All About Esophageal Cancer

Author: OncoLink Team
Last Reviewed:

What is the esophagus?

The esophagus is a long muscular tube around 25 centimeters (about 9 inches) long that connects the mouth to the stomach. The wall of the esophagus is made up of a series of muscles that help move food down the throat into the stomach (called peristalsis). The esophagus is lined with two layers of tissue: the mucosa and submucosa. The throat (or pharynx) is continuous with the esophagus. The esophagus is thought to start a few centimeters below the thyroid cartilage (Adam's apple). The esophagus travels down through the chest, between the lungs. It then passes through a hole in the diaphragm and connects with the stomach. There is a ring of muscle, known as the lower esophageal sphincter, between the stomach and esophagus. It prevents food and stomach acid from going back up into the esophagus.

What is esophageal cancer?

Cancer is when cells grow in an uncontrolled way which can lead to a tumor developing. Cancers are described by the type of cells they come from. Most esophageal cancers develop from the inner lining (mucosa) of the esophagus. The lining of the esophagus is somewhat unique: it changes as it goes from the throat to the stomach. 

  • In the upper (proximal) esophagus, the lining of the esophagus looks like the lining of the throat. It is made up of squamous cells. So, when esophageal cancers start in this region, they are usually squamous cell carcinomas. 
  • In the lower (distal) esophagus, the more common type of cancer is called adenocarcinoma. These tumors develop from an area of the esophageal lining that contains glands.

In addition to invasive cancers, patients are sometimes diagnosed with precancerous lesions, called carcinoma-in-situ. These precancerous lesions can be seen prior to the development of either squamous cell carcinoma or adenocarcinoma of the esophagus. Carcinoma-in-situ occurs when the lining of the esophagus undergoes changes similar to cancerous changes without any invasion into the deeper tissues. While the cells themselves have cancer-like qualities, there has been no spread or invasion by the cancer cells. Another type of lesion that is considered to be a precursor to cancer itself is called Barrett's esophagus, which is explained below.

What causes esophageal cancer and am I at risk?

There are an estimated 18,440 new cases of esophageal cancer diagnosed each year. This represents about 1% of all cancer in the US. However, esophageal cancer is more common in other parts of the world, including China, India, Iran, and southern Africa. Most individuals are diagnosed between the ages of 55 and 74. Esophageal cancer also impacts more men than women. 

Risk factors for esophageal cancer include smoking and alcohol use. Although both are thought to be independent risk factors (meaning they can cause cancer on their own, with smoking's risk being higher), it seems that when both are combined, there is an increased risk for the development of esophageal cancer. Thus, individuals that both smoke and drink heavily are at a much higher risk to develop esophageal cancer when compared to non-smokers and non-drinkers. 

Other risk factors for esophageal cancer include obesity, eating a diet high in processed meats, HPV, and certain workplace exposures to nitrosamines, asbestos fibers, and petroleum products. Achalasia, which is a condition where there is ineffective peristalsis (movement) in the esophagus, as well as caustic esophageal injury from lye ingestion, can increase the risk of esophageal cancer. Individuals with disordered eating, in particular, bulimia, may also be at higher risk for esophageal cancer.

Esophageal cancer may be associated with several genetic syndromes. These include: 

  • Tylosis with Non-epidermolytic Palmoplantar Keratoderma (PPK).
  • Howel Evans’ syndrome.
  • Familial Barrett’s esophagus.
  • Bloom syndrome.
  • Fanconi anemia.

If you have any of these syndromes, you will likely need earlier and more frequent screening for esophageal cancer. You may also want to talk with your healthcare team about genetic counseling and testing.

Barrett’s Esophagus

In recent years the number of adenocarcinomas has been on the rise. These are now the most common type of esophageal cancer seen. Adenocarcinomas of the esophagus tend to involve the lower part of the esophagus. Adenocarcinoma almost always arises in the setting of Barrett's esophagus. 

Barrett's esophagus is caused by chronic irritation due to stomach acid. This happens due to a defect in the lower esophageal sphincter, which separates the stomach from the esophagus. This sphincter is located at approximately the level of the diaphragm. When the sphincter is dysfunctional, acid can reflux, or pass from the stomach into the esophagus. This condition is commonly known as gastroesophageal reflux disease or GERD. This can result in heartburn, bloating, loss of appetite, and stomach pain. Additionally, some people complain of chronic cough from the reflux due to irritation of the voice box from the acid reflux. Patients with chronic GERD are at risk for developing Barrett's esophagus and thus are at higher risk for developing adenocarcinoma of the esophagus. It is not clear if GERD outside the setting of Barrett's esophagus increases the risk of esophageal cancer, though it appears a long or severe history of reflux may increase the risk of esophageal cancer. There are several conditions, which can cause or worsen GERD, including a condition known as a hiatal hernia, where portions of the stomach herniate or improperly move through the diaphragm into the chest, causing sphincter dysfunction and resulting reflux. Additionally, obesity, smoking, and certain foods such as coffee and chocolate may potentially worsen reflux.

Barrett's esophagus is diagnosed by endoscopy, which is a procedure that uses a fiberoptic camera to look down into the esophagus. A gastroenterologist usually performs this test and if any suspicious lesions are seen, they can be biopsied during the endoscopy. Adenocarcinoma of the esophagus is thought to develop from Barrett's esophagus due to further carcinogenic changes in the abnormal lining.

Certain genetic conditions that cause increased acid secretion, such as Zollinger-Ellison syndrome, may increase the risk of adenocarcinomas of the esophagus. Although pharmaceutical agents for the prevention of acid secretion (histamine blockers, proton pump inhibitors) can be effective for the prevention of GERD symptoms, there is no proof that they decrease the incidence of Barrett's esophagus. Surgical manipulation of the esophageal sphincter, making it more difficult for acid to reach the esophagus, may lead to regression, though again, this is unproven. The most important recommendation for someone with Barrett's esophagus is active monitoring (see more about monitoring recommendations in the screening section below).

How can I prevent esophageal cancer?

Because of the link between tobacco and alcohol use and esophageal cancer, avoiding these can reduce your risk of esophageal cancer. It is important to eat a balanced diet, avoiding processed meats. Try to maintain a healthy body weight and exercise regularly. If you are experiencing GERD symptoms, talk to your healthcare provider about treatment options to prevent developing Barrett’s esophagus.

What screening tests are used for esophageal cancer?

There are no screening recommendations and no specific screening test for squamous cell carcinoma of the esophagus. However, screening and surveillance is very important in patients with BE, to ensure that it does not progress to adenocarcinoma. It has been estimated that there is about a 0.2%-2% risk annually of someone with Barrett's esophagus developing esophageal cancer, or a 10% lifetime risk.

What are the signs of esophageal cancer?

The most common sign of esophageal cancer is trouble swallowing. This is called dysphagia. It is the sense that food is stuck in the throat or chest. You may also feel like you are choking. Swallowing may also become painful. Dysphagia can often lead to significant weight loss as well. Other symptoms include:

  • Pain or burning in the chest.
  • A cough that won’t go away.
  • Vomiting.
  • Hiccups.
  • Esophageal bleeding leading to black tarry stools and anemia (low red blood cell count).

How is esophageal cancer diagnosed?

Anyone with trouble swallowing as described above should have a workup to ensure the symptoms are not from esophageal cancer. Your provider will perform a physical exam and order diagnostic tests. Initial tests may include:

  • Barium swallow-During this procedure, you will swallow barium so the contours of your esophagus can be seen on x-rays. Generally, the esophagus is smooth. If there is a change in the smooth contour of the esophagus, this may suggest cancer. 
  • Endoscopy- An endoscope is a narrow, flexible tube with an attached tiny camera that allows a provider to see inside the esophagus. It is inserted down the throat and into the esophagus and eventually the stomach. Through endoscopy, the location of the abnormality, the presence or absence of bleeding, and the amount of obstruction can all be seen. A biopsy can also be performed during endoscopy. Once a biopsy is performed, the pathologist can determine if there is esophageal cancer, and whether it is adenocarcinoma or squamous cell carcinoma.
  • Endoscopic ultrasound-(can also be performed during endoscopy) This can help the provider in determining the size of the tumor as well as if nearby lymph nodes are involved. 

Your provider may also order other tests to assist in the diagnosis of esophageal cancer including a CT scan, MRI, and/or PET scan to evaluate if the cancer has spread as well as blood tests to check for anemia and liver functioning. 

How is esophageal cancer staged?

After all of these tests are performed, the stage of the cancer can be determined. The staging of a cancer describes how much cancer has grown within the esophagus as well as whether it has spread. This is extremely important in terms of what treatment is offered to each individual patient. The staging system used to describe esophageal tumors is the "TNM system", as described by the American Joint Committee on Cancer. The TNM systems are used to describe many types of cancers. They have three components

  • T-describes the size/location/extent of the "primary" tumor in the esophagus.
  • N-describes if the cancer has spread to the lymph nodes
  • M-describes if the cancer has spread to other organs (i.e.-metastases). 

The staging for esophageal cancer also includes G-histologic grade (how the cells appear under the microscope). The location of the tumor is also considered in squamous cell esophageal cancers. The T, N, M, and G are combined to come up with a stage from 0-IV, with IV being the most advanced. 

The staging system is very complex. The entire staging system is outlined at the end of this article. Though complicated, the staging system helps healthcare providers determine the extent of the cancer, and in turn, make treatment decisions for your cancer. 

How is esophageal cancer treated?

The treatment plan for esophageal cancer depends on two main factors: the extent of the cancer and the general, baseline health of the individual. In people who have a very early-stage disease that has not spread to lymph nodes or deep into the esophagus, surgery alone may be appropriate. Some very early tumors, limited to the submucosa (the superficial layer of the esophagus), may be treated with endoscopic resection.

However, most people present with advanced-stage disease because symptoms often develop only after the tumor has grown to a large size or has spread. As a result, there is often a large amount of tumor present before cancer treatment can even begin. 

There are a number of different modalities that can be used to treat esophageal cancer including surgery, radiation, and chemotherapy. However, in people who can tolerate it, combined treatment of surgery, radiation, and chemotherapy is preferred.

Surgery

Surgery, including removing the esophagus (called an esophagectomy), is a very aggressive procedure. You need to be in good health to be able to have this procedure.

In general, the esophagus is removed by using either an incision through the ribs and abdomen or the neck and abdomen. When the esophagus is removed, the stomach is pulled up into the chest to keep the passageway for food intact. Not only is there a risk of infection and bleeding from the surgery itself, but the recovery period after surgery can be difficult. There is the risk of a leak forming at the new connection that is formed between the stomach and the remaining part of the esophagus (known as an anastamosis). This can result in further surgery and potentially lead to very serious complications. 

In advanced esophageal cancer, there is still a high failure rate with surgery alone. These failures occur both locally (in the region of the primary tumor or regional lymph nodes) or distantly (from metastatic spread of cancer through the bloodstream). Many studies have looked into adding chemotherapy and radiation therapy to esophagectomy in an attempt to improve outcomes. Though the results of these studies are somewhat mixed, it is thought that both radiation and chemotherapy add a benefit. Therefore, radiation therapy (for local tumor control) and chemotherapy (for distant control as well as to improve the effectiveness of radiation therapy) is almost always recommended either before or after the surgery.

Radiation

Radiation therapy uses high-energy x-rays to kill cancer cells. It does this by damaging the DNA in tumor cells. Normal cells in our body can repair radiation damage much quicker than cancer cells. While cancer cells are killed by radiation, many normal cells are not. This is the basis for the use of radiation therapy in cancer treatment. Radiation is delivered using large machines that produce high-energy x-rays. After radiation oncologists set up the radiation fields (the areas of the body that will be treated by radiation), treatment is begun. The number of treatments you may need will depend on your specific case. The treatment takes just a few minutes each day and is completely painless. It is designed to kill tumor cells in the area that is at risk to contain cancer cells, whether it is in the esophagus or the regional lymph nodes. Typical side effects mainly include a sore throat, skin irritation (resembling a sunburn), and fatigue.

Chemotherapy

Chemotherapy refers to medications to treat cancer that are usually given intravenously (IV, into a vein) or in pill form to take by mouth.  Chemotherapy travels throughout the bloodstream and throughout the body to kill cancer cells. This is one of the big advantages of chemotherapy. If cancer cells have broken off from the tumor and are somewhere else inside the body, chemotherapy has the chance of killing them, while radiation does not. 

The additional important benefit from chemotherapy in the treatment of esophageal cancer is that it works with radiation and as a result can kill more cancer cells. Similar to radiation, some normal cells are damaged during chemotherapy, resulting in side effects. The exact side effects depend on which type of chemotherapy is used, though fatigue, nausea, and a change in blood counts can result from commonly used chemotherapy agents.

There is some debate as to the optimal order in which to deliver these treatments to the esophagus. Different cancer treatment centers may vary the order in which they use these three types of therapies in the attempt to cure esophageal cancer. 

Many will use radiation therapy combined with chemotherapy pre-operatively (prior to surgery). The advantage of using chemotherapy and radiation together (called chemoradiation)  is that it often results in a decrease in the size of the tumor that needs to be removed. However, the toxicity from combining radiation with chemotherapy can cause more side effects than if given alone. It is very important for you to maintain your nutrition so you can be in your best health for surgery. Surgery usually takes place around 4-8 weeks after chemoradiation. Surgery after chemotherapy and radiation appears to improve the local control of the cancer growth further. 

Alternatively, some centers recommend post-operative (after surgery) treatment. The main advantage of this method is that surgery can be performed in an unirradiated field, allowing for a better surgical technique. Surgical removal of the entire tumor is ideal for the treatment of esophageal cancer.

In some cases, you may be too sick to undergo surgery or may choose not to undergo surgery. In these cases, a combined, concurrent (given at the same time) use of chemotherapy with radiation therapy is usually used. This method has been proven better than radiation alone. Lastly, some people are too sick to tolerate combined treatment and are treated with radiation or chemotherapy alone.

The combined use of radiation therapy and chemotherapy has toxicities as well; mainly irritation of the esophagus that can make it extremely painful and difficult to swallow. 

Medications commonly used in the treatment of esophageal cancers both before and after surgery, in combination with radiation or without surgery include paclitaxelcarboplatinfluorouracilcapecitabineoxaliplatincisplatinirinotecanleucovorin, and docetaxelNivolumab may be used in certain cases post-operatively. These medications are used in various combination regimens based on the staging and subtype of the cancer.

In more advanced, recurrent, or metastatic esophageal cancers, you may also be tested for certain biomarkers. These include HER2, MSI, MMR, NTRK, and PD-L1. The presence of these tumor markers may indicate the use of targeted therapy to treat the cancer. These medications include trastuzumabnivolumabramucirumabfam-trastuzumab deruxtecan-nxki, and pembrolizumab. These medications are often used in combination with the previously mentioned chemotherapy medications.

Supportive Care

Individuals with esophageal cancer also receive treatments to help alleviate symptoms associated with their disease if they cannot receive chemotherapy or radiation. Advanced esophageal cancer that is not curable can result in difficulty swallowing or being unable to swallow at all. Chest pain and bleeding are other common symptoms that can require palliation (link) (treatment to relieve symptoms). Radiation therapy is often used for palliation, with varying success; especially with obstruction - studies have reported improvement in swallowing in approximately 80% of patients. Mechanical stents can be placed, a "balloon" can be used to temporarily open the esophagus, or laser removal of the tumor can be attempted. These can achieve symptom relief quicker, though they have their risks and are only temporary measures.

As different treatments may be effective in treating a patient's cancer, it is good to be well-informed. Esophageal cancer is treated by a multidisciplinary team that includes medical oncologists, surgical oncologists, radiation oncologists, advanced practice providers, gastroenterologists, and nutritionists. The medical oncologist often leads the team with the goal to maximize the chance of cure and function after treatment.

Clinical Trials

Clinical trials are extremely important in furthering our knowledge of this disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your healthcare provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.

Follow-Up Care and Survivorship

Follow-up care after treatment for esophageal cancer varies greatly based on the stage of the tumor and the treatment(s) received. In general, you can expect frequent follow-up visits with your health care providers; typically, every 3-6 months for the first two years, then every 6-12 months for the next three years, and then annually. These follow-up visits may also include laboratory monitoring. For individuals with early-stage disease who were treated with endoscopic resection or ablation, you should have an upper endoscopy every 3 months for the first year, every six months for the second year, and then annually. Again, depending on the initial stage of disease and treatment you may also need imaging (CT scan of the chest and abdomen) as part of your follow-up care.

Fear of recurrence, ongoing swallowing and nutrition challenges, relationship changes and sexual health, the financial impact of cancer treatment, and employment issues are common emotional and practical issues experienced by esophageal cancer survivors. Your healthcare team can identify resources for support and management of these challenges faced during and after cancer.

Cancer survivorship is a relatively new focus of oncology care. With almost 17 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.

Resources for More Information

Esophageal Cancer Awareness Association: Offers help and advice to patients, caregivers, survivors, family members affected by the disease.

Esophageal Cancer Action Network (ECAN)

Appendix: Complete Esophageal Cancer Staging

American Joint Commission on Cancer (AJCC); 8th ed., 2017

T (Primary Tumor)

Description

TX

Primary tumor cannot be assessed

T0

No evidence of primary tumor

Tis

High-grade dysplasia, defined as malignant cells confined to the epithelium by the basement membrane

T1

Tumor invades the lamina propria, muscularis mucosae, or submucosa

T1a

Tumor invades the lamina propria or muscularis mucosae

T1b

Tumor invades the submucosa

T2

Tumor invades the muscularis propria

T3

Tumor invades adventitia

T4

Tumor invades adjacent structures

T4a

Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum

T4b

Tumor invades other adjacent structures, such as the aorta, vertebral body, or airway

 

N (Regional Lymph Nodes)

Description

NX

Regional lymph nodes cannot be assessed

N0

No regional lymph node metastasis

N1

Metastasis in one or two regional lymph nodes

N2

Metastasis in three to six regional lymph nodes

N3

Metastasis in seven or more regional lymph nodes

 

M (Distant Metastasis)

Description

M0

No distant metastasis

M1

Distant metastasis

 

G (Histologic Grade)

Description

GX

Grade cannot be assessed

G1 

Well-differentiated

G2

Moderately differentiated

G3

Poorly differentiated, undifferentiated

 

Location

Squamous Cell Carcinoma (only) Location Criteria*

X

Location unknown

Upper

Cervical esophagus to lower border of azygos vein

Middle

Lower border of azygos vein to lower border of inferior pulmonary vein

Lower 

Lower border of inferior pulmonary vein to stomach, including the gastroesophageal junction

*Location is defined by the position of the epicenter of the tumor in the esophagus

Squamous Cell Carcinoma Stage Grouping

Clinical Stage Grouping (cTNM)

cT

cN

M

Stage 0

T1s

N0

M0

Stage I

T1

N0-1

M0

Stage II

T2

T3

N0-1

N0

M0

M0

Stage III

T3

T1-3

N1

N2

M0

M0

Stage IVA

T4

Any T

N0-2

N3

M0

M0

Stage IVB

Any T

Any N

M1

 

Pathological Stage Grouping (pTNM)

pT

pN

M

G

Location

Stage 0

T1s

N0

M0

n/a

Any

Stage IA

T1a

T1a

N0

N0

M0

M0

G1

GX

Any

Any

Stage IB

T1a

T1b

T1b

N0

N0

N0

M0

M0

M0

G2-3

G1-2

GX

Any

Any

Any

Stage IIA

T2

T2

T3

T3

N0

N0

N0

N0

M0

M0

M0

M0

G2-3

GX

G1-3

G1

Any

Any

Lower

Upper/middle

Stage IIB

T3

T3

T3

T3

N0

N0

N0

N1

M0

M0

M0

M0

G2-3

GX

Any

Any

Upper/middle

Lower/upper/middle

Location X

Any

Stage IIIA

T1

T2

N2

N1

M0

M0

Any

Any

Any

Any

Stage IIIB

T2

T3

T4a

N2

N1-2

N0-1

M0

M0

M0

Any

Any

Any

Any

Any 

Any

Stage IVA

T4a

T4B

Any T

N2

N0-2

N3

M0

M0

M0

Any

Any

Any

Any

Any 

Any

Stage IVB

Any T

Any N

M1

Any

Any

 

Postadjuvant Therapy (ypTNM)* Stage Grouping

yPT

yPN

M

Stage I

T0-2

N0

M0

Stage II

T3

N0

M0

Stage IIIA

T0-2

N1

M0

Stage IIB

T3

T0-3

T4a

N1

N2

N0

M0

M0

M0

Stage IVA

T4a

T4a

T4b

Any T

N1-2

NX

N0-2

N3

M0

M0

M0

M0

Stage IVB

Any T

Any N 

M1

* y indicates a pre-operative treatment was given

Adenocarcinoma Stage Grouping

Clinical Stage Grouping (cTNM)

cT

cN

M

Stage 0

T1s

N0

M0

Stage I

T1

N0

M0

Stage IIA

T2

N1

M0

Stage IIB

T2

N0

M0

Stage III

T2

T3

T4a

N1

N0-1

N0-1

M0

M0

M0

Stage IVA

T1-4a

T4b

Any T

N2

N0-2

N3

M0

M0

M0

Stage IVB

Any T

Any N

M1

 

Pathological Stage Grouping (pTNM)

pT

pN

M

G

Stage 0

T1a

N0

M0

N/A

Stage IA

T1a

T1a

N0

N0

M0

M0

G1

GX

Stage IB

T1a

T1b

T1b

N0

N0

N0

M0

M0

M0

G2

G1-2

GX

Stage IC

T1

T2

N0

N0

M0

M0

G3

G1-2

Stage IIA

T2

T2

N0

N0

M0

M0

G3

GX

Stage IIB

T1

T3

N1

N0

M0

M0

Any 

Any

Stage IIIA

T1

T2

N2

N1

M0

M0

Any 

Any

Stage IIIB

T2

T3

T4a

N2

N1-2

N0-1

M0

M0

M0

Any

Any

Any

Stage IVA

T4a

T4b

Any T 

N2

N0-2

N3

M0

M0

M0

Any

Any

Any

Stage IVB

Any T

Any N

M1

Any

 

Postadjuvant Therapy (ypTNM)* Stage Grouping

yPT

yPN

M

Stage I

T0-2

N0

M0

Stage II

T3

N0

M0

Stage IIIA

T0-2

N1

M0

Stage IIB

T3

T0-3

T4a

N1

N2

N0

M0

M0

M0

Stage IVA

T4a

T4a

T4b

Any T

N1-2

NX

N0-2

N3

M0

M0

M0

M0

Stage IVB

Any T

Any N 

M1

* y indicates a pre-operative treatment was given

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July 6, 2021

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