Metastatic (stage 4) esophageal cancer

Stage 4 esophageal cancer, also called metastatic esophageal cancer, is cancer that starts in the esophagus and has spread to parts of the body outside the esophagus. In stage 4A, esophageal cancer has advanced through the wall of the esophagus and may be found in distant lymph nodes, but it has not spread to other organs. If the cancer has spread to other organs, such as the liver or lungs, it is considered stage 4B.

Metastatic esophageal cancer cannot be cured. But having metastatic cancer does not necessarily mean that death is near. Treatment can help control the cancer, relieve symptoms, improve quality of life and help some people live longer. Treatment may include chemotherapy, immunotherapy, targeted therapy, radiation therapy and supportive care. If treatment is no longer slowing or controlling the cancer, care may focus more on comfort and quality of life.

Types

The two main types of esophageal cancer are adenocarcinoma and squamous cell carcinoma. They develop from different types of cells and are more common in different parts of the esophagus.

• Adenocarcinoma begins in mucus-making glandular cells and most often develops in the lower part of the esophagus, near the stomach.
• Squamous cell carcinoma begins in thin, flat cells that line the esophagus. It is more common in the upper and middle parts of the esophagus but can occur anywhere in the esophagus.

The type of esophageal cancer you have can affect treatment. Cancer cells also may have features that help guide treatment. These features are called biomarkers. Certain tests may help the healthcare team choose targeted therapy or immunotherapy.

Symptoms of metastatic esophageal cancer can come from the cancer in the esophagus or from cancer that has spread to other parts of the body. Trouble swallowing and weight loss are common symptoms.

Other symptoms may include:

• Pain when swallowing.
• Pain behind the breastbone.
• Hoarseness or cough.
• Indigestion or heartburn.
• Food or liquid coming back up after swallowing.
• A lump under the skin or swollen lymph nodes.
• Bleeding in the upper digestive tract.

Symptoms also can depend on where the cancer has spread. Cancer in the lungs may cause shortness of breath. Cancer in the liver may cause yellowing of the skin and eyes, called jaundice, or swelling in the abdomen. Cancer in the bones may cause pain or broken bones. Cancer in the brain may cause headaches, seizures or dizziness.

End-of-life symptoms

Near the end of life, symptoms may change as the body slows down. These changes can happen with many advanced cancers and are not specific to esophageal cancer. Changes in the last weeks and days of life may include:

• Increasing tiredness, drowsiness and weakness.
• Less interest in food and drinks.
• Shortness of breath.
• Trouble swallowing.
• Increasing confusion or decreased awareness.
• Less urine output.
• Changes in breathing, including periods when breathing stops and starts.

No single symptom can predict exactly how much time a person has left. The healthcare team can help manage symptoms and talk with the person and family about what to expect.

When to seek care

Tell your healthcare team about worsening trouble swallowing or other symptoms that make it hard to eat or drink.

Metastatic esophageal cancer develops when cancer cells break away from the original tumor and spread to other parts of the body. The cells may spread through nearby tissue, the lymphatic system or the bloodstream.

It isn't well known why some esophageal cancers spread and others do not. Cancer cells go through several steps before they can form a tumor in another part of the body.

Certain factors raise the risk of developing esophageal cancer, and the risk factors differ by the type of cancer.

Risk factors for squamous cell carcinoma include:

• Smoking.
• Heavy alcohol use.

Risk factors for adenocarcinoma include:

• Gastroesophageal reflux disease (GERD).
• Barrett's esophagus.
• Obesity.

Metastatic esophageal cancer can cause complications from the tumor in the esophagus or from cancer that has spread to other parts of the body.

Complications may include:

• Trouble swallowing that makes it hard to eat or drink.
• Weight loss and malnutrition.
• Bleeding in the esophagus or upper digestive tract.
• Bone pain or broken bones when cancer has spread to the bones.
• Shortness of breath or fluid buildup around the lungs.
• Jaundice or fluid buildup in the abdomen, called ascites, when the liver is affected.
• Headaches, dizziness or seizures when cancer has spread to the brain.

Esophageal cancer usually is diagnosed with an upper endoscopy and biopsy. During an upper endoscopy, a thin, flexible tube with a camera is used to look inside the esophagus. A tissue sample, called a biopsy, can be removed and tested for cancer.

After esophageal cancer is diagnosed, more tests may be used to find out how far it has spread and to help plan treatment.

Tests may include:

• Imaging tests. CT and PET/CT scans can help show where the cancer has spread. Other imaging tests, such as MRI, may be used in some situations.
• Endoscopic ultrasound. This test uses sound waves to make detailed images of the esophagus and nearby lymph nodes. It may be used when the healthcare team needs more information about how far the cancer has spread.
• Biopsy of an area where cancer has spread. A tissue sample from another part of the body may be tested when needed to confirm that the cancer has spread.

Tumor tissue also may be tested for certain features that can help guide treatment. These features, called biomarkers, may help show whether targeted therapy or immunotherapy is likely to help.

Treatment for metastatic esophageal cancer focuses on slowing or controlling the cancer, helping people live longer and relieving symptoms. The treatment plan depends on the type of esophageal cancer, where it has spread, a person's overall health and results of tests on the tumor.

Treatment for metastatic esophageal cancer has changed in recent years. Immunotherapy now is used for some people, either with chemotherapy or with another immunotherapy medicine. Testing the tumor also can identify features that may be treated with targeted medicines. These treatment options and test results can help the healthcare team choose treatment based on the type of cancer and its test results.

Chemotherapy

Chemotherapy uses medicines to kill cancer cells or slow their growth. It may be used alone or as part of a combination treatment for metastatic esophageal cancer.

Immunotherapy

Immunotherapy helps the immune system recognize and attack cancer cells. Some medicines that fall into this class include pembrolizumab (Keytruda), nivolumab (Opdivo) and ipilimumab (Yervoy). Which immunotherapy is used depends on the type of esophageal cancer and results of tumor testing. When a person has the right markers for these medicines, these treatments have improved survival compared with chemotherapy alone in large studies.

Targeted therapy

Targeted therapy uses medicines that attack specific features of cancer cells.

Some esophageal adenocarcinomas have high levels of a protein called HER2, which can help cancer cells grow. These cancers are called HER2 positive. HER2-positive cancers may be treated with a HER2-targeted medicine along with chemotherapy and, in some cases, immunotherapy.

Radiation therapy

Radiation therapy may be used to shrink tumors, relieve pain or make swallowing easier. It also may be used to treat selected areas where the cancer has spread.

Proton beam therapy is one type of radiation therapy. It can reduce radiation exposure to some nearby healthy tissues compared with traditional photon radiation. Most studies of proton beam therapy for esophageal cancer have involved localized or locally advanced disease, so its role in metastatic esophageal cancer is less clear.

Treatments to help with swallowing

If a tumor narrows the esophagus, treatment may be needed to make swallowing easier. Options may include radiation therapy, an esophageal stent or other procedures performed through an endoscope.

Palliative care

Palliative care is specialized care that focuses on easing symptoms and improving quality of life. It can be given at the same time as treatments intended to control the cancer. Early palliative care may help with symptoms, nutrition, emotional distress and decisions about treatment.

If you have metastatic esophageal cancer, you may need help managing issues such as pain, nausea, trouble eating, weight loss or bleeding. Palliative care specialists work with the cancer care team to help manage these issues and support you and your family throughout treatment.

Surgery

Surgery usually is not used to treat widespread metastatic esophageal cancer. For some people whose cancer has spread to only a few areas, surgery or another treatment such as radiation to those areas may be an option after treatment with medicines. Ask your healthcare team if surgery has a role in your care.

Clinical trials

Clinical trials are studies of new treatments. They can be an important part of care for people with metastatic esophageal cancer. Trials may study new medicines, new treatment combinations or treatments aimed at specific features of cancer cells. Ask your healthcare team whether a clinical trial may be an option for you.

Living with metastatic esophageal cancer can make eating and drinking difficult. Trouble swallowing can lead to weight loss and malnutrition.

These steps may help:

• Choose foods and drinks that are easier to swallow.
• Eat smaller meals more often if large meals are difficult.
• Tell your healthcare team if swallowing becomes harder or if you are losing weight.
• Ask whether a dietitian can help you find foods and drinks that provide enough calories and protein.
• Report new or worsening pain, shortness of breath, vomiting, or other symptoms so they can be treated.

Living with metastatic esophageal cancer can be difficult for both the people with cancer and those close to them. Support can help with emotional concerns, practical needs and decisions about care.

Palliative care can help manage symptoms and support quality of life at any point during treatment. It also can help with communication about treatment goals and care preferences.

Support also may come from family, friends, social workers, counselors, spiritual care professionals and cancer support groups.

Mayo Clinic Connect offers an online community where people affected by esophageal cancer can share experiences and support one another. Hearing from others living with esophageal cancer may help you feel less alone. You also can learn how others have handled treatment and day-to-day challenges.

Before an appointment, write down your questions and any changes you have noticed. Consider bringing someone with you to listen and take notes.

What you can do

Bring information that may help your healthcare team understand how you are doing. This may include:

• A list of medicines, vitamins and supplements you take.
• A list of new or worsening symptoms.
• Notes about side effects from treatment.
• Changes in your weight or ability to eat and drink.
• Results of tumor or genetic testing done elsewhere.
• Your most important questions.

Questions you may want to ask include:

• Where has my cancer spread?
• What is the goal of treatment?
• What treatments are reasonable for me?
• What benefit might I expect from treatment?
• What side effects are most important to know about?
• How will we know whether treatment is working?
• What do my tumor test results mean for treatment?

Additional questions may include:

• Could targeted therapy or immunotherapy be an option for me?
• Is there a clinical trial I could consider?
• What can be done if swallowing becomes more difficult?
• Who should I call if my symptoms get worse?
• Can palliative care help me now?
• Can you help me understand my prognosis based on my health and how the cancer is responding?

What to expect from your doctor

Your healthcare team may ask about:

• Trouble swallowing and how much you are able to eat and drink.
• Weight loss.
• Pain or other symptoms.
• Side effects from treatment.
• Your ability to carry out daily activities.
• Your priorities and goals for care.

Tell your healthcare team what matters most to you. Your goals and preferences can help guide treatment decisions.

Stage 4 esophageal cancer is divided into stage 4A and stage 4B based on how far the cancer has spread.

• Stage 4A. The cancer has spread extensively in or through the esophagus or to many nearby lymph nodes. It has not spread to distant organs.
• Stage 4B. The cancer has spread to distant parts of the body, such as the liver or lungs.

The stage is one factor the healthcare team uses to plan treatment. Other factors include the type of esophageal cancer, overall health and results of tests on the tumor.

For stage 4A, treatment may focus on the cancer in and around the esophagus. Treatment may include chemotherapy, radiation therapy and sometimes surgery.

For stage 4B, treatment usually focuses on slowing or controlling cancer throughout the body, helping people live longer and relieving symptoms. Treatment may include chemotherapy, immunotherapy, targeted therapy, radiation therapy and supportive care. Surgery usually is not used for widespread metastatic disease.

Survival rates can give information about prognosis, also called outlook, and life expectancy. These numbers are based on groups of people. They cannot predict how long one person will live.

The National Cancer Institute collects cancer statistics from across the United States. For esophageal cancer that has spread to distant parts of the body, the estimated survival rates are:

What affects survival?

Many factors can affect survival with metastatic esophageal cancer. These include treatment, age, the type of esophageal cancer, where it has spread, overall health and how the cancer responds to treatment.

Treatment

Treatment can help some people with metastatic esophageal cancer live longer. In one large study, half of the people who received pembrolizumab plus chemotherapy lived at least 12.3 months. Half of those who received chemotherapy alone lived at least 9.8 months. At five years, about 11% of people who received pembrolizumab plus chemotherapy were alive, compared with 3% of those who received chemotherapy alone.

There is no single estimate for how long someone will live without treatment. In one study, half of the people who received supportive care alone lived about four months or longer. Half of those who received chemotherapy plus supportive care lived about nine months or longer. Most people in the study had squamous cell carcinoma, so these results may not apply to everyone with metastatic esophageal cancer.

Age

Age also may affect survival. In one study, half of the people diagnosed before age 50 lived at least seven months. Half of those diagnosed at age 50 or older lived at least five months. Younger people still had somewhat better survival after researchers accounted for other differences between the groups.

Where the cancer has spread

Where the cancer has spread also may affect survival. In one study of people younger than 50, half lived at least:

• Seven months with cancer that had spread to the liver.
• Eight months with cancer that had spread to the lungs.
• Five months with cancer that had spread to the bones.
• Six months with cancer that had spread to the brain.

Among people age 50 and older, half lived at least four months when the cancer had spread to the bones, liver or lungs. Half lived at least six months when it had spread to the brain.

These numbers are estimates from groups of people diagnosed from 2010 through 2020. They cannot predict one person's life expectancy.

Reliable life expectancy estimates aren't available for many less common sites of spread, such as the thyroid or breast.

Can metastatic esophageal cancer go into remission?

Some people with metastatic esophageal cancer have a strong response to treatment. The cancer may shrink a lot or may not be seen on tests for a time. Clinical studies call this a complete response.

A complete response does not mean the cancer is cured. At later stages, esophageal cancer can be treated but rarely can be cured.