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The esophagus is the hollow, muscular tube that moves food and liquid from the throat to the stomach. The wall of the esophagus is made up of several layers of tissue, including mucous membrane, muscle, and connective tissue. Esophageal cancer starts at the inside lining of the esophagus and spreads outward through the other layers as it grows.
The two most common forms of esophageal cancer are named for the type of cells that become malignant (cancerous):
Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn't mean that you will not get cancer. Talk with your doctor if you think you may be at risk. Risk factors include the following:
These and other signs and symptoms may be caused by esophageal cancer or by other conditions. Check with your doctor if you have any of the following:
The following tests and procedures may be used:
The prognosis (chance of recovery) and treatment options depend on the following:
When esophageal cancer is found very early, there is a better chance of recovery. Esophageal cancer is often in an advanced stage when it is diagnosed. At later stages, esophageal cancer can be treated but rarely can be cured. Taking part in one of the clinical trials being done to improve treatment should be considered. Information about ongoing clinical trials is available from the NCI Web site.
The process used to find out if cancercells have spread within the esophagus or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The following tests and procedures may be used in the staging process:
Cancer can spread through tissue, the lymph system, and the blood:
When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.
The metastatic tumor is the same type of cancer as the primary tumor. For example, if esophageal cancer spreads to the lung, the cancer cells in the lung are actually esophageal cancer cells. The disease is metastatic esophageal cancer, not lung cancer.
In stage 0, abnormalcells are found in the inner (mucosal) layer of the esophageal wall. These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is also called high-gradedysplasia.
Stage I is divided into Stage IA and Stage IB, depending on where the cancer is found.
Stage II is divided into Stage IIA and Stage IIB, depending on where the cancer has spread.
Stage III is divided into Stage IIIA, Stage IIIB, and Stage IIIC, depending on where the cancer has spread.
In Stage IV, cancer has spread to other parts of the body.
Recurrentesophageal cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the esophagus or in other parts of the body.
Different types of treatment are available for patients with esophageal cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.
Many people with esophageal cancer find it hard to eat because they have trouble swallowing. The esophagus may be narrowed by the tumor or as a side effect of treatment. Some patients may receive nutrients directly into a vein. Others may need a feeding tube (a flexible plastic tube that is passed through the nose or mouth into the stomach) until they are able to eat on their own.
Surgery is the most common treatment for cancer of the esophagus. Part of the esophagus may be removed in an operation called an esophagectomy.
The doctor will connect the remaining healthy part of the esophagus to the stomach so the patient can still swallow. A plastic tube or part of the intestine may be used to make the connection. Lymph nodes near the esophagus may also be removed and viewed under a microscope to see if they contain cancer. If the esophagus is partly blocked by the tumor, an expandable metal stent (tube) may be placed inside the esophagus to help keep it open.
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.
A plastic tube may be inserted into the esophagus to keep it open during radiation therapy. This is called intraluminal intubation and dilation.
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.
Chemoradiation therapy combines chemotherapy and radiation therapy to increase the effects of both.
Laser therapy is a cancer treatment that uses a laser beam (a narrow beam of intense light) to kill cancer cells.
Electrocoagulation is the use of an electric current to kill cancer cells.
Information about clinical trials is available from the NCI Web site.
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.
Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.
Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.
Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
Treatment of stage 0 is usually surgery.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 esophageal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
Treatment of stage I esophageal squamous cell carcinoma or adenocarcinoma may include the following:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I esophageal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
Treatment of stage II esophageal squamous cell carcinoma or adenocarcinoma may include the following:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II esophageal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
Treatment of stage III esophageal squamous cell carcinoma or adenocarcinoma may include the following:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III esophageal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
Treatment of stage IV esophageal squamous cell carcinoma or adenocarcinoma may include the following:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV esophageal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
Treatment of recurrentesophageal cancer may include the following:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent esophageal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
For more information from the National Cancer Institute about esophageal cancer, see the following:
For general cancer information and other resources from the National Cancer Institute, see the following:
This information is provided by the National Cancer Institute.
This information was last updated on June 16, 2014.
Estimated new cases and deaths from esophageal cancer in the United States in 2014:
The incidence of esophageal cancer has risen in recent decades, coinciding with
a shift in histologic type and primary tumor location. Adenocarcinoma of
the esophagus is now more prevalent than squamous cell carcinoma in the United
States and western Europe, with most tumors located in the distal esophagus.
The cause for the rising incidence and demographic alterations is unknown.
While risk factors for squamous cell carcinoma of the esophagus have been
identified (e.g., tobacco, alcohol, diet), the risk factors associated with
esophageal adenocarcinoma are less clear. The presence of Barrett
esophagus is associated with an increased risk of developing adenocarcinoma of
the esophagus, and chronic reflux is considered the predominant cause of
Barrett metaplasia. The results of a population-based, case-controlled study
from Sweden strongly suggest that symptomatic gastroesophageal reflux is a risk
factor for esophageal adenocarcinoma. The frequency, severity, and duration of
reflux symptoms were positively correlated with increased risk of esophageal
Esophageal cancer is a treatable disease, but it is rarely curable. The overall
5-year survival rate in patients amenable to definitive treatment ranges from 5% to 30%.
The occasional patient with very early disease has a better chance of survival.
Patients with severe dysplasia in distal esophageal Barrett mucosa often have in situ or even invasive cancer within the dysplastic area. Following
resection, these patients usually have excellent prognoses.
Primary treatment modalities include surgery alone or chemotherapy with
radiation therapy. Combined modality therapy (i.e., chemotherapy plus surgery, or
chemotherapy and radiation therapy plus surgery) is under clinical evaluation.
Effective palliation may be obtained in individual cases with various
combinations of surgery, chemotherapy, radiation therapy, stents,
photodynamic therapy, and endoscopic therapy with Nd:YAG laser.
One of the major difficulties in allocating and comparing treatment modalities
for patients with esophageal cancer is the lack of precise preoperative
staging. Standard noninvasive staging modalities include computed tomography
(CT) of the chest and abdomen and endoscopic ultrasound (EUS). The overall
tumor depth staging accuracy of EUS is 85% to 90%, as compared with 50% to 80%
for CT; the accuracy of regional nodal staging is 70% to 80% for EUS and 50% to
70% for CT. EUS-guided fine-needle aspiration (FNA) for lymph node
staging is under prospective evaluation; one retrospective series reported a
93% sensitivity and 100% specificity of regional nodal staging with EUS-FNA. Thoracoscopy and
laparoscopy have been used in esophageal cancer staging at some surgical
centers. An intergroup trial reported an increase in positive lymph node detection to 56% of 107 evaluable patients using thoracoscopy/laparoscopy, from 41% (using noninvasive staging tests, e.g., CT, magnetic resonance imaging, EUS) with no major complications or deaths. Noninvasive positron emission tomography using the
radiolabeled glucose analog 18-F-fluorodeoxy-D-glucose for preoperative
staging of esophageal cancer is under clinical evaluation and may be useful in
detecting stage IV disease.
Gastrointestinal stromal tumors can occur in the esophagus and are usually
benign. (Refer to the PDQ summary on Gastrointestinal Stromal Tumors Treatment for
Other PDQ summaries containing information related to esophageal cancer include the following:
American Cancer Society: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed May 21, 2014.
Devesa SS, Blot WJ, Fraumeni JF Jr: Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 83 (10): 2049-53, 1998.
Blot WJ, McLaughlin JK: The changing epidemiology of esophageal cancer. Semin Oncol 26 (5 Suppl 15): 2-8, 1999.
Lagergren J, Bergström R, Lindgren A, et al.: Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 340 (11): 825-31, 1999.
Tietjen TG, Pasricha PJ, Kalloo AN: Management of malignant esophageal stricture with esophageal dilation and esophageal stents. Gastrointest Endosc Clin N Am 4 (4): 851-62, 1994.
Lightdale CJ, Heier SK, Marcon NE, et al.: Photodynamic therapy with porfimer sodium versus thermal ablation therapy with Nd:YAG laser for palliation of esophageal cancer: a multicenter randomized trial. Gastrointest Endosc 42 (6): 507-12, 1995.
Kubba AK: Role of photodynamic therapy in the management of gastrointestinal cancer. Digestion 60 (1): 1-10, 1999 Jan-Feb.
Heier SK, Heier LM: Tissue sensitizers. Gastrointest Endosc Clin N Am 4 (2): 327-52, 1994.
Bourke MJ, Hope RL, Chu G, et al.: Laser palliation of inoperable malignant dysphagia: initial and at death. Gastrointest Endosc 43 (1): 29-32, 1996.
Ziegler K, Sanft C, Zeitz M, et al.: Evaluation of endosonography in TN staging of oesophageal cancer. Gut 32 (1): 16-20, 1991.
Tio TL, Coene PP, den Hartog Jager FC, et al.: Preoperative TNM classification of esophageal carcinoma by endosonography. Hepatogastroenterology 37 (4): 376-81, 1990.
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 53 (7): 751-7, 2001.
Bonavina L, Incarbone R, Lattuada E, et al.: Preoperative laparoscopy in management of patients with carcinoma of the esophagus and of the esophagogastric junction. J Surg Oncol 65 (3): 171-4, 1997.
Sugarbaker DJ, Jaklitsch MT, Liptay MJ: Thoracoscopic staging and surgical therapy for esophageal cancer. Chest 107 (6 Suppl): 218S-223S, 1995.
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 114 (5): 817-21; discussion 821-3, 1997.
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 71 (4): 1073-9, 2001.
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 18 (18): 3202-10, 2000.
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 13 (3): 361-8, 2002.
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 19 (12): 3058-65, 2001.
van Westreenen HL, Westerterp M, Bossuyt PM, et al.: Systematic review of the staging performance of 18F-fluorodeoxyglucose positron emission tomography in esophageal cancer. J Clin Oncol 22 (18): 3805-12, 2004.
Fewer than 50% of esophageal cancers are squamous cell carcinomas.
Adenocarcinomas, typically arising in Barrett esophagus, account for at least
50% of malignant lesions, and the incidence of this histology appears to be
rising. Barrett esophagus contains glandular epithelium cephalad to the
Dysplasia is particularly likely to develop in the
intestinal type mucosa.
The stage determines whether the intent of the therapeutic approach will be
curative or palliative.
The AJCC has
designated staging by TNM classification to define cancer of the esophagus and esophagogastric junction.
Primary tumor cannot be assessed.
No evidence of primary tumor.
Tumor invades lamina propria, muscularis mucosae, or submucosa.
Tumor invades lamina propria or muscularis mucosae.
Tumor invades submucosa.
Tumor invades muscularis propria.
Tumor invades adventitia.
Tumor invades adjacent structures.
Resectable tumor invading pleura, pericardium, or diaphragm.
Unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etc.
aReprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103-15.
b(1) At least maximal dimension of the tumor must be recorded, and (2) multiple tumors require the T(m) suffix.
cHigh-grade dysplasia includes all noninvasive neoplastic epithelia that was formerly called carcinoma in situ, a diagnosis that is no longer used for columnar mucosae anywhere in the gastrointestinal tract.
Regional lymph nodes cannot be assessed.
No regional lymph node metastasis.
Metastases in 1–2 regional lymph nodes.
Metastases in 3–6 regional lymph nodes.
Metastases in ≥7 regional lymph nodes.
bNumber must be recorded for total number of regional nodes sampled and total number of reported nodes with metastasis.
No distant metastasis.
Squamous Cell Carcinomab
HGD = high-grade dysplasia.
bOr mixed histology, including a squamous component or not otherwise specified.
cLocation of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus.
The current staging system for esophageal cancer is based largely on
retrospective data from the Japanese Committee for Registration of Esophageal
Carcinoma. It is most applicable to patients with squamous cell carcinomas of
the upper third and middle third of the esophagus, as opposed to the increasingly
common distal esophageal and gastroesophageal junction adenocarcinomas. In
particular, the classification of involved abdominal lymph nodes as M1 disease
has been criticized. The presence of positive abdominal lymph nodes does not
appear to carry as grave a prognosis as metastases to distant organs.
Patients with regional and/or celiac axis lymphadenopathy should not
necessarily be considered to have unresectable disease caused by metastases.
Complete resection of the primary tumor and appropriate lymphadenectomy should
be attempted when possible.
Esophagus and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103-11.
Iizuka T, Isono K, Kakegawa T, et al.: Parameters linked to ten-year survival in Japan of resected esophageal carcinoma. Japanese Committee for Registration of Esophageal Carcinoma Cases. Chest 96 (5): 1005-11, 1989.
Korst RJ, Rusch VW, Venkatraman E, et al.: Proposed revision of the staging classification for esophageal cancer. J Thorac Cardiovasc Surg 115 (3): 660-69; discussion 669-70, 1998.
The prevalence of Barrett metaplasia in adenocarcinoma of the esophagus
suggests that Barrett esophagus is a premalignant condition. Strong
consideration should be given to resection in patients with high-grade
dysplasia in the setting of Barrett metaplasia. Endoscopic surveillance of
patients with Barrett metaplasia may detect adenocarcinoma at an earlier
stage more amenable to curative resection. The survival rate of patients
with esophageal cancer is poor. Asymptomatic small tumors confined to the
esophageal mucosa or submucosa are detected only by chance. Surgery is the
treatment of choice for these small tumors. Once symptoms are present
(e.g., dysphagia, in most cases), esophageal cancers have usually invaded
the muscularis propria or beyond and may have metastasized to lymph nodes or
In the presence of complete esophageal obstruction without clinical evidence
of systemic metastasis, surgical excision of the tumor with mobilization of the
stomach to replace the esophagus has been the traditional means of relieving
the dysphagia. In the United States, the median age of patients who present
with esophageal cancer is 67 years. The results of a retrospective
review of 505 consecutive patients who were operated on by a single surgical
team over 17 years found no difference in the perioperative mortality, median
survival, or palliative benefit of esophagectomy on dysphagia when the group of
patients older than 70 years were compared to their younger peers.[Levels of
evidence: 3iiA and 3iiB] All of the patients in this series were selected for
surgery on the basis of potential operative risk. Age alone should not determine
therapy for patients with potentially resectable disease.
The optimal surgical procedure is controversial. One approach
advocates transhiatal esophagectomy with anastomosis of the stomach to the
cervical esophagus. A second approach advocates abdominal mobilization of the
stomach and transthoracic excision of the esophagus with anastomosis of the
stomach to the upper thoracic esophagus or the cervical esophagus. One study concluded that transhiatal esophagectomy was associated with lower morbidity than transthoracic esophagectomy with extended en bloc lymphadenectomy; however, median overall disease-free and quality-adjusted survival did not differ significantly. Similarly, no differences in long-term quality of life (QOL) using validated QOL instruments have been reported. In patients
with partial esophageal obstruction, dysphagia may, at times, be relieved by
placement of an expandable metallic stent  or by radiation therapy if the
patient has disseminated disease or is not a candidate for surgery.
Alternative methods of relieving dysphagia have been reported, including laser
therapy and electrocoagulation to destroy intraluminal tumor.
Surgical treatment of resectable esophageal cancers results in 5-year survival
rates of 5% to 30%, with higher survival rates in patients with early-stage
cancers. This is associated with a less than 10% operative mortality rate.
In an attempt to avoid this perioperative mortality and to relieve dysphagia,
definitive radiation therapy in combination with chemotherapy has been studied.
A Radiation Therapy Oncology Group randomized trial (RTOG-8501) of chemotherapy and radiation therapy versus radiation therapy
alone resulted in an improvement in 5-year survival for the combined modality
group (27% vs. 0%).[Level of evidence: 1iiA] An eight-year follow-up of this trial
demonstrated an overall survival (OS) rate of 22% for patients receiving
chemoradiation therapy. An Eastern Cooperative Oncology Group trial (EST-1282) of 135
patients showed that chemotherapy plus radiation provided a better 2-year
survival rate than radiation therapy alone, which was similar to that shown in the
Intergroup trial.[Level of evidence: 1iiA] In an attempt to improve upon the results
of RTOG-8501, Intergroup-0123 (RTOG-9405) randomly assigned 236 patients with
localized esophageal tumors to chemoradiation with high-dose radiation therapy
(64.8 Gy) and four monthly cycles of fluorouracil (5-FU) and cisplatin versus conventional-dose radiation therapy (50.4 Gy) and the same chemotherapy schedule.
Although originally designed to accrue 298 patients, this trial was closed in 1999 after a planned interim analysis showed that it was statistically unlikely that there would be any advantage to using high-dose radiation. At 2 years' median follow-up, no statistical differences were observed between the high-dose and
conventional-dose radiation therapy arms in median survival (13 months vs.
18 months), 2-year survival (31% vs. 40%), or local/regional failures (56%
vs. 52%).[Level of evidence: 1iiA]
Chemoradiation followed by surgery is a standard treatment option for patients with stages IB, II, III, and IVA esophageal cancer, based on the results of several randomized trials.
The ongoing CROSS (NCT01498289) study randomly assigned 366 patients with resectable esophageal or junctional cancers to receive either surgery alone or weekly administration of carboplatin (dose titrated to achieve an AUC [area under the curve] of 2 mg/mL/minute) and paclitaxel (50 mg/m2 of BSA [body surface area]) and concurrent radiation therapy (41.4 Gy in 23 fractions) administered over 5 weeks.[Level of evidence: 1iiA] The majority of the patients enrolled in the study have adenocarcinoma (75%).
With a median follow-up of 45 months, preoperative chemoradiation was found to improve median OS from 24 months in the surgery-alone group to 49.4 months (hazard ratio [HR], 0.657; 95% confidence interval [CI], 0.495–0.871, P = .003). Additionally, preoperative chemoradiation improved the rate of R0 resections (R0 is defined as complete resection with no tumor within 1 mm of resection margins, 92% vs. 69%, P < .001). A complete pathologic response was achieved in 29% of patients who underwent resection after chemoradiation therapy. Postoperative complications and in-hospital mortality were equivalent in both groups. The most common hematologic side effects in the chemoradiation group were leukopenia (6%) and neutropenia (2%). The most common nonhematologic side effects were anorexia (5%) and fatigue (3%).
Other phase III trials have compared preoperative concurrent chemoradiation therapy to
surgery alone for patients with esophageal cancer.[Level of evidence: 1iiA] A multicenter
prospective randomized trial in which preoperative combined chemotherapy
(i.e., cisplatin) and radiation therapy (37 Gy in 3.7 Gy fractions) followed by
surgery was compared to surgery alone in patients with squamous cell carcinoma
showed no improvement in OS and a significantly higher
postoperative mortality (12% vs. 4%) in the combined modality arm. In
patients with adenocarcinoma of the esophagus, a single-institution phase III
trial demonstrated a modest survival benefit (16 months vs. 11 months) for
patients treated with induction chemoradiation therapy consisting of 5-FU,
cisplatin, and 40 Gy (2.67 Gy fractions) plus surgery over resection
alone. A subsequent single-institution trial randomly assigned patients (75% with
adenocarcinoma) to 5-FU, cisplatin, vinblastine, and radiation
therapy (1.5 Gy twice daily to a total of 45 Gy) plus resection versus
esophagectomy alone. At a median follow-up of more than 8 years, there was no
significant difference between the surgery alone and combined modality therapy
with respect to median survival (17.6 months vs. 16.9 months), OS (16% vs. 30% at 3 years), or disease-free survival (16% vs. 28%
at 3 years). An Intergroup trial (CALGB-9781) planned to randomly assign 475 patients with resectable squamous cell or adenocarcinoma of the thoracic esophagus to treatment with preoperative chemoradiation therapy (5-FU, cisplatin, and 50.4 Gy) followed by esophagectomy and nodal dissection or surgery alone.[Level of evidence: 1iiA] The trial was closed as a result of poor patient accrual; however, the results of the 56 enrolled patients, with a median follow-up of 6 years, were reported. The median survival was 4.48 years (95% CI, 2.4 years to not estimable) for trimodality therapy versus 1.79 years (95% CI, 1.41–2.59 years) for surgery alone (P = .002), with 5-year OS of 39% (95% CI, 21%–57%) versus 16% (95% CI, 5%–33%) for trimodality therapy versus surgery alone.
A phase III German trial also compared induction chemotherapy (three courses of bolus 5-FU, leucovorin, etoposide, and cisplatin) followed by chemoradiation therapy (cisplatin, etoposide, and 40 Gy) followed by surgery (arm A), or the same induction chemotherapy followed by chemoradiation therapy (at least 65 Gy) without surgery (arm B) for patients with T3 or T4 squamous cell carcinoma of the esophagus.[Level of evidence: 1iiA] OS was the primary outcome. The analysis of 172 eligible, randomly assigned patients showed that OS at 2 years was not statistically significantly different between the two treatment groups (arm A: 39.9%; 95% CI, 29.4%–50.4%; arm B: 35.4%; 95% CI, 25.2%–45.6%; log-rank test for equivalence with 0.15, P < .007). Local progression-free survival (PFS) was higher in the surgery group (2-year PFS, 64.3%; 95% CI, 52.1%–76.5%) than in the chemoradiation therapy group (2-year PFS, 40.7%; 95% CI, 28.9%–52.5%; HR for arm B vs. arm A, 2.1; 95% CI, 1.3–3.5; P < .003). Treatment-related mortality was higher in the surgery group compared with the chemoradiation therapy group (12.8% vs. 3.5%, respectively; P < .03).
The effects of preoperative chemotherapy are being evaluated in randomized trials, as was done in the NCT00525785 trial.[Level of evidence: 1iiA]. An Intergroup trial randomly assigned 440 patients with local and operable esophageal cancer of any cell type to three cycles of preoperative 5-fluorouracil (5-FU) and cisplatin followed by surgery and two additional cycles of chemotherapy versus surgery alone. After a median follow-up of 55 months, there were no significant differences between the chemotherapy/surgery and surgery-alone groups in median survival (14.9 months and 16.1 months, respectively) or 2-year survival (35% and 37%, respectively). The addition of chemotherapy did not increase the morbidity associated with surgery. The Medical Research Council Oesophageal Cancer Working Party randomly assigned 802 patients with resectable esophageal cancer also of any cell type to two cycles of preoperative 5-FU and cisplatin followed by surgery versus surgery alone. At a median follow-up of 37 months, median survival was significantly improved in the preoperative chemotherapy arm (16.8 months vs. 13.3 months with surgery alone; difference 3.5 months; 95% CI, 1–6.5 months), as was 2-year OS (43% and 34% respectively; difference 9%; 95% CI, 3–14 months). The interpretation of the results from both of these trials is challenging because T or N staging was not reported and prerandomization and radiation could be offered at the discretion of the treating oncologist.
The Japanese Clinical Oncology Group randomly assigned 330 patients with clinical stage II or III, excluding T4, squamous cell carcinomas to receive either two cycles of preoperative cisplatin and 5-FU (fluorouracil) followed by surgery versus surgery followed by postoperative chemotherapy of the same regimen.[Level of evidence: 1iiC] A planned interim analysis was conducted after patient accrual, and although the primary endpoint of PFS was not met, there was a significant benefit in OS among patients treated with preoperative chemotherapy (P = .01). As a result of these findings, the Data and Safety Monitoring Committee recommended early publication.
With a median follow-up of 61 months, the 5-year OS was 55% among patients treated with preoperative chemotherapy compared with 43% among patients treated with postoperative chemotherapy (P = .04). However, there was no significant difference between groups with respect to PFS (5-year PFS, 39% vs. 44%; P = .22). Additionally, there were no significant differences between the two groups with respect to postoperative complications or treatment-related toxicities. Based on these results, preoperative chemotherapy without radiation therapy should still be considered under clinical evaluation.
Two randomized trials have shown no significant OS benefit
for postoperative radiation therapy over surgery alone.[Level of evidence: 1iiA] All newly
diagnosed patients should be considered candidates for therapies and
clinical trials comparing various treatment modalities.
Information about ongoing clinical trials is available from the NCI Web site.
Special attention to nutritional support is indicated in any patient undergoing
treatment of esophageal cancer. (Refer to the PDQ summary on Nutrition in Cancer Care for more information.)
Lerut T, Coosemans W, Van Raemdonck D, et al.: Surgical treatment of Barrett's carcinoma. Correlations between morphologic findings and prognosis. J Thorac Cardiovasc Surg 107 (4): 1059-65; discussion 1065-6, 1994.
Ginsberg RJ: Cancer treatment in the elderly. J Am Coll Surg 187 (4): 427-8, 1998.
Ellis FH Jr, Williamson WA, Heatley GJ: Cancer of the esophagus and cardia: does age influence treatment selection and surgical outcomes? J Am Coll Surg 187 (4): 345-51, 1998.
Hulscher JB, van Sandick JW, de Boer AG, et al.: Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med 347 (21): 1662-9, 2002.
de Boer AG, van Lanschot JJ, van Sandick JW, et al.: Quality of life after transhiatal compared with extended transthoracic resection for adenocarcinoma of the esophagus. J Clin Oncol 22 (20): 4202-8, 2004.
Saxon RR, Morrison KE, Lakin PC, et al.: Malignant esophageal obstruction and esophagorespiratory fistula: palliation with a polyethylene-covered Z-stent. Radiology 202 (2): 349-54, 1997.
Campbell WR Jr, Taylor SA, Pierce GE, et al.: Therapeutic alternatives in patients with esophageal cancer. Am J Surg 150 (6): 665-8, 1985.
Mellow MH, Pinkas H: Endoscopic therapy for esophageal carcinoma with Nd:YAG laser: prospective evaluation of efficacy, complications, and survival. Gastrointest Endosc 30 (6): 334-9, 1984.
Fleischer D, Sivak MV Jr: Endoscopic Nd:YAG laser therapy as palliation for esophagogastric cancer. Parameters affecting initial outcome. Gastroenterology 89 (4): 827-31, 1985.
Karlin DA, Fisher RS, Krevsky B: Prolonged survival and effective palliation in patients with squamous cell carcinoma of the esophagus following endoscopic laser therapy. Cancer 59 (11): 1969-72, 1987.
Kelsen DP, Bains M, Burt M: Neoadjuvant chemotherapy and surgery of cancer of the esophagus. Semin Surg Oncol 6 (5): 268-73, 1990.
Cooper JS, Guo MD, Herskovic A, et al.: Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA 281 (17): 1623-7, 1999.
Smith TJ, Ryan LM, Douglass HO Jr, et al.: Combined chemoradiotherapy vs. radiotherapy alone for early stage squamous cell carcinoma of the esophagus: a study of the Eastern Cooperative Oncology Group. Int J Radiat Oncol Biol Phys 42 (2): 269-76, 1998.
Minsky BD, Pajak TF, Ginsberg RJ, et al.: INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol 20 (5): 1167-74, 2002.
van Hagen P, Hulshof MC, van Lanschot JJ, et al.: Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366 (22): 2074-84, 2012.
Bosset JF, Gignoux M, Triboulet JP, et al.: Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med 337 (3): 161-7, 1997.
Walsh TN, Noonan N, Hollywood D, et al.: A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 335 (7): 462-7, 1996.
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 19 (2): 305-13, 2001.
Tepper J, Krasna MJ, Niedzwiecki D, et al.: Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol 26 (7): 1086-92, 2008.
Stahl M, Stuschke M, Lehmann N, et al.: Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 23 (10): 2310-7, 2005.
Kelsen DP, Ginsberg R, Pajak TF, et al.: Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med 339 (27): 1979-84, 1998.
Medical Research Council Oesophageal Cancer Working Group: Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet 359 (9319): 1727-33, 2002.
Ando N, Kato H, Igaki H, et al.: A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol 19 (1): 68-74, 2012.
Ténière P, Hay JM, Fingerhut A, et al.: Postoperative radiation therapy does not increase survival after curative resection for squamous cell carcinoma of the middle and lower esophagus as shown by a multicenter controlled trial. French University Association for Surgical Research. Surg Gynecol Obstet 173 (2): 123-30, 1991.
Fok M, Sham JS, Choy D, et al.: Postoperative radiotherapy for carcinoma of the esophagus: a prospective, randomized controlled study. Surgery 113 (2): 138-47, 1993.
Stage 0 squamous esophageal cancer is rarely seen in the United States, but
surgery has been used for this stage of cancer.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Rusch VW, Levine DS, Haggitt R, et al.: The management of high grade dysplasia and early cancer in Barrett's esophagus. A multidisciplinary problem. Cancer 74 (4): 1225-9, 1994.
Heitmiller RF, Redmond M, Hamilton SR: Barrett's esophagus with high-grade dysplasia. An indication for prophylactic esophagectomy. Ann Surg 224 (1): 66-71, 1996.
Standard treatment options:
Treatment options under clinical evaluation:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Standard treatment options:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
At diagnosis, approximately 50% of patients with esophageal cancer will have
metastatic disease and will be candidates for palliative therapy.
Many agents are active in esophageal cancer. Objective response rates of 30%
to 60% and median survivals of less than 1 year are commonly reported with
platinum-based combination regimens with fluorouracil, taxanes, topoisomerase inhibitors, hydroxyurea, or vinorelbine.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Enzinger PC, Ilson DH, Kelsen DP: Chemotherapy in esophageal cancer. Semin Oncol 26 (5 Suppl 15): 12-20, 1999.
Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.
Sur RK, Levin CV, Donde B, et al.: Prospective randomized trial of HDR brachytherapy as a sole modality in palliation of advanced esophageal carcinoma--an International Atomic Energy Agency study. Int J Radiat Oncol Biol Phys 53 (1): 127-33, 2002.
Gaspar LE, Nag S, Herskovic A, et al.: American Brachytherapy Society (ABS) consensus guidelines for brachytherapy of esophageal cancer. Clinical Research Committee, American Brachytherapy Society, Philadelphia, PA. Int J Radiat Oncol Biol Phys 38 (1): 127-32, 1997.
Waters JS, Norman A, Cunningham D, et al.: Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. Br J Cancer 80 (1-2): 269-72, 1999.
Ross P, Nicolson M, Cunningham D, et al.: Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol 20 (8): 1996-2004, 2002.
Taïeb J, Artru P, Baujat B, et al.: Optimisation of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of hydroxyurea, leucovorin, 5-FU and cisplatin (HLFP regimen) for metastatic oesophageal cancer. Eur J Cancer 38 (5): 661-6, 2002.
Conroy T, Etienne PL, Adenis A, et al.: Vinorelbine and cisplatin in metastatic squamous cell carcinoma of the oesophagus: response, toxicity, quality of life and survival. Ann Oncol 13 (5): 721-9, 2002.
All recurrent esophageal cancer patients present difficult problems in
palliation. All patients, whenever possible, should be considered candidates
for clinical trials as outlined in treatment overview.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
This information was last updated on July 31, 2014.