Esophageal Cancer Treatment & Management

Updated: Apr 20, 2021
  • Author: Muhammad Masab, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Approach Considerations

Treatment of esophageal cancer varies according to stage—locoregional (stages I-III) versus metastatic cancer (stage IV)—and  histologic subtype—squamous cell carcinoma (SCC) versus adenocarcinoma.

National Comprehensive Cancer Network (NCCN) treatment recommendations for esophageal cancer include the following [83] :

  • 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 SCC 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 SCC, no postoperative treatment is indicated if no residual disease is present 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.
  • Two-drug cytotoxic regimens are preferred for patients with advanced disease because of lower toxicity.
  • Trastuzumab should be added to first-line chemotherapy (category 1 for combination with cisplatin and fluoropyrimidine; category 2B for combination with other chemotherapy agents) for patients with HER2-overexpressing advanced or metastatic adenocarcinoma (a tumor immunohistochemistry [IHC] score of  3+ or 2+ with the evidence of HER2 amplification by fluorescent in situ hybridization [FISH]). [84]
  • Ramucirumab, either as a single agent or in combination with paclitaxel, was approved in 2014 by the US Food and Drug Administration (FDA) for the treatment of patients with advanced esophagogastric junction (EGJ) adenocarcinoma refractory to or progressive following first-line therapy with platinum- or fluoropyrimidine-based chemotherapy.

Surgical Indications and Contraindications

Surgery remains the cornerstone of treatment for esophageal cancer. Indications for surgery include the following:

  • Esophageal cancer in a patient who is a candidate for surgery

  • High-grade dysplasia in a patient with Barrett esophagus that cannot be adequately treated endoscopically [2, 3]

Contraindications to surgery include the following:

  • Metastasis to N2 nodes (ie, cervical or supraclavicular lymph nodes) or solid organs (eg, liver, lungs); the treatment of patients with celiac lymph node involvement remains controversial [85]

  • Invasion of adjacent structures (eg, the recurrent laryngeal nerve, tracheobronchial tree, aorta, pericardium)

In addition, the presence of severe, associated comorbid conditions (eg, cardiovascular disease, respiratory disease) can decrease a patient's chances of surviving an esophageal resection. Consequently, cardiac and respiratory function must be carefully evaluated preoperatively. A forced expiratory volume in 1 second of less than 1.2 L and a left ventricular ejection fraction of less than 0.4 are relative contraindications to the operation.



Esophageal resection (esophagectomy) remains a critical component of multimodality therapy for patients with tumors of any stage. Endoscopic mucosal resection is an experimental approach to patients with T1a disease or high-grade dysplasia that is limited to certain centers and performed only under protocol. Esophagectomy is no longer is used for palliation of symptoms because other treatment modalities have become available for relieving dysphagia.

An esophagectomy can be performed by using an abdominal and a cervical incision with blunt mediastinal dissection through the esophageal hiatus (ie, transhiatal esophagectomy [THE]) or by using an abdominal and a right thoracic incision (ie, transthoracic esophagectomy [TTE]).

THE offers the advantage of avoiding a chest incision, which can cause prolonged discomfort and can further aggravate the condition of patients with compromised respiratory function. After removal of the esophagus, continuity of the gastrointestinal tract is usually reestablished using the stomach.

Some authors have questioned the validity of THE as a cancer operation because part of the operation is not performed under direct vision and fewer lymph nodes are removed than with TTE. However, many retrospective studies and 2 prospective ones have shown no difference in survival between the operations, suggesting that the factor influencing survival is not the type of operation but, rather, the stage of the cancer at the time the operation is performed. [62, 63, 86, 87, 88, 89]

Morbidity and mortality

Complications from esophagectomy occur in approximately 40% of patients. The morbidity associated with the surgery consists mostly of respiratory, cardiac, and septic complications, including the following:

  • Respiratory complications (15-20%) - Include atelectasis, pleural effusion, and pneumonia

  • Cardiac complications (15-20%) - Include cardiac arrhythmias and myocardial infarction

  • Septic complications (10%) - Include wound infection, anastomotic leak (breakdown of the new connection between the stomach and esophagus), and pneumonia

Anastomotic leaks and stricture may require dilatation (20%). Leaks may be treated with endoscopic placement of self-expanding, removable plastic stents. [90]

Leak rates vary depending on whether the anastomosis is in the chest (3%-12%) or the neck (10%-25%). [91] The choice of location for the anastomosis is based mostly on the location of the tumor and the surgeon’s assessment of the risks and benefits of a thoracic anastomosis. Such anastomoses have a lower leak rate, but an intrathoracic leak following esophagectomy can lead to sepsis and death.

A retrospective review of 1223 esophagectomies for cancer found that surgical management of intrathoracic leaks did not increase the patient mortality rate or effect long-term survival. [91]

As with other complex operations (eg, cardiac operations, resection of the pancreas or liver), the lowest mortality rate with esophagectomy is achieved when the procedure is performed in high-volume centers by high-volume surgeons. In California from 1990-1994, for instance, 5 high-volume centers had a mortality rate of 5% or less for esophageal resection for cancer, while the state’s average mortality rate for this surgery was approximately 18%. [92]

The better results in high-volume centers are due to a team approach. In these facilities, expert surgeons work with intensivists, cardiologists, pulmonologists, radiologists, and nurses who have experience and expertise.

Transthoracic esophagectomy

There are two types of TTE, as follows:

  • Ivor Lewis esophagectomy (right thoracotomy and laparotomy)
  • McKeown esophagectomy (right thoracotomy followed by laparotomy and cervical anastomosis) 

For TTE, the patient is placed supine on the operating room table. An arterial line, a central venous catheter, a Foley catheter, and a dual-lumen endotracheal tube are placed. Preoperative antibiotics are administered. An upper midline incision is made.

After exploring the peritoneal cavity for metastatic disease (if metastases are found, the operation is not continued), the stomach is mobilized. The right gastric and the right gastroepiploic arteries are preserved, while the short gastric vessels and the left gastric artery are divided.

Next, the gastroesophageal junction is mobilized, and the esophageal hiatus is enlarged. A pyloromyotomy is performed, and a feeding jejunostomy is placed for postoperative nutritional support.

After closure of the abdominal incision, the patient is repositioned in the left lateral decubitus position and a right posterolateral thoracotomy is performed in the fifth intercostal space.

The azygos vein is divided to allow full mobilization of the esophagus. The stomach is delivered into the chest through the hiatus and is then divided approximately 5 cm below the gastroesophageal junction.

An anastomosis (hand-sewn or stapled) is performed between the esophagus and the stomach at the apex of the right chest cavity. Then, the chest incision is closed.

McKeown esophagectomy, with an anastomosis in the cervical region, is similar in conduct, but with the advantage of being applicable for tumors in the upper, middle, and lower thoracic esophagus.

Transhiatal esophagectomy

For THE, the preoperative details are similar to those of TTE, except that a single-lumen, rather than a double-lumen, endotracheal tube is used. The neck is prepared in the operative field.

The abdominal part of the operation is identical to the TTE; however, dissection of the esophagus is performed through the enlarged esophageal hiatus without opening the right chest. The esophagus is mobilized in this fashion all the way to the thoracic inlet.

Then, a 6-cm incision is made in the left side of the neck. The internal jugular vein and carotid artery are retracted laterally, and the esophagus is identified and isolated posterior to the airway. To prevent injury to the left recurrent laryngeal nerve, no mechanical retractors are used to retract the trachea.

Next, after resection of the proximal stomach and thoracic esophagus, the remaining stomach is pulled up through the posterior mediastinum until it reaches the remaining esophagus at the cervical level. Then, a hand-sewn anastomosis is performed, and a small drain is placed in the neck alongside the anastomosis. The abdominal and neck incisions are closed. (See the image below.)

Esophageal cancer. Transhiatal esophagectomy in wh Esophageal cancer. Transhiatal esophagectomy in which (a) is the abdominal incision, (b) is the cervical incision, and (c) is the stomach stretching from abdomen to the neck.

Minimally invasive esophagectomy

The use of laparoscopic and thoracoscopic techniques has revolutionized the treatment of benign esophageal disorders such as achalasia and gastroesophageal reflux disease (GERD). Advantages of minimally invasive surgery include a shorter hospital stay, less postoperative discomfort, and much faster recovery time than with open surgery. Minimally invasive esophagectomy (MIE) is finding a place in the treatment of esophageal cancer. [93]

In a study of MIE (mainly using thoracoscopic mobilization) in 222 patients, the mortality rate was only 1.4% and hospital stay was only 7 days, which is less than with most open procedures; only 16 patients (7.2%) required conversion to an open procedure. [94] A report by Luketich et al involving 56 patients also showed that MIE was comparable to open esophagectomy but the use of neoadjuvant treatment slightly increased the surgical mortality from 1.5% to 1.8%. [94]

In a randomized French study that compared transthoracic open esophagectomy (n=104) with MIE (hybrid procedure; n=103), .Mariette et al reported that the incidence of intraoperative and postoperative major complications, specifically pulmonary complications, was 69% lower with the hybrid procedure, while 3- and 5-year overall survival and disease-free survival were noninferior. For the hybrid procedure, the abdominal portion of the operation was performed through five small incisions, rather than the long abdominal incision used in TTE. [95, 96]

Video-assisted thoracoscopy (VATS) is being used in many centers for the thoracic mobilization of the esophagus, reducing the size of the chest incision. In addition, laparoscopy can be used to mobilize the gastric conduit in the abdomen, reducing abdominal incision size as well.

A study by Uenosono et al found that sentinel node mapping can be applied to patients with clinical T1 and N0 esophageal cancer. Use of this technique may facilitate less invasive surgery, with reduction of lymphadenectomy. [97]

Endoscopic mucosal resection (EMR) is a modern, attractive option for the treatment of superficial esophageal cancers. High-grade dysplasia and mucosa-limited neoplasms are candidates for EMR, because of the low risk of node metastasis in these cases. A population-based study of 1618 patients with grade Tis, T1a, or T1b esophageal cancer found that overall survival times and esophageal-cancer-specific survival times with endoscopic therapy were similar to those with surgery, after adjustment for patient and tumor factors. [98, 99]

Salvage endoscopic resection

In patients with local failure after definitive chemoradiotherapy (CRT) for esophageal squamous cell carcinoma (SCC), salvage endoscopic treatment (SET) may be a viable option, according to a study reported at the 2014 Gastrointestinal Cancers Symposium. [100] The study included 716 esophageal SCC patients treated with CRT, 417 of whom experienced local failure (incomplete response or local recurrence); of these 417 patients, 164 underwent SET (either photodynamic therapy or endoscopic resection).

Curative resection was achieved in 88% of the patients who underwent endoscopic resection, and a complete response was achieved in 57.5% of those who underwent photodynamic therapy. [100] Overall survival and relapse-free survival rates at 5 years were 38.6% and 28%, respectively. The factors most strongly predictive of improved survival were (1) an absence of lymph node metastasis before CRT and (2) an elapsed time of 6 months or longer between the initiation of CRT and the performance of SET. [100]


Chemotherapy and Radiotherapy

Chemotherapy and radiotherapy for esophageal cancer are delivered preoperatively. No survival benefit is obtained when radiation and chemotherapy are administered postoperatively; however, postoperative continuance of chemotherapy started preoperatively may be beneficial. [101] The aims of preoperative (neoadjuvant) chemotherapy and radiotherapy are to reduce the bulk of the primary tumor before surgery to facilitate higher curative resection rates and to eliminate or delay the appearance of distant metastases.

Most chemotherapy that is currently used for the treatment of esophageal cancer, including alkylating, antimetabolite, anthracycline, and antimicrotubular agents, are not approved for this indication by the US Food and Drug Administration (FDA). Chemotherapy for squamous cell esophageal carcinoma, as with squamous cell carcinomas in general, is based on cisplatin, while chemotherapy for esophageal adenocarcinoma has been extrapolated from experience in patients with adenocarcinoma of the stomach.

Neoadjuvant chemotherapy alone appears to offer a limited benefit at best. A North American randomized trial found that preoperative chemotherapy with a combination of cisplatin and fluorouracil did not improve overall survival among patients with squamous cell cancer or adenocarcinoma of the esophagus. In a larger trial, British investigators found that preoperative chemotherapy with those 2 agents resulted in a 5-year survival rate of 23.0%, compared with 17.1% for surgery alone. [102]

In contrast, the Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) demonstrated considerable benefit from preoperative chemoradiation over surgery alone in selected patients with esophageal or esophagogastric junction cancer (tumor stage T1N1 or T2–T3 with any N). [103] Median overall survival with chemoradiation therapy followed by surgery was 49.4 months, compared with 24.0 months with surgery alone.

An analysis of data from CROSS I and II showed that preoperative chemoradiotherapy (CRT) plus surgery was superior to surgery alone in preventing local, regional, and distant recurrence, particularly hematogenous metastasis and peritoneal carcinomatosis. [104, 105, 106] Overall recurrence rates were 35% for CRT plus surgery and 58% for surgery alone. The rates of locoregional recurrence, peritoneal carcinomatosis, and hematogenous dissemination were all lower for the former as well (14% vs 34%, 4% vs 14%, and 29% vs 35%, respectively).

Neoadjuvant therapy consists of a combination of radiotherapy (approximately 45 Gy) and chemotherapy with cisplatin and 5-fluorouracil. While the radiotherapy acts locally at the tumor site, the chemotherapy acts on tumor cells that have already spread. This combination therapy is usually administered over a 45-day period; esophageal resection is performed after an interval of approximately 4 weeks.

In a study of patients with distal esophageal carcinoma, Franko and colleagues reported that a longer interval between neoadjuvant chemoradiation and esophagectomy was significantly associated with worse outcomes. The median interval between radiation therapy and esophagectomy was 7.1 weeks; when the delay was 9 weeks or more, perioperative mortality was increased and overall survival decreased. [107]

Rohatgi et al reported that the response to preoperative chemoradiotherapy correlated strongly with overall survival and disease-free survival in patients with esophageal cancer. In their review of 235 cases, survival decreased progressively between patients who achieved a pathologic complete response, those who had a partial response (1-50% residual carcinoma in the resected specimen), and those with no response (greater than 50% residual carcinoma). [108]

A study by Rao et al identified groups of esophageal tumors with distinct gene expression profiles, which in future may allow for tailored treatment protocols. [109] Similarly, Alexander et al identified DNA-repair biomarkers that predict response to neoadjuvant chemotherapy. [110]

A trial involving 111 patients undergoing chemoradiotherapy for head-and-neck or esophageal cancer indicated that enteral nutrition enriched with n-3 fatty acids helps to preserve body mass and improve nutritional and functional status parameters during chemoradiotherapy. [111, 112]


In July 2019, the FDA approved pembrolizumab (Keytruda) for patients with recurrent, locally advanced or metastatic, squamous cell carcinoma of the esophagus (ESCC) whose tumors express programmed death ligand 1 (PD-L1) with a Combined Positive Score (CPS) ≥10, as determined by an FDA-approved test, with disease progression after 1 or more prior lines of systemic therapy. [113]

Efficacy was observed in two clinical trials, KEYNOTE‑181 and KEYNOTE‑180. KEYNOTE-181 (n=628) was a phase 3 randomized, open-label, active-controlled trial that enrolled patients with recurrent locally advanced or metastatic esophageal cancer that had progressed on or after one prior line of systemic treatment for advanced or metastatic disease. Patients were randomized to receive either pembrolizumab or the investigator’s choice of a paclitaxel, docetaxel, or irinotecan regimen as a control arm. In patients with PD-L1 CPS ≥10, the median overall survival was 9.3 months and 6.7 months in the pembrolizumab and control arms, respectively. [114]

KEYNOTE‑180 was a single arm, open-label trial that enrolled patients with locally advanced or metastatic esophageal cancer who progressed on or after at least 2 prior systemic treatments for advanced disease. In the patients with ESCC expressing PD-L1 CPS ≥10, ORR was 20% and response durations ranged from 4.2 to 25.1+ months, with 71% having responses of 6 months or longer and 57% having responses of 12 months or longer. [115]

On May 2021, the FDA granted accelerated approval to pembrolizumab in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma.

Approval was based on the KEYNOTE-811 trial, a multicenter, randomized, double-blind, placebo-controlled trial in patients with HER2-positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for metastatic disease. The overall response rate was 74% (95% CI 66, 82) in the pembrolizumab arm and 52% (95% CI 43, 61) in the placebo arm. The median duration of response was 10.6 months for the pembrolizumab arm and 9.5 months for the placebo arm. [178]


The FDA approved tipiracil/trifluridine in 2019 for metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma previously treated with at least 2 prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.

Approval of tipiracil/trifluridine was based on the phase 3 TAGS (TAS-102 Gastric Study) clinical trial (n=507). Patients in the tipiracil/trifluridine group had a median overall survival 5.7 months compared with 3.6 months in the placebo group (one-sided P=0·00029, two-sided P=0·00058). [116]


The FDA approved nivolumab in April 2021 for first-line immunotherapy in combination with fluoropyrimidine- and platinum-containing chemotherapy for advanced or metastatic esophageal adenocarcinoma and gastroesophageal junction (GEJ) cancer, as well as for gastric cancer. In the phase 3 CheckMate 649 trial, which involved 1581 previously untreated patients with unresectable HER2-negative gastric cancer, GEJ cancer, or esophageal adenocarcinoma, 60% of which had a PD-L1 CPS ≥5, nivolumab plus oxaliplatin-based chemotherapy was associated with significantly better overall survival (OS) than chemotherapy alone (13.8 months vs 11.6 months, respectively; P = 0.0002). In patients with a PD-L1 CPS ≥5, progression-free survival (PFS) was also significantly improved with nivolumab plus chemotherapy (median 7.7 months vs 6.0 months, P < 0.0001). [117, 118]

In contrast, the phase 3 ATTRACTION-4 study, conducted in Japan, Korea, and Taiwan, which involved involved 724 previously untreated patients with HER2-negative gastric or GEJ cancer, nivolumab plus chemotherapy did not significantly improve OS but did significantly improve PFS, at a median 10.5 months vs 8.3 months with chemotherapy alone (P = 0.0007). [117]

Despite these findings, the FDA approved nivolumab for completely resected esophageal or GEJ cancer in patients with residual pathologic disease who have received neoadjuvant chemoradiotherapy.

Approval was based on the randomized, double-blind trial, CHECKMATE-577, where 794 patients with completely resected esophageal or GEJ cancers who had residual pathologic disease following concurrent chemoradiotherapy. A statistically significant improvement in disease-free survival (DFS) was demonstrated in the nivolumab arms (22.4 months [95% CI: 16.6, 34.0]) compared to the placebo arm (11 months [95% CI: 8.3, 14.3]). The DFS benefit was observed regardless of tumor PD-L1 expression and histology. [179]


Palliative Care

In patients who are not candidates for surgery, because of their clinical condition or advanced disease, treatment focuses on control of dysphagia. The goal of palliative care is to prevent and relieve suffering and improve quality of life for patients and their caregivers regardless of the disease stage. In patients with unresectable or locally advanced cancer, palliative interventions provide symptomatic relief and may result in significant prolongation of life, improvement in nutritional status, the sensation of well-being, and overall quality of life.

Although various treatment options are available for the management of dysphagia, optimal treatment is still debated. A multimodality interdisciplinary approach is strongly encouraged.

Dysphagia is the most common symptom in patients with esophageal cancer. Assessing the severity of the condition and swallowing impairment is essential to initiate appropriate interventions for long-term palliation of dysphagia in patients with esophageal cancer.

Available palliative methods for the management of dysphagia include the following:

  • Endoscopic lumen restoration or enhancement
  • Temporary self-expanding metal stents (SEMS)
  • External beam radiation therapy (EBRT) 
  • Brachytherapy
  • Chemotherapy
  • Laser
  • Surgery

National Comprehensive Cancer Network guidelines for best supportive/palliative care

For patients with complete esophageal obstruction, the NCCN guidelines [83] recommend the following:

  • Endoscopic lumen restoration
  • EBRT
  • Chemotherapy
  • Surgery

Surgical or radiologic placement of jejunostomy or gastronomy tubes may be necessary to provide adequate hydration and nutrition, if endoscopic lumen restoration is not undertaken or is unsuccessful. Brachytherapy may be considered instead of EBRT if lumen can be restored using appropriate applicators during the delivery of brachytherapy to avoid an excessive dose on mucosal surfaces. In a multicenter randomized trial, single-dose brachytherapy was associated with fewer complications and better long-term relief of dysphagia compared with metal stents. [119]  

For patients with severe esophageal obstruction (those able to swallow liquids only), some additional options include endoscopic lumen enhancement (wire-guided or balloon dilation) and endoscopy or fluoroscopy-guided placement of covered expandable metal stents. While some data suggest a lower migration and re-obstruction rate with the larger-diameter covered expandable metal stents, there may be a higher risk of stent-related complications [120]  


Long-term palliation of dysphagia can be achieved with endoscopic, radiographic-assisted insertion of expandable metal or plastic stents. [121, 122] Temporary placement of self-expanding metal stents (SEMS) with concurrent EBRT was found to increase survival rates compared with permanent stent placement. [123] SEMS is the preferred treatment for patients with tracheoesophageal fistula and those who are not candidates for chemoradiation or who failed to achieve adequate palliation with such therapy. [124] Membrane-covered stents have significantly better palliation than conventional bare metal stents because of a lower rate of tumor ingrowth. [122]


Radiation therapy is successful in relieving dysphagia in approximately 50% of patients. In patients with advanced esophageal cancer, the preoperative combination of chemotherapy and radiotherapy has shown good results.

In a large, multicenter study, Herskovic and colleagues reported a 2-year survival rate of 38%, with a median survival period of 12.5 months, for patients treated with radiotherapy in combination with chemotherapy (fluorouracil and cisplatin), compared with a 2-year-survival rate of 10% and a median survival period of 8.5 months in patients treated with radiotherapy alone. [125, 126]

Folkert et al found that high-dose-rate (HDR) endoluminal brachytherapy was well tolerated in medically inoperable patients with superficial primary or recurrent esophageal cancer. Over the course of 3 years, 14 patients were treated with HDR intraluminal brachytherapy; 10 had recurrent esophageal cancer and 4 had previously unirradiated lesions. The overall freedom from failure (OFFF) and the overall survival (OS) rate at 18 months were 30.8% and 72.7%, respectively. Patients with recurrent disease had an 11.1% OFFF and a 55.6% OS rate at 18 months. For patients with previously unirradiated disease, the OFFF was 75% and the OS rate was 100%. [127]


Chemotherapy as a single modality has limited use. Only a few patients achieve a modest and short-lived response.

A phase 3 study from the United Kingdom suggests that docetaxel may be useful as a second-line treatment for patients with esophageal cancer who have progressed after first-line chemotherapy. [128, 129] Median overall survival was significantly better in patients treated with docetaxel than in those managed with active symptom control (5.2 versus 3.6 months, respectively).

Because survival in these patients is measured in months, quality of life is an important consideration. In the UK study, quality-of-life questionnaires demonstrated no differences between the 2 groups on global and functioning scores but did indicate an improvement in symptom scores, with the docetaxel group reporting less pain. [128, 129]

In 2006, a Cochrane review tried to assess the effectiveness of chemotherapy versus best supportive care, as well as that of different chemotherapy regimens against each other, in metastatic esophageal carcinoma. The authors found that no consistent benefit with any specific chemotherapy regimen. [130] Cisplatin, 5-fluorouracil (5-FU), paclitaxel, and anthracyclines had promising response rates and tolerable toxicity.

Laser therapy

Laser therapy (Nd:YAG laser) can help to achieve temporary relief of dysphagia in as many as 70% of patients. Multiple sessions are usually required to keep the esophageal lumen patent.

The photosensitizer porfimer (Photofrin) is FDA approved for palliation of patients with completely obstructing esophageal cancer or partially obstructing cancer that cannot be satisfactorily treated with Nd:YAG laser therapy. Intravenous injection of porfimer is followed 40–50 hours later with delivery of 630 nm wavelength laser light; a second laser light treatment may be given 96–120 hours after the injection. Photodynamic therapy (PDT) with porfimer sodium has overall equal efficacy to Nd:YAG laser thermal ablation for palliation of dysphagia in esophageal cancer, and equal or better objective tumor response rate. Temporary photosensitivity is a limitation, but PDT is carried out with greater ease and is associated with fewer acute perforations than Nd:YAG laser therapy [121] .


Postoperative Care and Follow-up

The average length of postoperative hospital stay for patients with esophageal cancer is 9-14 days. Patients usually spend the first postoperative night in the intensive care unit (ICU).

Patients can be extubated immediately after the operation, but mechanical ventilation should be continued if any concerns about the respiratory status are present. Respiratory complications (eg, atelectasis, pleural effusion, pneumonia) and cardiac complications (eg, cardiac arrhythmias) usually occur in the first postoperative days. Patients leave the ICU and are transferred to the surgical ward only when their respiratory status and cardiac status are satisfactory.

Feeding through the feeding jejunostomy begins on postoperative day 1. On postoperative day 6, a swallow study is performed to check for anastomotic leakage. If no leak is present, patients start oral feedings. If a leak is present, the drainage tubes are left in place and nutrition is provided entirely through the feeding jejunostomy until the leak closes spontaneously.

Approximately 85%-90% of patients go home after discharge. The remaining patients may need additional time in a skilled nursing facility if they live alone and if they cannot take care of themselves.

Patients are seen by the responsible surgeon at 2 weeks and 4 weeks after discharge from the hospital and subsequently every 6 months by an oncologist. Most patients return to their regular level of activities within 2 months.


Prevention of Esophageal Cancer

For squamous cell carcinoma, prevention consists of smoking cessation, efforts to reduce alcohol abuse, and consumption of a diet containing an adequate amount of fruits, vegetables, and vitamins. Both the National Comprehensive Cancer Network (NCCN) guidelines and the National Cancer Institute (NCI) cancer information summary for esophageal cancer prevention conclude that smoking cessation decreases the risk of squamous cell carcinoma. [83, 131]

For esophageal adenocarcinoma, prevention involves stopping the sequence of events leading from gastroesophageal reflux disease (GERD) to Barrett esophagus to adenocarcinoma. Better control of gastroesophageal reflux can prevent the development of Barrett metaplasia in patients with GERD and can discourage the development of high-grade dysplasia in patients with metaplasia. Endoscopic follow-up evaluations should be performed at 1- to 2-year interval to detect the presence of dysplasia, allowing intervention before cancer develops

Hereditary Cancer Predisposition Syndromes Associated with an Increased Risk for Esophageal and EGJ Cancers

Surveillance upper endoscopy with biopsy (see the table below) should be considered for patients who have one of the following hereditary cancer predisposition syndromes:

  • Tylosis (non-epidermolytic palmoplantar keratosis [PPK] or Howel Evans Syndrome)
  • Familial Barrett esophagus (FBE)
  • Bloom syndrome
  • Fanconi anemia (FA)

Table 5. Hereditary Cancer Predisposition Syndromes Associated with an Increased Risk for Esophageal Cancers. (Open Table in a new window)

Syndrome Gene(s) Inheritance Pattern Clinical Manifestation Surveillance Recommendations
Tylosis (non-Epidermolytic palmoplantar keratosis (PPK) or Howel Evans syndrome) RHBDF2 Autosomal dominant Skin thickening of palms and soles. Non-epidermolytic PPK is associated with high risk of developing SCC of esophagus (40-90% by age of 70 years) [41, 38] Surveillance by upper GI endoscopy is recommended for family members with tylosis after 20 years of age [41]
Familial Barrett esophagus (FBE) Genes not identified  Autosomal dominant Familial aggregation of Barrett esophagus, adenocarcinoma of the esophagus and EGJ [132, 133] Potential family history of Barrett esophagus, and adenocarcinoma of the esophagus,should be determined for patients presenting with GERD, especially white men older than 40 years of age.
Bloom syndrome BLM/RECQL3 Autosomal recessive  Increased predisposition to a wide variety of malignancies [134] . Acute myeloid leukemia, acute lymphoblastic leukemia, lymphoid neoplasms, and Wilms tumor are the predominant cancers diagnosed before 25 years of age, whereas carcinomas of different anatomic sites including SCC of the esophagus are diagnosed after 20 years of age. Chromosomal quadraradials with breakage may be used for the diagnosis of BS  [41] Screening for GERD with or without endoscopy after 20 years of age may be considered to detect cancer early. 
Fanconi anemia (FA) FANC [135] Autosomal recessive  Characterized by congenital malformations, progressive pancytopenia, easy bruising, chromosomal breakage and an increased predisposition to the development of hematologic malignancies as well as solid tumors [41] . AML is the most common cancer type in patients with FA. However, patients with FA are also at an increased risk of developing SCC of head, neck and esophagus, cervical cancer, and brain tumors. [41, 136, 137] Enhanced mitomycin C–induced chromosomal breakage analysis can help in diagnosis. [138]

Endoscopy of the esophagus may be considered as a surveillance strategy in individuals identified with FA.