2008; 248:902.
  46. Isenberg G, Chak A, Canto MI, et al. Endoscopic ultrasound in restaging of esophageal cancer after neoadjuvant chemoradiation. Gastrointest Endosc 1998; 48:158.
  47. Chak A, Canto MI, Cooper GS, et al. Endosonographic assessment of multimodality therapy predicts survival of esophageal carcinoma patients. Cancer 2000; 88:1788.
  48. Willis J, Cooper GS, Isenberg G, et al. Correlation of EUS measurement with pathologic assessment of neoadjuvant therapy response in esophageal carcinoma. Gastrointest Endosc 2002; 55:655.
  49. Meltzer CC, Luketich JD, Friedman D, et al. Whole-body FDG positron emission tomographic imaging for staging esophageal cancer comparison with computed tomography. Clin Nucl Med 2000; 25:882.
  50. Romagnuolo J, Scott J, Hawes RH, et al. Helical CT versus EUS with fine needle aspiration for celiac nodal assessment in patients with esophageal cancer. Gastrointest Endosc 2002; 55:648.
  51. Flanagan FL, Dehdashti F, Siegel BA, et al. Staging of esophageal cancer with 18F-fluorodeoxyglucose positron emission tomography. AJR Am J Roentgenol 1997; 168:417.
  52. Block MI, Patterson GA, Sundaresan RS, et al. Improvement in staging of esophageal cancer with the addition of positron emission tomography. Ann Thorac Surg 1997; 64:770.
  53. Luketich JD, Friedman DM, Weigel TL, et al. Evaluation of distant metastases in esophageal cancer: 100 consecutive positron emission tomography scans. Ann Thorac Surg 1999; 68:1133.
  54. Meyers BF, Downey RJ, Decker PA, et al. The utility of positron emission tomography in staging of potentially operable carcinoma of the thoracic esophagus: results of the American College of Surgeons Oncology Group Z0060 trial. J Thorac Cardiovasc Surg 2007; 133:738.
  55. Räsänen JV, Sihvo EI, Knuuti MJ, et al. Prospective analysis of accuracy of positron emission tomography, computed tomography, and endoscopic ultrasonography in staging of adenocarcinoma of the esophagus and the esophagogastric junction. Ann Surg Oncol 2003; 10:954.
  56. van Westreenen HL, Heeren PA, van Dullemen HM, et al. Positron emission tomography with F-18-fluorodeoxyglucose in a combined staging strategy of esophageal cancer prevents unnecessary surgical explorations. J Gastrointest Surg 2005; 9:54.
  57. Wren SM, Stijns P, Srinivas S. Positron emission tomography in the initial staging of esophageal cancer. Arch Surg 2002; 137:1001.
  58. Wallace MB, Nietert PJ, Earle C, et al. An analysis of multiple staging management strategies for carcinoma of the esophagus: computed tomography, endoscopic ultrasound, positron emission tomography, and thoracoscopy/laparoscopy. Ann Thorac Surg 2002; 74:1026.
  59. Bruzzi JF, Truong MT, Macapinlac H, et al. Integrated CT-PET imaging of esophageal cancer: unexpected and unusual distribution of distant organ metastases. Curr Probl Diagn Radiol 2007; 36:21.
  60. Erasmus JJ, Munden RF. The role of integrated computed tomography positron-emission tomography in esophageal cancer: staging and assessment of therapeutic response. Semin Radiat Oncol 2007; 17:29.
  61. Pan L, Gu P, Huang G, et al. Prognostic significance of SUV on PET/CT in patients with esophageal cancer: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2009; 21:1008.
  62. Rizk NP, Tang L, Adusumilli PS, et al. Predictive value of initial PET-SUVmax in patients with locally advanced esophageal and gastroesophageal junction adenocarcinoma. J Thorac Oncol 2009; 4:875.
  63. Kwee RM. Prediction of tumor response to neoadjuvant therapy in patients with esophageal cancer with use of 18F FDG PET: a systematic review. Radiology 2010; 254:707.
  64. Mawlawi O, Erasmus JJ, Munden RF, et al. Quantifying the effect of IV contrast media on integrated PET/CT: clinical evaluation. AJR Am J Roentgenol 2006; 186:308.
  65. Bruzzi JF, Swisher SG, Truong MT, et al. Detection of interval distant metastases: clinical utility of integrated CT-PET imaging in patients with esophageal carcinoma after neoadjuvant therapy. Cancer 2007; 109:125.
  66. Roedl JB, Colen RR, Holalkere NS, et al. Adenocarcinomas of the esophagus: response to chemoradiotherapy is associated with decrease of metabolic tumor volume as measured on PET-CT. Comparison to histopathologic and clinical response evaluation. Radiother Oncol 2008; 89:278.
  67. Westerterp M, van Westreenen HL, Reitsma JB, et al. Esophageal cancer: CT, endoscopic US, and FDG PET for assessment of response to neoadjuvant therapy--systematic review. Radiology 2005; 236:841.
  68. Cerfolio RJ, Bryant AS, Ohja B, et al. The accuracy of endoscopic ultrasonography with fine-needle aspiration, integrated positron emission tomography with computed tomography, and computed tomography in restaging patients with esophageal cancer after neoadjuvant chemoradiotherapy. J Thorac Cardiovasc Surg 2005; 129:1232.
  69. Jones DR, Parker LA Jr, Detterbeck FC, Egan TM. Inadequacy of computed tomography in assessing patients with esophageal carcinoma after induction chemoradiotherapy. Cancer 1999; 85:1026.
  70. Flamen P, Van Cutsem E, Lerut A, et al. Positron emission tomography for assessment of the response to induction radiochemotherapy in locally advanced oesophageal cancer. Ann Oncol 2002; 13:361.
  71. Kato H, Kuwano H, Nakajima M, et al. Usefulness of positron emission tomography for assessing the response of neoadjuvant chemoradiotherapy in patients with esophageal cancer. Am J Surg 2002; 184:279.
  72. Weber WA, Ott K, Becker K, et al. Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol 2001; 19:3058.
  73. Song SY, Kim JH, Ryu JS, et al. FDG-PET in the prediction of pathologic response after neoadjuvant chemoradiotherapy in locally advanced, resectable esophageal cancer. Int J Radiat Oncol Biol Phys 2005; 63:1053.
  74. Levine EA, Farmer MR, Clark P, et al. Predictive value of 18-fluoro-deoxy-glucose-positron emission tomography (18F-FDG-PET) in the identification of responders to chemoradiation therapy for the treatment of locally advanced esophageal cancer. Ann Surg 2006; 243:472.
  75. Patnana SV, Murthy SB, Xiao L, et al. Critical role of surgery in patients with gastroesophageal carcinoma with a poor prognosis after chemoradiation as defined by positron emission tomography. Cancer 2010; 116:4487.
  76. Monjazeb AM, Riedlinger G, Aklilu M, et al. Outcomes of patients with esophageal cancer staged with [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET): can postchemoradiotherapy FDG-PET predict the utility of resection? J Clin Oncol 2010; 28:4714.
  77. Downey RJ, Akhurst T, Ilson D, et al. Whole body 18FDG-PET and the response of esophageal cancer to induction therapy: results of a prospective trial. J Clin Oncol 2003; 21:428.
  78. Vallböhmer D, Hölscher AH, Dietlein M, et al. [18F]-Fluorodeoxyglucose-positron emission tomography for the assessment of histopathologic response and prognosis after completion of neoadjuvant chemoradiation in esophageal cancer. Ann Surg 2009; 250:888.
  79. McLoughlin JM, Melis M, Siegel EM, et al. Are patients with esophageal cancer who become PET negative after neoadjuvant chemoradiation free of cancer? J Am Coll Surg 2008; 206:879.
  80. Wieder HA, Brücher BL, Zimmermann F, et al. Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment. J Clin Oncol 2004; 22:900.
  81. Konski AA, Cheng JD, Goldberg M, et al. Correlation of molecular response as measured by 18-FDG positron emission tomography with outcome after chemoradiotherapy in patients with esophageal carcinoma. Int J Radiat Oncol Biol Phys 2007; 69:358.
  82. Kaushik N, Khalid A, Brody D, et al. Endoscopic ultrasound compared with laparoscopy for staging esophageal cancer. Ann Thorac Surg 2007; 83:2000.
  83. Yau KK, Siu WT, Cheung HY, et al. Immediate preoperative laparoscopic staging for squamous cell carcinoma of the esophagus. Surg Endosc 2006; 20:307.
  84. Bryan RT, Cruickshank NR, Needham SJ, et al. Laparoscopic peritoneal lavage in staging gastric and oesophageal cancer. Eur J Surg Oncol 2001; 27:291.
  85. Krasna MJ, Reed CE, Nedzwiecki D, et al. CALGB 9380: a prospective trial of the feasibility of thoracoscopy/laparoscopy in staging esophageal cancer. Ann Thorac Surg 2001; 71:1073.
  86. Krasna MJ, Jiao X, Mao YS, et al. Thoracoscopy/laparoscopy in the staging of esophageal cancer: Maryland experience. Surg Laparosc Endosc Percutan Tech 2002; 12:213.
  87. Luketich JD, Schauer P, Landreneau R, et al. Minimally invasive surgical staging is superior to endoscopic ultrasound in detecting lymph node metastases in esophageal cancer. J Thorac Cardiovasc Surg 1997; 114:817.
  88. Lordick F, Mariette C, Haustermans K, et al. Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016; 27:v50.
  89. Finch MD, John TG, Garden OJ, et al. Laparoscopic ultrasonography for staging gastroesophageal cancer. Surgery 1997; 121:10.
  90. Wakelin SJ, Deans C, Crofts TJ, et al. A comparison of computerised tomography, laparoscopic ultrasound and endoscopic ultrasound in the preoperative staging of oesophago-gastric carcinoma. Eur J Radiol 2002; 41:161.
  91. Samee A, Moorthy K, Jaipersad T, et al. Evaluation of the role of laparoscopic ultrasonography in the staging of oesophagogastric cancers. Surg Endosc 2009; 23:2061.
  92. National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
  93. Riedel M, Hauck RW, Stein HJ, et al. Preoperative bronchoscopic assessment of airway invasion by esophageal cancer: a prospective study. Chest 1998; 113:687.