Esophageal cancer
Esophageal cancer occurs in your esophagus, the long, hollow tube that connects your throat to your stomach.
Even though esophageal cancer can start and occur anywhere in the esophagus, it typically begins in the inner layer of the esophagus wall and moves outward.
Overview
The esophagus sits in front of your spine and behind the trachea (your windpipe). Your esophagus is made up of four different parts, including the upper esophageal sphincter, the lumen, the gastroesophageal junction (GE) and the lower esophageal sphincter.
Located at the opening of the upper esophagus, the upper esophageal sphincter is a ring of muscle that allows food or liquid to pass through it.
Food and liquids that you swallow move to the inside of the esophagus, called the lumen, towards the stomach.
The gastroesophageal (GE) junction is the name of the connection point where the lower part of the esophagus meets the stomach.
Another ring of muscle near the GE junction, the lower esophageal sphincter, allows food from the esophagus into the stomach. When you’re not eating or drinking, it stays closed to keep acid and digestive juices from the stomach out of the esophagus.
The esophagus wall
The esophagus wall consists of four layers: the mucosa, submucosa, muscularis propria and adventitia.
Mucosa. This layer lines the inside of the esophagus and has 3 parts:
- The innermost lining is called the epithelium and is usually made up of squamous cells. Most esophageal cancers start here.
- The thin layer of connective tissue right under the epithelium is called the lamina propria.
- The thin layer of muscle under the lamina propria is called the muscularis mucosa.
Submucosa. Just below the mucosa is a layer of connective tissue called the submucosa that contains blood vessels and nerves.
Muscularis propria. Under the submucosa is a thick layer of muscle called the muscularis propria that helps push food down the esophagus from the throat to the stomach.
Adventitia. Made up of connective tissue, the adventitia is the outermost layer of the esophagus.
Esophageal cancer symptoms
Symptoms
See your UCHealth providers if you have any of these symptoms:
- Trouble swallowing.
- Chest pain.
- Weight loss.
- Hoarseness.
- Chronic cough.
- Vomiting.
- Bone pain (if cancer has spread to the bone).
- Bleeding into the esophagus. This blood then passes through the digestive tract, which may turn the stool black. Over time, this blood loss can lead to anemia (low red blood cell levels), which can make a person feel tired.
Source: American Cancer Society
Risk factors
Although there are many different risk factors for esophageal cancer, what defines a risk factor is pretty simple: whatever increases the chances of getting the disease.
However, it’s important to note that not all risk factors are the same for all diseases, not everyone who has risk factors get esophageal cancer and not everyone who gets the disease will have any risk factors. Some risk factors, including lifestyle choices like smoking and alcohol use, can be controlled, while others like age and family history cannot.
Below are several known factors that can increase your risk of getting adenocarcinoma or squamous cell carcinoma of the esophagus.
Age
Statistically speaking, the older a person is, the higher the chance of getting esophageal cancer. More than 85% of cases are found in people older than age 55.
Gender
Men are more likely than women to get esophageal cancer.
Tobacco and alcohol use
Tobacco products are a major risk factor for esophageal cancer. The frequency of tobacco usage is directly proportional to the amount of cancer risk.
Compared to a non-smoker, smoking at least a pack of cigarettes a day more than doubles a smoker’s chance of getting adenocarcinoma, even if the usage stops. The chance of getting squamous cell esophageal cancer is even higher, but quitting does decrease the risk.
Alcohol consumption also increases the risk of esophageal cancer. And, as with smoking, the higher the usage, the higher the risk. Drinking alcohol tends to increase the risk of getting squamous cell carcinoma more than adenocarcinoma.
Combining both smoking and drinking alcohol increases the chances of getting squamous cell carcinoma much more than using either by itself.
Gastroesophageal reflux disease (GERD)
When stomach acid escapes into the lower part of the esophagus it results in gastroesophageal reflux disease (GERD). For most people, reflux causes a feeling of heartburn or pain in the chest. GERD results in a slightly higher risk of getting adenocarcinoma and seems to be higher in people with more frequent symptoms. However, most of the people who have GERD don’t end up getting esophageal cancer. GERD can also cause Barrett’s esophagus which is linked to an even higher risk.
Barrett’s esophagus
If someone suffers from reflux for a long time, the inner lining of their esophagus becomes damaged and their normal squamous cells become gland cells. This is known as Barrett’s (or Barrett) esophagus.
Obesity
Being overweight or obese results in a higher likelihood of getting adenocarcinoma of the esophagus.
Diet
Certain foods, like processed meat, may increase the chance of developing esophageal cancer, but eating lots of fruits and vegetables seems to lower that same risk. Frequently drinking very hot liquids may also increase the risk for squamous cell carcinoma.
Physical activity
Staying physically active may lower the risk of esophageal cancer.
Achalasia
Achalasia results when the muscle between the lower esophagus and the stomach fails to properly relax, allowing food to stay in that area longer than usual. Over time, the lower esophagus stretches out and the lining of the esophagus becomes irritated.
Achalasia elevates the risk of esophageal cancer many times above normal. It typically takes about 15 to 20 years for cancer to appear after the onset of achalasia.
Tylosis
Tylosis causes thickening of the skin on the palms of the hands and soles of the feet along with small growths called papillomas in the esophagus. People with this inherited disease are at a very high risk of getting squamous cell carcinoma.
Plummer-Vinson syndrome
This rare syndrome causes webs to form in the upper part of the esophagus.
History of certain other cancers
People with a history of other cancers associated with smoking, such as lung cancer, oral cancer and throat cancer face a higher risk of getting squamous cell carcinoma of the esophagus as well.
Diagnosis and staging
Diagnosis – Testing people at high risk.
Barrett’s esophagus
If you’re someone at a high risk of esophageal cancer (including those with Barrett’s esophagus), one of the best ways to get an accurate diagnosis is to get regularly tested with an upper endoscopy. The test is fairly simple, with the doctor using an endoscope to look at the inside of your esophagus. The doctor will typically remove some abnormal tissue (called a biopsy) so it can be scanned in the lab to look for cancer or pre-cancer.
Inherited syndromes
It’s also important for people with certain inherited syndromes to get tested with regular endoscopies to look for cancer or pre-cancer. For example, people over the age of 20 with Tylosis or Bloom syndrome should get an upper endoscopy. And people over the age of 40 who have family members with familial (inherited) Barrett’s esophagus should also consider an upper endoscopy screening.
Esophageal cancer staging
The process of determining if cancer is spread, and how far, is called staging. Staging gives doctors and patients a universal language to describe how much cancer is in the body, how serious the cancer is and how best to treat it. Staging is also useful in helping doctors talk about survival statistics.
The range of stages for esophageal cancers is stage 0 through stage 4. The lower the number, the less severe the cancer is and the less it has spread. Conversely, the higher the number, the more the cancer has spread.
How is the stage determined?
The staging system most often used for esophageal cancer is the American Joint Committee on Cancer (AJCC) TNM system, which is based on 3 key pieces of information:
- The extent (size) of the tumor (T): How far has the cancer grown into the wall of the esophagus? Has the cancer reached nearby structures or organs?
- The spread to nearby lymph nodes (N): Has the cancer spread to nearby lymph nodes?
- The spread (metastasis) to distant sites (M): Has the cancer spread to distant lymph nodes or distant organs such as the lungs or liver?
Numbers or letters after T, N, and M provide more details about each of these factors. Higher numbers mean the cancer is more advanced. Once a person’s T, N, and M categories have been determined, this information is combined in a process called stage grouping to assign an overall stage.
Staging systems for esophageal cancer
Since esophageal cancer can be treated in different ways, different staging systems have been created for each situation:
- Pathological stage (also called the surgical stage). If surgery is done first, the pathological stage is determined by examining tissue removed during an operation. This is the most common system used.
- Clinical stage. If surgery might not be possible or will be done after other treatment is given, then the clinical stage is determined based on the results of a physical exam, biopsy, and imaging tests. The clinical stage will be used to help plan treatment, but it might not predict outlook as accurately as the pathologic stage. This is because sometimes the cancer has spread further than the clinical stage estimates.
- Postneoadjuvant stage. If chemotherapy or radiation is given before surgery (this is called neoadjuvant therapy), then a separate postneoadjuvant stage will be determined after surgery.
Grade
Another factor that can affect your treatment and your outlook is the grade of your cancer. The grade describes how closely the cancer looks like normal tissue when seen through a microscope.
The scale used for grading esophagus cancers is from 1 to 3.
- GX: The grade cannot be evaluated. (The grade is unknown).
- Grade 1 (G1: well differentiated; low grade) means the cancer cells look more like normal esophagus cells.
- Grade 3 (G3: poorly differentiated, undifferentiated; high grade) means the cancer cells look very abnormal.
- Grades 2 (G2: moderately differentiated; intermediate) falls somewhere in between Grade 1 and Grade 3.
Low-grade cancers tend to grow and spread more slowly than high-grade cancers. Most of the time, the outlook is better for low-grade cancers than it is for high-grade cancers of the same stage.
Location
Some stages of early squamous cell carcinoma also take into account where the tumor is in the esophagus. The location is assigned as either upper, middle, or lower based on where the middle of the tumor is.
Esophageal cancer stage descriptions
The tables below are simplified versions of the TNM system, based on the most recent AJCC systems effective January 2018. They include staging systems for squamous cell carcinoma and adenocarcinoma.
It’s important to know that esophageal cancer staging can be complex. If you have any questions about the stage of your cancer or what it means, please ask your doctor to explain it to you in a way you understand.
Squamous cell carcinoma stages
| AJCC Stage | Stage description: squamous cell carcinoma |
|---|---|
| 0 | The cancer is only in the epithelium (the top layer of cells lining the inside of the esophagus). It has not started growing into the deeper layers. This stage is also known as high-grade dysplasia. It has not spread to any lymph nodes or distant organs. The cancer grade does not apply. The cancer can be located anywhere in the esophagus. |
| IA | The cancer is growing into the lamina propria or muscularis mucosa (the tissue under the epithelium). It has not spread to any lymph nodes or distant organs. The cancer is grade 1 or an unknown grade and located anywhere in the esophagus. |
| IB | The cancer is growing into the lamina propria, muscularis mucosa (the tissue under the epithelium), submucosa or the thick muscle layer (muscularis propria). It has not spread to nearby lymph nodes or to distant organs. The cancer can be any grade or an unknown grade and located anywhere in the esophagus. |
| IIA | The cancer is growing into the thick muscle layer (muscularis propria). It has not spread to nearby lymph nodes or to distant organs. The cancer can be grade 2 or 3 or an unknown grade and located anywhere in the esophagus. |
| OR | |
| The cancer is growing into the outer layer of the esophagus (the adventitia). It has not spread to nearby lymph nodes or to distant organs.The cancer can be any of the following: - Any grade and located in the lower esophagus OR - Grade 1 and located in the upper or middle esophagus. | |
| IIB | The cancer is growing into the outer layer of the esophagus (the adventitia). It has not spread to nearby lymph nodes or to distant organs. The cancer can be any of the following: - Grade 2 or 3 and located in the upper or middle of the esophagus OR - An unknown grade and located anywhere in the esophagus OR - Any grade and have an unknown location in the esophagus. |
| OR | |
| The cancer is growing into the lamina propria, muscularis mucosa (the tissue under the epithelium) or into the submucosa. It has spread to 1 or 2 nearby lymph nodes. The cancer can be any grade and located anywhere in the esophagus. | |
| IIIA | The cancer is growing into the lamina propria, muscularis mucosa (the tissue under the epithelium), submucosa or the thick muscle layer (muscularis propria). It has spread to no more than 6 nearby lymph nodes. It has not spread to distant organs. The cancer can be any grade and located anywhere in the esophagus. |
| IIIB | The cancer is growing into: - The thick muscle layer (muscularis propria) and spread to no more than 6 nearby lymph nodes OR - The outer layer of the esophagus (the adventitia) and spread to no more than 6 nearby lymph nodes OR - The pleura (the thin layer of tissue covering the lungs), the pericardium (the thin sac surrounding the heart), or the diaphragm (the muscle below the lungs that separates the chest from the abdomen) and spread to no more than 2 nearby lymph nodes. It has not spread to distant organs. The cancer can be any grade and located anywhere in the esophagus. |
| IVA | The cancer is growing into: - The pleura (the thin layer of tissue covering the lungs), the pericardium (the thin sac surrounding the heart), or the diaphragm (the muscle below the lungs that separates the chest from the abdomen) and spread to no more than 6 nearby lymph nodes OR - The trachea (windpipe), the aorta (the large blood vessel coming from the heart), the spine, or other crucial structures and no more than 6 nearby lymph nodes OR - Any layers of the esophagus and spread to 7 or more nearby lymph nodes. It has not spread to distant organs. The cancer can be any grade and located anywhere in the esophagus. |
| IVB | The cancer has spread to distant lymph nodes and/or other organs. such as the liver and lungs. The cancer can be any grade and located anywhere in the esophagus. |
Andenocarcinoma stages
The location of the cancer in the esophagus does not affect the stage of adenocarcinomas.
| AJCC Stage | Stage description: adenocarcinoma |
|---|---|
| 0 | The cancer is only in the epithelium (the top layer of cells lining the inside of the esophagus). It has not started growing into the deeper layers. This stage is also known as high-grade dysplasia. It has not spread to any lymph nodes or distant organs. The cancer grade does not apply. |
| IA | The cancer is growing into the lamina propria or muscularis mucosa (the tissue under the epithelium). It has not spread to any lymph nodes or distant organs. The cancer is grade 1 or an unknown grade. |
| IB | The cancer is growing into the lamina propria, muscularis mucosa (the tissue under the epithelium), or the submucosa. It has not spread to nearby lymph nodes or to distant organs. The cancer can be grade 1 or 2 or an unknown grade. |
| IC | The cancer is growing into the lamina propria, muscularis mucosa (the tissue under the epithelium), submucosa or the thick muscle layer (muscularis propria). It has not spread to nearby lymph nodes or to distant organs. The cancer can be grade 1, 2 or 3. |
| IIA | The cancer is growing into the thick muscle layer (muscularis propria). It has not spread to nearby lymph nodes or to distant organs. The cancer can be grade 3 or an unknown grade. |
| IIB | The cancer is growing into the lamina propria, muscularis mucosa (the tissue under the epithelium), or the submucosa. It has spread to 1 or 2 nearby lymph nodes. It has not spread to distant organs. The cancer can be any grade. |
| OR | |
| The cancer is growing into the outer layer of the esophagus (the adventitia). It has not spread nearby lymph nodes. The cancer can be any grade. | |
| IIIA | The cancer is growing into the lamina propria, muscularis mucosa (the tissue under the epithelium), the submucosa, or the thick muscle layer (muscularis propria).It has spread to no more than 6 nearby lymph nodes. It has not spread to distant organs. The cancer can be any grade. |
| IIIB | The cancer is growing into: - The thick muscle layer (muscularis propria) and spread to no more than 6 nearby lymph nodes OR - The outer layer of the esophagus (the adventitia) and spread to no more than 6 nearby lymph nodes OR - The pleura (the thin layer of tissue covering the lungs), the pericardium (the thin sac surrounding the heart), or the diaphragm (the muscle below the lungs that separates the chest from the abdomen) and spread to no more than 2 nearby lymph nodes. It has not spread to distant organs. The cancer can be any grade. |
| IVA | The cancer is growing into: - The pleura (the thin layer of tissue covering the lungs), the pericardium (the thin sac surrounding the heart), or the diaphragm (the muscle below the lungs that separates the chest from the abdomen) and spread to no more than 6 nearby lymph nodes OR - The trachea (windpipe), the aorta (the large blood vessel coming from the heart), the spine, or other crucial structures and no more than 6 nearby lymph nodes OR - Any layers of the esophagus and spread to 7 or more nearby lymph nodes. It has not spread to distant organs. The cancer can be any grade. |
| IVB | The cancer has spread to distant lymph nodes and/or other organs. such as the liver and lungs. The cancer can be any grade. |
Treatment and recovery
Esophagectomy
An esophagectomy is a surgery that removes some or most of the esophagus. The amount of the esophagus removed depends upon the stage of the tumor and its location. Removing the esophagus (and nearby lymph nodes) may cure the cancer If it hasn’t yet spread far beyond the esophagus.
There are several different ways to perform esophagectomy, each of which requires a complex operation that may require an extended hospital stay:
Open esophagectomy. In an open esophagectomy, the surgeon makes large incisions in a combination of the neck, chest or abdomen (and sometimes in all three).
- A transhiatal esophagectomy has its main incisions in the neck and abdomen.
- A transthoracic esophagectomy has its main incisions in the chest and abdomen.
Minimally invasive esophagectomy. If the cancer is small enough or caught early enough, the esophagus can sometimes be removed through a much less invasive procedure involving several smaller incisions. The surgeon will insert a laparoscope (a thin flexible tube with a light) into one small incision and surgical instruments through other small incisions. Because it doesn’t involve the large incisions of other procedures, minimally invasive esophagectomy may help reduce time in the hospital and speed up recovery time.
Lymph node removal
No matter the type of esophagectomy, nearby lymph nodes (typically at least 15) will also be removed to see if they have cancer cells. If they do show cancer, your doctor will likely recommend additional treatments like chemotherapy and/or radiation post surgery.
Surgery for palliative care
Palliative care involves minor surgery designed to prevent or relieve problems caused by the cancer instead of trying to cure the cancer itself. An example of this would be placing a feeding tube directly into the stomach or small intestine of a patient who wasn’t getting enough nutrition on their own.
Radiation therapy
Radiation therapy uses concentrated x-rays to destroy cancer cells and is often used as the main treatment for people who either can’t have or don’t want surgery. To most effectively treat esophageal cancer, radiation therapy is often combined with chemotherapy (chemoradiation) and/or surgery.
Radiation therapy used before surgery is called neoadjuvant treatment and it tries to shrink the cancer to make removal easier.
Radiation therapy used after surgery is called adjuvant treatment and it attempts to kill any remaining cancer cells that may still exist.
Types of radiation therapy. Doctors can offer two main types of radiation therapy to treat esophageal cancer.
- External-beam radiation therapy (EBRT), the most common type of treatment for esophageal cancer, uses a machine outside the body to direct intense radiation at the cancer. The frequency and duration of the treatments depends on why the radiation is being given as well as other factors. Treatments can span a few days to weeks.
- Internal radiation therapy (brachytherapy) uses an endoscope (a long, flexible tube) to go down the throat and place radioactive material right next to the tumor for a short time. Because the radiation only has to travel a short distance, it effectively reaches the tumor without impacting nearby normal tissues. The result is fewer side effects than with EBRT.
Targeted therapy
As research reveals more about the mutations in cells that cause cancer, doctors develop breakthrough drugs designed to target those exact changes. Because they’re made to work differently than standard chemotherapy drugs, targeted drugs will sometimes have different side effects and be more effective than standard chemo drugs.
Immunotherapy
Immunotherapy is the use of medicines that help a person’s own immune system find and destroy cancer cells more effectively. It can be used to treat some people with esophageal cancer.
Type of esophageal cancer
There are two main types of esophageal cancer, depending on the type of cell it starts in.
Squamous cell carcinoma
Squamous cell carcinoma gets its name because the mucosa, the inner layer of the esophagus, is normally lined with squamous cells. Although it can occur anywhere along the esophagus, squamous cell carcinoma is most often found in the neck region (cervical esophagus) and in the upper two-thirds of the chest cavity (upper and middle thoracic esophagus). Once the most common type of esophageal cancer in the United States, squamous cell carcinoma now comprises less than 30% of esophageal cancers in this country.
Adenocarcinoma
Adenocarcinomas are cancers that start in gland cells (the cells that make mucus) and are often found in the lower third of the esophagus (lower thoracic esophagus).
Gastroesophageal (GE) junction tumors
Adenocarcinomas that start at the GE junction, the area where the esophagus joins the stomach, typically behave like cancers in the esophagus and tend to be treated like them.
Causes of esophageal cancer
What causes most esophageal cancers is not yet known, but there are certain risk factors that can increase the likelihood of getting esophageal cancer.
Inherited gene mutations
When a DNA mutation is passed on through heredity and is found in all of a person’s cells, it’s called an inherited mutation. Inherited gene mutations cause a very small number of esophageal cancers.
Acquired gene mutations
Most cases of esophageal cancer are caused by DNA mutations that aren’t inherited. These are called acquired gene mutations, meaning they’re acquired during a person’s life. While it’s believed that certain risk factors like tobacco and alcohol use do contribute to these acquired mutations, the exact causes are still unknown.
Five-year esophageal cancer survival rates
Data source: Surveillance, Epidemiology, and End Results (SEER) 17 registries, National Cancer Institute, 2022. AJCC All Stages, 5 Year Relative Survival. Date of diagnosis from 2012 – 2018.
References
National Cancer Institute (NCI). Esophageal Cancer Treatment (https://www.cancer.gov/types/esophageal/patient/esophageal-treatment-pdq)
MedlinePlus: National Library of Medicine. Esophageal Cancer (https://medlineplus.gov/esophagealcancer.html)
National Center for Biotechnology Information (NCBI): National Library of Medicine. Etiology and Prevention of Esophageal Cancer (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040887/)