Esophageal Cancer Guidelines 

Updated: Mar 08, 2017
  • Author: Elwyn C Cabebe, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Prevention

Squamous cell carcinoma of the esophagus and adenocarcinoma of the esophagus have different risk factors and thus require different approaches to prevention. For esophageal squamous cell carcinoma, the major environmental risk factors are cigarette smoking and alcohol abuse, accounting for up to 90% of cases in the United States. Both the National Comprehensive Cancer Network (NCCN) guidelines and the National Cancer Institute (NCI) PDQ cancer information summary for esophageal cancer prevention conclude that smoking cessation decreases the risk of squamous cell carcinoma. [1, 2]

Gastroesophageal reflux disease (GERD) and Barrett esophagus significantly increase the risk for development of adenocarcinoma of the esophagus. According to the NCI, however, eliminating GERD has an unknown impact on subsequent risk of developing adenocarcinoma. [2]

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Screening and Surveillance

Recommendations for screening and surveillance of patients with GERD and/or Barrett esophagus have been issued by the following organizations:

  • American Society for Gastrointestinal Endoscopy (ASGE)
  • American Gastroenterological Association (AGA)
  • American College of Gastroenterology (ACG)
  • American College of Physicians (ACP)

None of the organizations recommend endoscopic screening of the general population with GERD. There is general agreement among the guidelines that patients with chronic GERD and multiple other risk factors associated with esophageal adenocarcinoma should undergo upper gastrointestinal endoscopy to screen for Barrett esophagus or esophageal adenocarcinoma. [3, 4, 5, 6, 7] Those additional risk factors include the following:

  • Male sex
  • Age 50 years or older
  • White race
  • Hiatal hernia
  • Obesity

The 2015 American Society for Gatrointestinal Endoscopy (ASGE) guidelines for the use of endoscopy in the management of GERD recommends endoscopic screening in select patients with multiple risk factors for Barrett esophagus be considered, but also advises that patients be informed that there is insufficient evidence that this practice prevents cancer or prolongs survival. [7]

The American College of Physicians' (ACP) best practice advice, issued in 2012, offers the following recommendations for upper endoscopy for GERD: [6]

  • Screening endoscopy is not recommended for women of any age or men younger than 50, regardless of other risk factors, because of the low incidence of cancer in these populations
  • Screening is recommended in both men and women with GERD symptoms despite medical treatment, and especially in those with GERD and dysphagia, bleeding, anemia, weight loss, or recurrent vomiting
  • No further surveillance is recommended if endoscopy shows negative results for Barrett esophagus
  • In patients with Barrett esophagus and no dysplasia, surveillance examinations should occur at intervals of 3 to 5 years; shorter intervals are indicated in patients with Barrett esophagus and dysplasia

Additional recommendations from  the 2012 ASGE guidelines for use of endoscopy in Barrett esophagus include the following [3] :

  • No further surveillance is recommended if screening endoscopy shows negative results for Barrett esophagus or adenocarcinoma
  • For patients with nondysplastic Barrett esophagus, endoscopic surveillance should be performed every 3 to 5 years, and include biopsy of the lesion
  • For patients with low-grade dysplasia, repeat endoscopy within 6 months to confirm the diagnosis, then annual endoscopy and biopsy; consider ablation
  • For patients with high-grade dysplasia, eradication with endoscopic resection is indicated; radiofrequency ablation (RFA) may be considered for flat lesions in select cases; surveillance is appropriate only for patients unfit or unwilling for surgery or ablation.

The American Gastroenterological Association's (AGA) 2011 position statement on the management of Barrett esophagus generally concurs with the ASGE guidelines, but includes the following surveillance interval recommendation: [4]

  • No dysplasia: 3-5 years
  • Low-grade dysplasia: 6-12 months
  • High-grade dysplasia in the absence of eradication therapy: 3 months

In addition, the guidelines recommend endoscopic eradication therapy with RFA, photodynamic therapy (PDT), or endoscopic mucosal resection (EMR) rather than surveillance for patients with high-grade dysplasia. [4]

The American College of Gastroenterology (ACG) published updated guidelines for diagnosis, surveillance, and therapy of Barrett esophagus in 2015. The ACG recommends that endoscopic ablative therapies should not be routinely used in patients with nondysplastic Barrett esophagus, because of their low risk of progression to esophageal adenocarcinoma (strong recommendation, very low level of evidence). However, endoscopic eradication therapy is the procedure of choice for patients with confirmed dysplasia, whether low or high grade. The ACG advises that antireflux surgery should not be used as an antineoplastic measure. [5]

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Diagnosis

In 2013, the Society of Thoracic Surgeons released clinical practice guidelines to assist in the diagnosis and staging of esophageal cancer. Their recommendations include the following [8] :

  • For the diagnosis of esophageal cancer, flexible endoscopy with biopsy is the test of choice
  • For early-stage esophageal cancer, computed tomography (CT) of the chest and abdomen is an optional test for staging
  • For locoregionalized esophageal cancer, CT of the chest and abdomen is a recommended test for staging
  • For early-stage esophageal cancer, positron emission tomography (PET) is an optional test for staging
  • For locoregionalized esophageal cancer, PET is a recommended test for staging
  • In patients without metastatic disease, endoscopic ultrasonography is recommended to improve the accuracy of staging
  • In patients with small, discrete nodules or areas of dysplasia in whom disease appears limited to the mucosa or submucosa (as assessed by endoscopic ultrasonography), endoscopic mucosal resection (EMR) should be considered as a diagnostic/staging tool
  • In patients with locally advanced (T3/T4) adenocarcinoma of the esophagogastric junction infiltrating the anatomic cardia or Siewart type III esophagogastric tumors, laparoscopy is recommended to improve accuracy of staging

The 2013 American Society for Gastrointestinal Endoscopy (ASGE) guidelines for use of endoscopy in the assessment and treatment of esophageal cancer make the following recommendations for accurate staging [9] :

  • Endoscopic ultrasound and fine needle aspiration (FNA), when indicated, in conjunction with cross-sectional imaging is preferred over CT
  • Endoscopic mucosal or submucosal dissection is indicated for the treatment and staging of nodular Barrett esophagus and suspected squamous cell carcinoma and adenocarcinoma

The 2015 American College of Gastroenterology guidelines on Barrett esophagus include the following recommend that routine staging of patients with nodular Barrett esophagus with endoscopic ultrasound or other imaging modalities before EMR has no demonstrated benefit. Given the possibility of over- and understaging, the ACG advises that findings of these modalities should not preclude the performance of EMR to stage early neoplasia (strong recommendation, moderate level of evidence). [5]

For information on staging, see Esophageal Cancer Staging.

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Treatment

American College of Gastroenterology (ACG) recommendations regarding endoscopic treatment of Barrett esophagus include the following [5] :

  • In patients with T1a esophageal adenocarcinoma, endoscopic therapy is the preferred therapeutic approach (strong recommendation, moderate level of evidence)
  • In patients with T1b esophageal adenocarcinoma, consultation with multidisciplinary surgical oncology team should occur before embarking on endoscopic therapy; in such patients, endoscopic therapy may be an alternative strategy to esophagectomy, especially in those with superficial (sm1) disease with a well-differentiated neoplasm lacking lymphovascular invasion, as well as those who are poor surgical candidates (strong recommendation, low level of evidence)
  • In patients with known T1b disease, EUS may have a role in assessing and sampling regional lymph nodes, given the increased prevalence of lymph node involvement in these patients compared with less advanced disease (strong recommendation, moderate level of evidence)
  • In patients with dysplastic Barrett esophagus who are to undergo endoscopic ablative therapy for nonnodular disease, radiofrequency ablation is currently the preferred endoscopic ablative therapy (strong recommendation, moderate level of evidence).

ACG recommendations for surgical therapy are as follows [5] :

  • In esophageal adenocarcinoma with invasion into the submucosa, especially with invasion to the mid or deep submucosa (T1b, sm2–3), esophagectomy, with consideration of neoadjuvant therapy, is recommended in patients who are surgical candidates (strong recommendation, low level of evidence)
  • In patients with T1a or T1b sm1 adenocarcinoma, poor differentiation, lymphovascular invasion, or incomplete endoscopic mucosal resection should prompt consideration of surgical and/or multimodality therapies (strong recommendation, low level of evidence)

National Comprehensive Cancer Network (NCCN) treatment recommendations include the following [1] :

  • Endoscopic therapy (endoscopic mucosal resection, endoscopic submucosal dissection and/or ablation) is preferred for high-grade dysplasia (HGD) or T1a tumors ≤2 cm; ablation alone is a primary treatment option for patients with HGD
  • Select pT1a or pT1b tumors can be treated with endoscopic resection (ER); ablation of residual Barrett esophagus should follow ER
  • Additional ablation may be needed after ER if multifocal HGD is present elsewhere in the esophagus but may not be needed for tumors that are completely resected
  • Esophagectomy is indicated for patients with extensive HGD or pT1a adenocarcinoma with nodular disease that is not adequately controlled by ER with or without ablation; a transhiatal or transthoracic, or minimally invasive approach may be used; gastric reconstruction preferred; for postoperative nutritional support, feeding jejunostomy is preferred to gastrostomy
  • Primary treatment options for patients with squamous cell carcinoma T1b, N+ tumors and locally advanced resectable tumors (T2-T4a, any regional N) include preoperative chemoradiation (for non-cervical esophagus tumors), definitive chemoradiation (recommended for cervical esophagus tumors) or esophagectomy (for non-cervical esophagus tumors)
  • For patients with adenocarcinoma T1b, N+ tumors and locally advanced resectable tumors (T2-T4a, any regional N) preoperative chemoradiation is preferred; definitive chemoradiation is indicated only for non-surgical patients; esophagectomy is an option for patients with low-risk, <2 cm, well-differentiated lesions
  • Tumors in the submucosa (T1b) or deeper may be treated with esophagectomy
  • For patients with squamous cell carcinoma, no postoperative treatment is indicated if there is no residual disease at surgical margins (R0 resection)
  • For patients with adenocarcinoma who have not received preoperative therapy, postoperative fluoropyrimidine-based chemoradiation (following R0 resection) is indicated for all patients with Tis, T3-T4 tumors, node-positive T1-T2 tumors, and selected patients with T2, N0 tumors with high-risk features
  • Chemotherapy following R0 resection is indicated for all patients with adenocarcinoma, irrespective of the nodal status
  • Chemoradiation may be offered to all patients with residual disease at surgical margins (R1 and R2 resections)
  • Definitive chemoradiation is preferred for all T4b (unresectable) tumors
  • Fluoropyrimidine- or taxane-based regimens are indicated for preoperative and definitive chemoradiation

The 2013 American Society for Gastrointestinal Endoscopy (ASGE) guidelines note that argon plasma coagulation (APC), heater probe, cryotherapy, or radiofrequency ablation should not be used as monotherapy with curative intent for T1a tumors. However, those techniques may have a role in ablation of remaining high-risk tissue following resection. [9]

In 2014, the Society of Thoracic Surgeons (STS) released clinical practice guidelines for multimodal treatment of esophageal cancer with the following recommendations [10] :

  • Locally advanced disease should be treated in a multidisciplinary setting
  • Restaging should be performed after neoadjuvant therapy and before surgery
  • Endoscopic ultrasound restaging for residual local disease is inaccurate and can be omitted
  • A PET scan should be used for restaging after neoadjuvant therapy to detect interval development of distant metastatic disease
  • Neoadjuvant chemoradiation therapy should be used for locally advanced squamous cell cancer and either neoadjuvant chemotherapy or chemoradiation therapy for locally advanced adenocarcinoma; multimodality therapy has advantages over surgical resection alone
  • For patients with adenocarcinoma who have not received neoadjuvant therapy, adjuvant chemoradiotherapy is an option for regional lymph node disease.
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Metastatic Disease and Palliative Care

NCCN guidelines recommend the following for treatment of metastatic or recurrent disease [1] :

  • Recurrence after esophagectomy can be treated with fluoropyrimidine-based or taxane-based concurrent chemoradiation in patients who did not receive prior chemoradiation
  • Selected patients with recurrences can undergo repeat resection
  • Recurrence after chemoradiation without esophagectomy in medically fit patients with resectable tumors, can be treated with esophagectomy
  • Palliative care is indicated for medically unfit patients, or those with unresectable or metastatic recurrence
  • First-line therapy with two-drug chemotherapy regimens is preferred for advanced or metastatic disease
  • Docetaxel and irinotecan are options for second-line therapy for locally advanced or metastatic disease

The 2013 American Society for Gastrointestinal Endoscopy (ASGE) guidelines recommend the following for palliative care [9] :

  • Esophageal stent placement is the preferred method for palliation of dysphagia and fistulae
  • Patient preferences, quality of life, and prognosis should be addressed with the patient and family before initiating endoscopic palliation
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