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by Dr. C.H. Weaver M.D. 6/2022

Esophageal cancer is relatively uncommon and can be very deadly. Each year in the United States, there are roughly 17,000 individuals diagnosed with esophageal cancer and 15,000 deaths from the disease.1

  • Signs & Symptoms
  • Risk Factors for Esophageal Cancer
  • Diagnosis & Tests for Esophageal Cancer
  • Biomarker-Genomic Testing for Precision Cancer Medicines
  • Staging of Esophageal Cancer
  • Treatment of Esophageal Cancer
Esophageal Cancer CancerConnect

The 5-year survival rate for all patients diagnosed with esophageal cancer is approximately 18%, with most survivors having cancer that has not spread outside the esophagus (stage 0-II). This low survival is due to a combination of factors including advanced age and poor overall health at diagnosis, the presence of local and distant spread of cancer at diagnosis, and the fact that most patients have some minimal residual cancer remaining after primary treatment with surgical resection.2

The esophagus is the muscular tube that conveys food from the back of the throat to the stomach. It is part of a person’s gastrointestinal (GI) tract. When a person swallows, the walls of the esophagus squeeze together to push food down into the stomach. The connection of the esophagus to the stomach at the diaphragm is called the gastro-esophageal junction. The gastro-esophageal junction serves as a one-way valve to keep stomach contents from being refluxed or regurgitated back into the esophagus.

If stomach contents reflux back into the esophagus the surface lining can be damaged due to the acidity of these contents. One symptom of regurgitation of stomach contents into the lower esophagus is heartburn. Heartburn is often associated with a “hiatal hernia,” which is a condition where the upper part of the stomach pushes up above the diaphragm and into the chest. Normally, the esophagus is lined with squamous epithelial cells; however, when reflux occurs, these cells are replaced by columnar epithelium, which is prone to develop a type of cancer called adenocarcinoma. This phenomenon is known as Barrett’s esophagus.

There are 2 major types of esophageal cancer:

  • Squamous cell carcinoma. Typically starts in squamous cells that line the esophagus in the upper and middle part of the esophagus.
  • Adenocarcinoma. Begins in the glandular tissue in the lower part of the esophagus where the esophagus and the stomach come together.

Over the past two decades, there has been a dramatic increase in the incidence of adenocarcinomas, which now account for one-third to one-half of all esophageal cancers. Most of the adenocarcinomas of the lower esophagus are thought to arise in the setting of Barrett’s esophagus.

Outcomes of treatment for squamous cell cancer and adenocarcinoma of the esophagus are very similar, except for the responsiveness of the cancer to some chemotherapy drugs. The results of treatment of squamous cell cancer and adenocarcinoma are included together unless otherwise specified.

Symptoms & Signs of Esophageal Cancer

Individuals with esophageal cancer may experience the following symptoms or signs. Sometimes, people with esophageal cancer do not have any of these changes, or the cause of a symptom may be another medical condition that is not cancer.

  • Difficulty and pain with swallowing, particularly when eating meat, bread, or raw vegetables. As the tumor grows, it can block the pathway to the stomach. Even liquid may be painful to swallow.
  • Pressure or burning in the chest
  • Indigestion or heartburn
  • Vomiting
  • Frequent choking on food
  • Unexplained weight loss
  • Coughing or hoarseness
  • Pain behind the breastbone or in the throat

Cause of Esophageal Cancer

Esophageal cancer begins when healthy cells acquire a genetic change (mutation) that causes them to turn into abnormal cells.

Risk factors for Esophageal Cancer

A risk factor is anything that increases a person’s chance of developing cancer. Risk factors can influence the development of cancer but most do not directly cause cancer. Many individuals with risk factors will never develop cancer and others with no known risk factors will. Most esophageal cancers develop sporadically, which means for no known reason. Some esophageal cancers however are more likely to develop in individuals with certain risk factors that increase an individuals chance of developing esophageal cancer.

The following factors may raise a person’s risk for developing esophageal cancer:1,2

  • Age. People between the ages of 45 and 70 have the highest risk of esophageal cancer.
  • Gender. Men are 3 to 4 times more likely than women to develop esophageal cancer.
  • Race. Black people are twice as likely to develop the squamous cell type of esophageal cancer.
  • Tobacco. Using any form of tobacco: cigarettes, cigars, pipes, chewing tobacco, and snuff increases the risk of esophageal cancer,
  • Alcohol. Heavy drinking over a long period of time increases the risk of developing esophageal cancer, especially when combined with tobacco use.
  • Barrett’s esophagus. People with Barrett’s esophagus are more likely to develop adenocarcinoma of the esophagus.
  • Diet/nutrition. A diet that is low in fruits and vegetables and certain vitamins and minerals may increase a person’s risk.
  • Obesity. Being severely overweight and having too much body fat can increase a person’s risk.
  • Lye. Children who have accidentally swallowed lye have an increased risk. Lye can be found in some cleaning products, such as drain cleaners.
  • Achalasia. Achalasia is a condition when the lower muscular ring of the esophagus does not relax during swallowing of food.

Diagnosis & Tests for Esophageal Cancer

Doctors use many tests to find, or diagnose, cancer. They also do tests to learn if cancer has spread to another part of the body from where it started. A biopsy is the only certain way to confirm a diagnosis of esophageal cancer. When performing a biopsy, the doctor takes a sample of tissue for testing in a laboratory. The doctor may recommend some or all of these tests to help make a diagnosis.

Histological Types of Esophageal Cancer

Barrett’s Esophagus: Barrett’s esophagus involves the abnormal presence of columnar epithelium in the surface lining of the lower esophagus, which should only contain squamous cells. This abnormal epithelium is prone to develop pre-cancerous, or pre-malignant, changes called dysplasia, which are further characterized as either low-grade or high-grade. Dysplasia is a term for abnormalities in cells that do not appear normal under the microscope, but are not yet characteristic of invasive cancer. Currently, physicians and researchers believe that under certain conditions, dysplasia in the esophagus may be reversed and the subsequent development of cancer prevented.

Squamous Cell Cancer: Squamous cell cancer arises from normal squamous epithelium of the esophagus.

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Adenocarcinoma: Adenocarcinoma is a type of cancer that arises from columnar epithelium that is characteristic of the stomach and intestines. Adenocarcinoma of the lower esophagus is thought to usually arise from Barrett’s esophagus.

Genomic or Biomarker Testing-Precision Cancer Medicine

The purpose of precision cancer medicine is to define the genomic alterations in the cancers DNA that are driving that specific cancer. Precision cancer medicine utilizes molecular diagnostic & genomic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.

By testing a cancer for specific unique biomarkers doctors can offer the most personalized treatment approach utilizing precision medicines. Human epidermal growth receptor 2 (HER2) is a specialized protein found on the surface of cells that can be targeted with precision cancer medicines as is PD-1.1

Staging of Esophageal Cancer

When diagnosed with esophageal cancer further tests are necessary to determine the extent of spread (stage) of the cancer. Cancer’s stage is a key factor in determining the best treatment.

It is important to determine the extent of spread of the cancer before treatment in order to select the best treatment option. Of particular concern is the presence of cancer in lymph nodes, spread of cancer to distant sites or local extension of cancer into surrounding structures, which might make attempts to remove all cancer with surgical resection impossible. Unfortunately, in many cases the true extent of spread of cancer can only be determined by surgical resection. Frequently, more advanced cancer is found at surgery than was detected by clinical tests. In addition to a physical examination, the following tests may be used to stage esophageal cancer:

  • Barium swallow, (esophagram). The patient swallows a liquid containing barium and then a series of x-rays are taken. Barium coats the surface of the esophagus, making cancer or other unusual changes easier to see on the x-ray. If there is an abnormal looking area,an upper endoscopy and biopsy to find out if it is cancerous is typically performed.
  • Computed Tomography (CT) Scan: A CT scan is a technique for imaging body tissues and organs, during which X-ray transmissions are converted to detailed images, using a computer to synthesize X-ray data. A CT scan is conducted with a large machine positioned outside the body that can rotate to capture detailed images of the organs and tissues inside the body.
  • Magnetic Resonance Imaging (MRI): MRI uses a magnetic field rather than X-rays, and can often distinguish more accurately between healthy and diseased tissue than a CT. An MRI gives a better picture of cancer located near bone than does CT, does not use radiation, and provides pictures from various angles that enable doctors to construct a three-dimensional image of the cancer.
  • Positron emission tomography (PET): Positron emission tomography scanning is an advanced technique for imaging body tissues and organs. One characteristic of living tissue is the metabolism of sugar. Prior to a PET scan, a substance containing a type of sugar attached to a radioactive isotope (a molecule that emits radiation) is injected into the patient’s vein. The cancer cells “take up” the sugar and attached isotope, which emits positively charged, low energy radiation (positrons) that create the production of gamma rays that can be detected by the PET machine to produce a picture. If no gamma rays are detected in the scanned area, it is unlikely that the mass in question contains living cancer cells.
  • Upper endoscopy or esophagus-gastric-duodenoscopy (EGD). An upper endoscopy is an examination performed through an endoscope, which is a thin flexible tube with a light and camera. The endoscope is inserted through the mouth into the esophagus and allows the physician to visualize, photograph, and biopsy the suspicious areas for cancer.
  • Thoracoscopy: A thoracoscopy is another procedure performed through an endoscope to examine the chest in order to determine the extent of spread of cancer in the chest.
  • Laparoscopy: Laparoscopy is a procedure that involves the insertion of an endoscope through a small incision in the abdomen. Laparoscopy is an important tool for staging and has proven to be more reliable than CT scanning in detecting spread of cancer to the liver and the lining of the abdomen (peritoneum).
  • Bronchoscopy. The doctor passes a thin, flexible tube with a light on the end into the mouth or nose, down through the windpipe, and into the breathing passages of the lungs. A bronchoscopy may be performed if a patient’s tumor is located in the upper two-thirds of the esophagus to find out if the tumor is growing into the person’s airway.
  • Endosonography: Endosonography refers to an ultrasound test performed through an endoscope. Ultrasound tests utilize sound waves to detect different densities of tissue, including cancer. Endosonography can detect spread of cancer into various layers of the stomach, adjacent organs and lymph nodes better than CT scanning.
Gastrointestinal Cancer Newsletter 490 GI

Stages of Esophageal Cancer

In order to learn more about the most recent information available concerning the treatment of esophageal cancer, click on the appropriate stage.

Barrett’s Esophagus: There are essentially three categories of abnormal changes in the surface lining of the lower esophagus: 

  1. Barrett’s esophagus (presence of columnar epithelium) without other changes
  2. Barrett’s esophagus with low-grade dysplasia and
  3. Barrett’s esophagus with high-grade dysplasia.

Stage 0: Cancer in situ is cancer that is limited to the surface epithelium. There can be extensive spread along the surface of the lining of the esophagus, but there is no spread of cancer below the surface into lymph nodes or to distant sites.

Stage I: Cancer invades beneath the surface lining, but does not invade the muscular part of the wall of the esophagus and there is no spread to lymph nodes or distant spread of cancer.

Stage II: Cancer invades into or through the muscle of the wall of the esophagus, but not into local structures (IIA). When there is regional lymph node involvement with any extent of primary cancer but no invasion of local structures, this is called stage IIB.

Stage III: Cancer invades through the muscular wall of the esophagus with lymph node spread and/or invasion of adjacent structures.

Stage IV: The cancer has spread to distant sites

Recurrent Cancer: The cancer has recurred after primary treatment.

Next: Treatment - Management of Esophageal Cancer


  1. American Cancer Society. Cancer Facts & Figures 2021.