Early Detection, Diagnosis, and Staging of Esophageal Cancer

Experts often recommend that people with Barrett’s esophagus get regular upper endoscopies. For this test, the doctor looks at the inside of the esophagus through a flexible lighted tube called an endoscope. (See Tests for esophageal cancer below.) The doctor may remove (biopsy) small samples of tissue from the abnormal area so that they can be checked for dysplasia (precancer cells) or cancer cells.

Doctors aren’t certain how often the test should be repeated, but most recommend testing more often if areas of dysplasia are found. This testing is repeated even more often if there is high-grade dysplasia (cells that appear very abnormal).

If the area of Barrett’s esophagus is large and/or there is high-grade dysplasia, treatment of the abnormal area might be advised because of the high risk that esophageal cancer (adenocarcinoma) is either already present (but was not found) or will develop within a few years. Treatment options for high-grade dysplasia might include:

• Endoscopic mucosal resection (EMR)
• Radiofrequency ablation (RFA)
• Endoscopic cryoablation
• Photodynamic therapy (PDT)

For more on these procedures, see Endoscopic Treatments for Esophageal cancer.

People with certain inherited syndromes (sometimes called hereditary syndromes) have an increased risk of developing esophageal cancer. Examples include:

• Tylosis (Howel-Evans syndrome)
• Bloom syndrome
• Fanconi anemia
• Familial Barrett’s esophagus

Because of the increased risk, these people might need frequent endoscopies to look for cancer or precancer. For example, doctors might recommend that they start getting regular upper endoscopies at a younger age.

If you have one of these inherited syndromes, talk with your doctor about cancer screening and what is right for you.

This test, also known as an esophagogastroduodenoscopy or EGD, is an important test for diagnosing esophageal cancer. During an upper endoscopy, you are sedated (made sleepy) and then the doctor passes an endoscope down your throat to look at the inner wall of the esophagus, stomach, and the first part of the small intestine. The endoscope's camera is connected to a monitor, which lets the doctor see any abnormal areas in the wall of the esophagus clearly.

The doctor can use special instruments through the endoscope to remove (biopsy) tissue samples from any abnormal areas. These samples are sent to the lab to check if they contain cancer and possibly for other tests (see below).

If cancer is making it hard for food or liquids to pass through the esophagus, certain instruments can be used to help enlarge the opening.

Upper endoscopy can give the doctor important information about the size and spread of the tumor. This can be used to help determine the stage of the cancer, which can inform a person’s treatment options.

This test is usually done at the same time as an upper endoscopy. For an EUS, a probe that gives off sound waves is at the end of an endoscope. This allows the probe to get very close to tumors in the esophagus, as well as to nearby structures outside the esophagus wall.

This test can be very useful in determining the size of an esophageal cancer and how far it has grown into the esophagus wall and into nearby structures.

EUS can also help show if nearby lymph nodes might be affected by the cancer. If enlarged lymph nodes are seen on the ultrasound, the doctor can pass a thin, hollow needle through the endoscope to get biopsy samples of them (known as an endoscopic ultrasound-guided fine needle aspiration, or EUS-FNA). This can help determine the stage of the cancer and determine a person’s treatment options.

During a bronchoscopy, a special type of endoscope called a bronchoscope is put in through your nose or mouth, down your throat, into your trachea (windpipe), and into the airways (bronchi and bronchioles) of your lungs.

This exam is sometimes done as part of the workup for cancer in the upper part of the esophagus to see if it has spread to the upper airways (trachea or bronchi), which are right in front of the esophagus.

These exams are sometimes done to let the doctor see and get biopsy samples from lymph nodes and other organs near the esophagus inside the chest (by thoracoscopy) or the abdomen (by laparoscopy).

These procedures are done in an operating room while you are under general anesthesia (in a deep sleep). A small cut is made in the side of the chest wall (for thoracoscopy) or the abdomen (for laparoscopy). Sometimes more than one cut is made. The doctor then inserts a scope through the incision to view the space around the esophagus. The doctor can pass thin tools into the space to remove lymph nodes and biopsy samples to see if the cancer has spread. This information can be used to help decide whether a person is likely to benefit from surgery.

Esophageal cancer cells might be tested to see if they show high levels of gene changes called microsatellite instability (MSI-H) or if they have changes in any of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2). They might also be checked to see if they have a high tumor mutational burden (TMB-H). This would mean that the cancer is more likely to respond to treatment with an immunotherapy drug.

Your biopsy sample may be tested for the HER2 gene or protein. In some people, esophageal cancer cells have too much HER2, a protein that helps them grow. Drugs that target the HER2 protein may help treat these cancers. See Targeted Drug Therapy for Esophageal Cancer for more information.

More advanced cases of esophageal cancers may be tested to see how much of the PD-L1 protein the cancer cells have. Higher levels of PD-L1 mean the cancer is more likely to be helped by treatment with immunotherapy.

Higher levels of a protein called CLDN18.2 in esophageal cancer cells mean that certain drugs targeting CLDN18.2 might be helpful.

The cancer cells might also be tested for changes in other genes, such as NTRK, BRAF, and RET. For more advanced cancers that have one of these gene changes, drugs that target the proteins coded for by the gene might be helpful.

Testing for many of these changes is now often done with next-generation sequencing (NGS). This type of test can sequence the genetic material (DNA and/or RNA) of cancer cells to look for mutations or other changes that might help guide treatment. NGS testing usually takes a week or longer to get results.

If you're having trouble swallowing, sometimes a barium swallow might be the first test done. In this test, you will be asked to swallow a chalky liquid called barium sulfate. This coats and outlines the inner walls of the esophagus when x-rays are taken.

This test can be done by itself, or as a part of a series of x-rays called an upper gastrointestinal (GI) series, that includes the stomach and part of the small intestine.

A barium swallow can show any abnormal areas in the smooth inner lining of the esophagus. It can sometimes show even small, early cancers, which can look like small round bumps or flat, raised areas (called plaques). More advanced cancers often look like large irregular areas and can cause narrowing of the inside of the esophagus.

While this test can sometimes be helpful, it has some limits. It can’t be used to sample (biopsy) tissue from the esophagus, so it can’t tell for sure if someone has esophageal cancer (or what type it is). Nor can it tell how deeply a cancer has invaded into the esophagus wall. Because of this, upper endoscopy (described above) is often the first test done if esophageal cancer is suspected.

A barium swallow can sometimes be used to diagnose one of the more serious complications of esophageal cancer, called a tracheo-esophageal fistula. This occurs when the tumor destroys the tissue between the esophagus and the trachea (windpipe), which is right in front of it, creating a hole connecting them. Anything that is swallowed can then pass from the esophagus into the windpipe and lungs (known as aspiration). This can lead to frequent coughing, gagging, or even pneumonia. This problem can be helped with surgery or an endoscopy procedure.

A CT scan uses x-rays to make detailed cross-sectional images of your body.This test can help tell if esophageal cancer has spread to nearby organs and lymph nodes (bean-sized collections of immune cells to which cancers often spread first) or to distant parts of the body.

CT-guided needle biopsy: If a suspected area of cancer is deep within your body, a CT scan might be used to help guide a biopsy needle into this area to get a tissue sample to check for cancer.

Like CT scans, MRI scans show detailed images of soft tissues in the body. But MRIs use radio waves and strong magnets instead of x-rays. MRI isn’t used as often as CT scans for esophageal cancer.

For a PET scan, a slightly radioactive form of sugar (known as FDG) is injected into the blood and collects mainly in cancer cells. These areas of radioactivity can be seen on a PET scan using a special camera. The pictures from a PET scan aren’t as detailed as CT or MRI images, but they can often show areas of cancer anywhere in the body.

PET/CT scan: Sometimes a PET scan is combined with a CT scan using a special machine that can do both at the same time. This lets the doctor compare areas of higher radioactivity on the PET scan with the more detailed picture of that area on the CT scan.

A PET/CT scan can often be useful if your doctor thinks the cancer might have spread to other parts of the body but doesn’t know where.

This test measures the different types of cells in your blood. It can show if you have anemia (too few red blood cells). Some people with esophageal cancer have low red blood cell counts because the tumor has been bleeding into the digestive tract.

These tests can help show how well the liver and kidneys are working, as well as measure the levels of certain minerals in the blood.