Oesophageal Squamous Cell Carcinoma

Oesophageal squamous cell carcinoma is a type of cancer that affects the esophagus, the muscular tube connecting your throat to your stomach. This form of cancer usually develops in the upper or middle part of the esophagus and often remains undetected until advanced stages, making early recognition and proper treatment critical.

Table of contents

• Medical Classification and Terminology
• Associated Anatomy
• What Is Oesophageal Squamous Cell Carcinoma
• Who Is Affected
• Signs and Symptoms
• Risk Factors and Causes
• How It Is Diagnosed
• Stages of the Disease
• Treatment Options
• Outlook and Survival
• Reducing Your Risk

Medical Classification and Terminology

ESCC, Esophageal epidermoid carcinoma, Esophageal squamous cell carcinoma, Squamous cell carcinoma of the esophagus

C15.0; C15.1; C15.3; C15.4

2B70.1

10061534

Associated Anatomy

• Esophagus

Oesophageal squamous cell carcinoma develops in the esophagus, the hollow, muscular tube that moves food and liquid from your throat to your stomach^[1]. The wall of the esophagus is made up of several layers of tissue, including the inner lining called mucosa, muscle layers, and connective tissue^[6].

What Is Oesophageal Squamous Cell Carcinoma

Oesophageal squamous cell carcinoma is a type of esophageal cancer that can affect any part of the esophagus, though it is usually located in the upper or middle third^[5]. This cancer begins in the thin, flat cells called squamous cells that line the inside of the esophagus^[1][6].

Esophageal cancer happens when cancerous cells in your esophageal tissue begin to multiply, eventually creating a tumor. The cancer is aggressive, but many people don’t notice symptoms until after the cancer has spread^[1]. This is because the esophagus is very flexible and stretches to make room for large bites of food. As the tumor grows, it starts to block the esophagus opening, making it difficult to swallow^[1].

There are two main types of esophageal cancer. Squamous cell carcinoma forms in the squamous cells lining the esophagus and usually affects the upper and middle parts. In contrast, adenocarcinoma develops in glandular cells that produce mucus and typically affects the lower part of the esophagus near the stomach^[1][6].

Who Is Affected

Esophageal cancer is the 10th most common cancer in the world, and approximately 90% of esophageal cancers worldwide are squamous cell carcinoma^[1][4]. In 2020, there were 604,000 new cases globally and 544,000 related deaths^[4].

The prevalence varies significantly by geographic region. The highest prevalence of squamous cell carcinoma is found in the esophageal cancer belt, which includes parts of northern Iran, central Asia, and China. It is also more commonly found in Africa, Asia, and parts of Eastern Europe^[4][5]. In Western countries like the United States and Western Europe, adenocarcinoma is more common^[4].

The average age of onset is between 60 and 70 years, and it is more frequently seen in males^[5]. In the United States, people who are Black and people who are Asian with esophageal cancer usually have squamous cell carcinoma, while people who are white are more likely to have adenocarcinoma^[1].

Oesophageal squamous cell carcinoma has an estimated annual incidence of 1 in 29,400^[5].

Signs and Symptoms

Oesophageal squamous cell carcinoma is usually asymptomatic until an advanced disease stage, which means many people don’t notice any problems early on^[5]. Difficulty swallowing, called dysphagia, is typically the first symptom people may notice. This usually begins with difficulty swallowing solid foods and then progresses to difficulty with liquids^[1][5].

Common symptoms include^[1][5][6]:

• Painful or difficult swallowing
• Unintentional weight loss
• Pain behind the breastbone or between the shoulder blades
• Pain in your throat or back
• Heartburn
• Hoarseness or chronic cough
• Vomiting or coughing up blood

Less commonly, odynophagia (painful swallowing) or chest pain can be presenting features^[5].

Esophageal cancer typically grows very rapidly. Because the esophagus is flexible and expands around the tumor as it grows, people often don’t have symptoms until the cancer has spread^[1].

Risk Factors and Causes

The exact cause of oesophageal squamous cell carcinoma is unknown^[5]. However, healthcare providers have identified several risk factors that increase the chance of developing this cancer.

The principal risk factors are cigarette smoking and alcohol abuse^[5][6]. Tobacco use, including smoking and using smokeless tobacco, significantly increases risk. Chronic and heavy use of alcohol also raises the risk considerably^[1][6].

Additional risk factors include^[1][5][20]:

• Being overweight or having obesity, which may cause inflammation in the esophagus
• Idiopathic achalasia, a motility disorder of the esophagus
• Chewing betel quid or areca nut
• Drinking very hot beverages, such as hot coffee, tea, or maté at temperatures higher than 65°C
• Diets high in processed meats
• Infection with certain types of human papillomavirus (HPV), a common sexually transmitted disease contracted through oral sex
• Older age

It’s important to note that Barrett’s esophagus and gastroesophageal reflux disease (GERD), which involve stomach acid backing up into the esophagus, are primarily linked to adenocarcinoma rather than squamous cell carcinoma of the esophagus^[1].

How It Is Diagnosed

Tests that examine the esophagus are used to diagnose oesophageal squamous cell carcinoma^[6]. The diagnostic process typically includes several steps.

A physical exam and health history are conducted first to check general signs of health and look for any unusual signs. A history of the patient’s health habits, past illnesses, and treatments is also taken^[6].

A barium swallow study may be performed, which uses X-rays to look at the digestive system. Before the test, you drink a white liquid called barium that coats your esophagus and makes it easier to see on X-rays. This can show changes in the esophagus, such as a growth that could be cancerous^[8].

Esophagoscopy or upper endoscopy is a key diagnostic procedure. This involves inserting a thin, flexible tube with a camera at the end, called an endoscope, through the mouth or nose and down the throat into the esophagus. The healthcare professional looks for abnormal areas^[6][8].

A biopsy is essential to establish the diagnosis. During endoscopy, the healthcare professional uses special cutting tools passed through the endoscope to remove a very small amount of tissue from the inside of the esophagus. This tissue sample is sent to a laboratory to look for cancer cells^[5][8].

Once cancer is diagnosed, additional tests help determine how far the cancer has spread. A computed tomography (CT) scan of the neck, chest, and abdomen can identify the primary tumor and any spread to the lymph nodes and organs such as the liver, lungs, and bone^[5]. CT combined with a positron emission tomography scan (CT-PET) may also be used^[5].

Endoscopic ultrasound (EUS), which combines an ultrasound probe with an endoscope, is increasingly used for staging and is particularly valuable for early cancers^[5]. In upper or mid-esophageal tumors where there is a possibility of invasion of the airway, a bronchoscopy may be required^[5].

Stages of the Disease

Squamous cell carcinoma of the esophagus is staged differently than adenocarcinoma^[2]. The most common staging system is the TNM system, which stands for tumor, node, and metastasis. It describes the size of the primary tumor, whether the cancer has spread to the lymph nodes, and whether it has spread to another part of the body^[2][3].

There are five main stages: stage 0 followed by stages 1 to 4. Generally, the higher the stage number, the more the cancer has spread^[2]. The stage also depends on the grade of the cancer, which describes how abnormal the cells look under the microscope. Grades range from 1 (low grade, looking most like normal cells) to 3 (high grade, looking very abnormal)^[2][3].

The stages are defined as follows^[2]:

Stage 0 (carcinoma in situ): The tumor is only within the inner lining of the esophagus. Doctors may describe it as high-grade dysplasia, which is a precancerous condition.

Stage 1A: The tumor has grown into the connective tissue or muscle layer of the mucosa and is low grade.

Stage 1B: The tumor has grown into the connective tissue or muscle layer of the mucosa and is moderate or high grade, or it has grown into the layer of connective tissue that surrounds the mucosa and is any grade, or it has grown into the thick outer muscle layer and is low grade.

Stage 2A: The tumor has grown into the outer muscle layer and is moderate or high grade and located anywhere along the esophagus, or it has grown into the outermost layer of connective tissue and is any grade and located in the lower esophagus, or it has grown into the outermost layer, is low grade, and located in the middle or upper part.

Stage 2B: The tumor has grown into the outermost layer and is moderate or high grade and located in the middle or upper part, or it has grown into the outermost layer and the grade or location cannot be determined, or the tumor is smaller but has spread to 1 or 2 nearby lymph nodes.

Stage 3A: The tumor has grown into early layers or the submucosa and has spread to 3 to 6 nearby lymph nodes, or it has grown into the outer muscle layer and has spread to 1 or 2 nearby lymph nodes.

Stage 3B: The tumor has grown into the outer muscle layer and has spread to 3 to 6 nearby lymph nodes, or it has grown into the outermost layer and has spread to 1 to 6 nearby lymph nodes, or the tumor has grown into nearby areas and may have spread to 1 or 2 nearby lymph nodes.

Stage 4: The cancer has spread to distant parts of the body.

Treatment Options

Treatment of oesophageal squamous cell carcinoma varies according to the stage of the disease and whether it can be removed surgically^[4][7]. Treatment decisions should be made in an interdisciplinary tumor board and based on informed patient wishes^[7].

Early-Stage Disease

Patients with early oesophageal squamous cell carcinoma should undergo an endoscopic resection^[7][11]. Endoscopic therapy is suitable for high-grade dysplasia and small tumors. Techniques include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD)^[11].

If the edges of the removed tissue contain tumor cells or other risk factors for lymph node spread are present, further surgery to remove part or all of the esophagus should be offered^[7][13].

Surgery

The traditional treatment of oesophageal squamous cell carcinoma is surgical removal, called esophagectomy^[5]. Different surgical approaches can be used, including transthoracic resection, transhiatal esophagectomy, and increasingly, minimally invasive approaches^[5][11].

Sometimes surgery involves removing part of the esophagus and the top part of the stomach, called an oesophagogastrectomy^[12]. For reconstruction after surgery, a gastric conduit is preferred^[11].

Locally Advanced Disease

In a locally advanced setting, radiochemotherapy (a combination of radiation therapy and chemotherapy) with or without surgery remains the standard of care^[7]. The standard treatment approach for locally advanced, resectable disease is currently chemoradiation with or without surgery^[4].

There is increasing use of chemotherapy or the combination of chemotherapy and radiotherapy before and after surgery, particularly where the tumor is locally advanced^[5]. The typical chemotherapy regimen is a combination of a platinum drug with a fluoropyrimidine or paclitaxel, though different regimens are being evaluated^[4].

In the absence of complete response after chemoradiation and successful removal of all visible cancer, adjuvant immunotherapy for one year should be administered to improve disease-free survival^[7].

Metastatic Disease

In metastatic first-line setting, a combination of platinum and fluoropyrimidine-based chemotherapy with checkpoint inhibitors (a type of immunotherapy) is the novel standard of care^[7]. Immunotherapy has also been approved in second-line settings^[7].

When healthcare providers can’t cure the cancer, they focus on helping people live longer, easing symptoms, and maintaining quality of life^[1]. Treatments to control symptoms may include radiation therapy or other palliative procedures^[1][12].

With the landscape of immunotherapy rapidly evolving, targeted agents and immunotherapy are at the forefront of new treatments for oesophageal squamous cell carcinoma^[4]. Ultimately, the treatment approach should be individualized to each patient^[4].

Outlook and Survival

The five-year survival rate of oesophageal squamous cell carcinoma is poor, and there remains globally a pressing need for novel treatments that improve patient outcomes and quality of life^[4].

For esophageal cancer in general in the United Kingdom^[17]:

• Around 45 out of every 100 people survive their cancer for 1 year or more
• More than 15 out of every 100 people survive their cancer for 5 years or more
• Almost 15 out of every 100 people survive their cancer for 10 years or more

Survival depends heavily on the stage at diagnosis. For localized esophageal cancer, the five-year survival rate is about 48%, but it is significantly less when the cancer has spread to other parts of the body^[4].

Unfortunately, only 25% of people with esophageal cancer receive a diagnosis before the cancer spreads^[1]. Approximately half of esophageal cancers are diagnosed at the locally advanced stage, which means there is a significant tumor in the esophagus but the cancer has not yet spread to other parts of the body^[4].

Advanced treatment techniques including radiation therapy, chemotherapy, and immunotherapy have brightened the outlook for survivors^[15]. Medical researchers are working on treatments that will help people with esophageal cancer live longer^[1].

Reducing Your Risk

Esophageal squamous cell carcinoma is largely preventable^[20]. Several actions can reduce the likelihood of getting this cancer.

Stop Smoking and Avoid Tobacco

The best way to lower your risk is to avoid all forms of tobacco, including cigarettes, cigars, pipes, and smokeless tobacco. If you use tobacco, get help to quit. Quitting reduces your risk significantly^[20][21].

Limit Alcohol Consumption

Drinking alcohol increases your risk of developing esophageal squamous cell carcinoma. Drinking alcohol together with smoking tobacco increases the risk more than doing either one alone^[21]. To reduce your cancer risk, it’s best not to drink alcohol. If you choose to drink, have no more than 2 standard drinks a week. The less alcohol you drink, the lower your cancer risk^[21].

Maintain a Healthy Body Weight

Being overweight or obese increases your risk. Eating a diet rich in fruits and vegetables may help you lose weight and can also help reduce your risk of developing esophageal squamous cell carcinoma^[20][21]. Some studies show that cruciferous vegetables, such as cauliflower and cabbage, contain substances that may help prevent esophageal cancer^[20].

Avoid Chewing Betel Quid or Areca Nut

Not chewing betel quid or areca nut lowers your risk of developing esophageal cancer^[21].

Avoid Drinking Very Hot Beverages

Drinking very hot beverages, such as hot coffee, tea, and maté, increases your risk. Let your beverages cool down to lower than 65°C before you drink them^[21].

Limit Red and Processed Meats

Diets high in processed meats may increase the risk of developing squamous cell carcinoma of the esophagus. Avoiding processed meats may help reduce your risk^[21].

Eat More Vegetables and Fruit

Eating a healthy diet that includes lots of vegetables and fruit may lower your risk of developing esophageal cancer^[21].

Be Physically Active

Studies have shown that physical activity may lower the risk of esophageal cancer^[21].

Prevent Human Papillomavirus Infection

Infection with certain types of human papillomavirus can increase your chance of developing squamous cell cancer. The type of HPV that causes esophageal cancer is contracted through oral sex. Practicing safer sex can help reduce your risk^[20].