Clinical Review

Esophageal Cancer: Current Diagnosis and Management

Journal of Clinical Outcomes Management. 2014 August;21(8)

References

1. Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. http://globocan.iarc.fr. Accessed on May 5, 2014.

2. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64:9–29.

3. Nieman DR, Peters JH. Treatment strategies for esophageal cancer. Gastroenterol Clin North Am 2013;42:187–97.

4. Shridhar R, Almhanna K, Meredith KL, et al. Radiation therapy and esophageal cancer. Cancer Control 2013;20:97–110.

5. 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;97:1471–8.

6. Rubenstein JH, Taylor JB. Meta-analysis: the association of oesophagealadenocarcinoma with symptoms of gastro-oesophageal reflux. Aliment Pharmacol Ther 2010;32:1222–7.

7. Lagergren J, Bergström R, Lindgren A, Nyrén O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999;340:825–31.

8. Pohl H, Wrobel K, Bojarski C, et al. Risk factors in the development of esophageal adenocarcinoma. Am J Gastroenterol 2013;108:200–7.

9. Coleman HG, Bhat SK, Murray LJ, et al. Symptoms and endoscopic features at Barrett’s esophagus diagnosis: implications for neoplastic progression risk. Am J Gastroenterol 2014;109:527–34.

10. Nguyen DM, El-Serag HB, Henderson L, et al. Medication usage and the risk of neoplasia in patients with Barrett’s esophagus. Clin Gastroenterol Hepatol 2009;7:1299–304.

11. Lagergren J, Ye W, Lagergren P, Lu Y. The risk of esophageal adenocarcinomaafter antireflux surgery. Gastroenterology 2010;138:1297–301.

12. el-Serag HB. The epidemic of esophageal adenocarcinoma. Gastroenterol Clin North Am 2002;31:421–40, viii.

13. Abnet CC, Freedman ND, Hollenbeck AR, et al. A prospective study of BMI and risk of oesophageal and gastric adenocarcinoma. Eur J Cancer 2008;44:465–71.

14. Turati F, Tramacere I, La Vecchia C, Negri E. A meta-analysis of body mass index and esophageal and gastric cardia adenocarcinoma. Ann Oncol 2013;24:609–17.

15. Kroep S, Lansdorp-Vogelaar I, Rubenstein JH, et al. Comparing trends in esophageal adenocarcinoma incidence and lifestyle factors between the United States, Spain, and the Netherlands. Am J Gastroenterol 2014;109:336–43.

16. Cook MB, Kamangar F, Whiteman DC, et al. Cigarette smoking and adenocarcinomas of the esophagus and esophagogastric junction: a pooled analysis from the international BEACON consortium. J Natl Cancer Inst 2010;102:1344–53.

17. Kubo A, Levin TR, Block G, et al. Dietary antioxidants, fruits, and vegetables and the risk of Barrett’s esophagus. Am J Gastroenterol 2008;103:1614–23.

18. Freedman ND, Abnet CC, Leitzmann MF, et al. A prospective study of tobacco, alcohol, and the risk of esophageal and gastric cancer subtypes. Am J Epidemiol 2007;165:1424–33.

19. Pandeya N, Williams G, Green AC, et al; Australian Cancer Study. Alcohol consumption and the risks of adenocarcinoma and squamous cell carcinoma of the esophagus. Gastroenterology 2009;136:1215–24, e1-2.

20. Kamangar F, Chow WH, Abnet CC, Dawsey SM. Environmental causes of esophageal cancer. Gastroenterol Clin North Am 2009;38:27–57, vii.

21. Pandeya N, Williams GM, Sadhegi S, et al. Associations of duration, intensity, and quantity of smoking with adenocarcinoma and squamous cell carcinoma of the esophagus. Am J Epidemiol 2008;168:105–14.

22. Boffetta P, Hecht S, Gray N, et al. Smokeless tobacco and cancer. Lancet Oncol 2008;9:667–75.

23. Dar NA, Bhat GA, Shah IA, eta l. Hookah smoking, nass chewing, and oesophageal squamous cell carcinoma in Kashmir, India. Br J Cancer 2012;107:1618–23.

24. Abnet CC, Kamangar F, Islami F, et al. Tooth loss and lack of regular oral hygiene are associated with higher risk of esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 2008;17:3062–8.

25. Islami F, Sheikhattari P, Ren JS, Kamangar F. Gastric atrophy and risk of oesophageal cancer and gastric cardia adenocarcinoma--a systematic review and meta-analysis. Ann Oncol 2011;22:754–60.

26. Appelqvist P, Salmo M. Lye corrosion carcinoma of the esophagus: a review of 63 cases. Cancer 1980;45:2655–8.

27. Sandler RS, Nyrén O, Ekbom A, et al. The risk of esophageal cancer in patients with achalasia. A population-based study. JAMA 1995;274:1359–62.

28. Lu SH, Montesano R, Zhang MS, et al. Relevance of N-nitrosamines to esophageal cancer in China. J Cell Physiol Suppl 1986;4:51–8.

29. Steevens J, van den Brandt PA, Goldbohm RA, Schouten LJ. Selenium status and the risk of esophageal and gastric cancer subtypes: the Netherlands cohort study. Gastroenterology 2010;138:1704–13.

30. Abnet CC, Lai B, Qiao YL, et al. Zinc concentration in esophageal biopsy specimens measured by x-ray fluorescence and esophageal cancer risk. J Natl Cancer Inst 2005;97:301–6.

31. Islami F, Boffetta P, Ren JS, et al. High-temperature beverages and foods and esophageal cancer risk--a systematic review. Int J Cancer 2009;125:491–524.

32. Liu J, Wang J, Leng Y, Lv C. Intake of fruit and vegetables and risk of esophageal squamous cell carcinoma: a meta-analysis of observational studies. Int J Cancer 2013;133:473–85.

33. Corley DA, Kerlikowske K, Verma R, Buffler P. Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis. Gastroenterology 2003;124:47–56.

34. Ratnasinghe D, Tangrea J, Roth MJ, et al. Expression of cyclooxygenase-2 in human squamous cell carcinoma of the esophagus; an immunohistochemical survey. Anticancer Res 1999;19:171–4.

35. Morris CD, Armstrong GR, Bigley G, et al. Cyclooxygenase-2 expression in the Barrett’s metaplasia-dysplasia-adenocarcinoma sequence. Am J Gastroenterol 2001;96:990–6.

36. Daly JM, Fry WA, Little AG, et al. Esophageal cancer: results of an American College of Surgeons Patient Care Evaluation Study. J Am Coll Surg 2000;190:562–72.

37. Gastrointestinal cancer. In: Fishman MC, Hoffman R, Klausner RD, Thaler MS, editors. Medicine. 5th ed. Baltimore: Lippincott Williams & Wilkins; 2002:423–6.

38. Fein R, Kelsen DP, Geller N, et al. Adenocarcinoma of the esophagus and gastroesophageal junction. Prognostic factors and results of therapy. Cancer 1985;56:2512–8.

39. Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med 2003;349:2241–52.

40. Lightdale CJ. Esophageal cancer. Am J Gastroenterol 1999;94:20–9.

41. Graham DY, Schwartz JT, Cain GD, Gyorkey F. Prospective evaluation of biopsy number in the diagnosis of esophageal and gastric carcinoma. Gastroenterology 1982;82:228–31.

42. 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;7:422–30.

43. Röesch T. Endoscopic ultrasonography: equipment and technique. Gastrointest Endosc Clin N Am 2005;15:13–31, vii.

44. Vazquez-Sequeiros E, Norton ID, Clain JE, et al. Impact of EUS-guided fine-needle aspiration on lymph node staging in patients with esophageal carcinoma. Gastrointest Endosc 2001;53:751–7.

45. Van Dam J. Endosonographic evaluation of the patient with esophageal cancer. Chest 1997;112(4 Suppl):184S–190S.

46. Catalano MF, Van Dam J, Sivak MV Jr. Malignant esophageal strictures: staging accuracy of endoscopic ultrasonography. Gastrointest Endosc 1995;41:535–9.

47. Van Dam J, Rice TW, Catalano MF, et al. High-grade malignant stricture is predictive of esophageal tumor stage. Risks of endosonographic evaluation. Cancer 1993;71:2910–7.

48. Hünerbein M, Ghadimi BM, Haensch W, Schlag PM. Transendoscopic ultrasound of esophageal and gastric cancer using miniaturized ultrasound catheter probes. Gastrointest Endosc 1998;48:371–5.

49. Zuccaro G Jr, Rice TW, Goldblum J, et al. Endoscopic ultrasound cannot determine suitability for esophagectomy after aggressive chemoradiotherapy for esophageal cancer. Am J Gastroenterol 1999;94:906–12.

50. ASGE Standards of Practice Committee, Evans JA, Early DS, Chandraskhara V, et al; American Society for Gastrointestinal Endoscopy. The role of endoscopy in the assessment and treatment of esophageal cancer. Gastrointest Endosc 2013;77:328–34.

51. 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;114:817–21.

52. Krasna MJ, Flowers JL, Attar S, McLaughlin J. Combined thoracoscopic/laparoscopic staging of esophageal cancer. J Thorac Cardiovasc Surg 1996;111:800–6.

53. 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;18:3202–10.

54. 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;21:428–32.

55. Mealy K, Feely J, Reid I, et al. Tumour marker detection in oesophageal carcinoma. Eur J Surg Oncol 1996;22:505–7.

56. Rice TW, Rusch VW, Ishwaran H, Blackstone EH; Worldwide Esophageal Cancer Collaboration. 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;116:3763–73.

57. Edge SB, Byrd DR, Compton CC, et al, eds. AJCC cancer staging manual. 7th ed. New York: Springer-Verlag; 2009:103–5.

58. Rice TW, Rusch VW, Apperson-Hansen C, et al. Worldwide esophageal cancer collaboration. Dis Esophagus 2009;22:1–8.

59. Villaflor VM, Allaix ME, Minsky B, et al. Multidisciplinary approach for patients with esophageal cancer. World J Gastroenterol 2012;18:6737–46.

60. Ngamruengphong S, Wolfsen HC, Wallace MB. Survival of patients with superficial esophageal adenocarcinoma after endoscopic treatment vs surgery. Clin Gastroenterol Hepatol 2013;11:1424–9.e2.

61. Lin SH, Chang JY. Esophageal cancer: diagnosis and management. Chin J Cancer 2010;29:843–54.

62. Prasad GA, Wu TT, Wigle DA, et al. Endoscopic and surgical treatment of mucosal (T1a) esophageal adenocarcinoma in Barrett’s esophagus. Gastroenterology 2009;137:815–23.

63. Das A, Singh V, Fleischer DE, Sharma VK. A comparison of endoscopic treatment and surgery in early esophageal cancer: an analysis of surveillance epidemiology and end results data. Am J Gastroenterol 2008;103:1340–5.

64. Herskovic A, Martz K, al-Sarraf M, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 1992;326:1593–8.

65. Gebski V, Burmeister B, Smithers BM, et al; Australasian Gastro-Intestinal Trials Group. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol 2007;8:226–34.

66. Bedenne L, Michel P, Bouché O, et al. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 2007;25:1160–8.

67. Tougeron D, Scotté M, Hamidou H, et al. Definitive chemoradiotherapy in patients with esophageal adenocarcinoma: an alternative to surgery? J Surg Oncol 2012;105: 761–6.

68. Siddiqui AA, Sarkar A, Beltz S, et al. Placement of fully covered self-expandable metal stents in patients with locally advanced esophageal cancer before neoadjuvant therapy. Gastrointest Endosc 2012;76:44–51.

69. Nagaraja V, Cox MR, Eslick GD. Safety and efficacy of esophageal stents preceding or during neoadjuvant chemotherapy for esophageal cancer: a systematic review and meta-analysis. J Gastrointest Oncol 2014;5:119–26.

70. Adler DG, Fang J, Wong R, et al. Placement of Polyflex stents in patients with locally advanced esophageal cancer is safe and improves dysphagia during neoadjuvant therapy. Gastrointest Endosc 2009;70:614–9.

71. Dubecz A, Sepesi B, Salvador R, et al. Surgical resection for locoregional esophageal cancer is underutilized in the United States. J Am Coll Surg 2010;211:754–61.

72. Hulscher JB, Tijssen JG, Obertop H, van Lanschot JJ. Transthoracic versus transhiatal resection for carcinoma of the esophagus: a meta-analysis. Ann Thorac Surg 2001;72:306–13.

73. Chang AC, Ji H, Birkmeyer NJ, et al. Outcomes after transhiatal and transthoracic esophagectomy for cancer. Ann Thorac Surg 2008;85:424–9.

74. Almhanna K, Shridhar R, Meredith KL. Neoadjuvant or adjuvant therapy for resectable esophageal cancer: is there a standard of care? Cancer Control 2013;20:89–96.

75. Harvey JA, Bessell JR, Beller E, et al. Chemoradiation therapy is effective for the palliative treatment of malignant dysphagia. Dis Esophagus 2004;17:260–5.

76. Siersema PD, Schrauwen SL, van Blankenstein M, et al; Rotterdam Esophageal Tumor Study Group. Self-expanding metal stents for complicated and recurrent esophagogastric cancer. Gastrointest Endosc 2001;54:579–86.

77. Homs MY, Steyerberg EW, Eijkenboom WM, et al. Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia from oesophageal cancer: multicentre randomised trial. Lancet 2004;364(9444):1497–504.

78. van den Bongard HJ, Boot H, Baas P, Taal BG. The role of parallel stent insertion in patients with esophagorespiratory fistulas. Gastrointest Endosc 2002;55:110–5.

79. Siegel R, DeSantis C, Virgo K, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin 2012;62:220–41.

80. Fein R, Kelsen DP, Geller N, et al. Adenocarcinoma of the esophagus and gastroesophageal junction. Prognostic factors and results of therapy. Cancer 1985;56:2512–8.

81. Mariette C, Maurel A, Fabre S, et al. [Preoperative prognostic factors for squamous cell carcinomas of the thoracic esophagus]. Gastroenterol Clin Biol 2001;25:468–72.

82. Swanson SJ, Batirel HF, Bueno R, et al. Transthoracic esophagectomy with radical mediastinal and abdominal lymph node dissection and cervical esophagogastrostomy for esophageal carcinoma. Ann Thorac Surg 2001;72:1918–24.

83. Urba SG, Orringer MB, Turrisi A, et al. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001;19:305–13.

84. Hosch SB, Stoecklein NH, Pichlmeier U, et al. Esophageal cancer: the mode of lymphatic tumor cell spread and its prognostic significance. J Clin Oncol 2001;19:1970–5.

Looking for distant metastasis, or M staging, is carried out with EUS, diagnostic laparoscopy/thoracoscopy, and CT and/or positron emission tomography (PET) scans. Despite the high accuracy of esophageal cancer staging with laparoscopy and thoracoscopy, these are invasive procedures and have generally been replaced by PET scan [39,51,52]. PET with 18F-fludeoxyglucose has been shown to significantly improve the detection rate of metastatic disease compared with the conventional staging methods (CT scan and EUS) [53]. In a prospective study, PET scans detected metastasis in 15% of patients who were thought to have localized cancer by conventional staging modalities [39,54].

Unlike several other cancers, tumor markers such as carbohydrate antigen (CA) 19-9, CA 125, and carcinoembryonic antigen (CEA) have low specificity and sensitivity in esophageal cancer and are not routinely obtained and/or followed [39,55].

Staging

In the 2010 edition of esophageal cancer staging from the American Joint Committee on Cancer (AJCC), the committee made changes to the staging of cancer based on a new database of esophagectomy patients from the Worldwide Esophageal Cancer Collaboration [56–58].Previous versions of the TNM staging system were based on orderly arrangement of increasing anatomic tumor, then node, then metastasis, which was not always consistent with cancer biology [56].The 2010 guidelines are based on risk-adjusted random forest statistical analysis of worldwide data (machine-learning method that focuses on predictability for future patients) [56,57].The current guidelines now take into account development of separate stage groups based on histopathologic cell type (ie, adeno-carcinoma versus SCC), histologic grade, and tumor location ( Table 1 and Table 2) [56].

Treatment

Early Stage

Historically, patients with early stage esophageal cancer (those without evidence of deep invasion into the esophageal wall and no evidence of peritumoral malignant adenopathy or metastases, typically T1N0M0) were referred for esophagectomy [59]. Recent treatment trends suggest proportionately more patients with T1 disease are being treated endoscopically (up to 29% of patients) and proportionately fewer with esophagectomy [60]. EMR has emerged as a viable alternative treatment to esophagectomy when the lesion is staged T1aN0 (tumor invading the lamina propria or muscularis mucosae but not the submucosa) [3]. EMR is performed via several techniques, but most commonly as follows. First, saline is injected under the lesion to create a submucosal cushion, separating the lesion from the underlying muscularis propria. The actual endoscopic resection of the lesion is usually accomplished via snare electrocautery and the resected lesion is sent for pathologic analysis. Endoscopic caps and band ligation devices are available to facilitate removal of the lesion in one or more pieces [61].

In a retrospective cohort study by Prasad et al of 178 patients from 1998 to 2007, the cumulative mortality in the EMR group was comparable to that of the surgery group (17% vs. 20%, respectively, P = 0.75) [62]. Recurrent cancer was detected in 12% of EMR patients; however, all patients were successfully re-treated without affecting overall survival.

In another study of 742 patients, long-term survival in those with early esophageal cancer managed with endoscopic therapy was comparable to that in patients treated with surgical resection [63]. The median cancer-free survival in the endoscopic group was not significantly different from that in the surgical group (56 and 59 months, respectively, P = 0.41) The study found that the relative hazard for 1esophageal cancer–specific mortality in the endoscopic group did not differ from that of the surgical group (relative hazard, 0.89; 95% CI, 0.51 to 1.56; P = 0.68).