Esophageal Cancer: Causes, Diagnosis, Staging, and Treatments

The esophagus is like a highway connecting the bustling city of your mouth to the essential hub of your stomach. Just as a smooth, unobstructed roadway allows for an easy flow of traffic, a healthy esophagus allows the smooth journey of food and liquids from the mouth to the stomach. If parts of this roadway start to wear down, the flow of traffic is hindered, causing delays. 

This is similar to what happens in esophageal cancer, where abnormal cells begin to grow in the mucosal lining of the esophagus, hindering and obstructing the normal passage of food to the stomach. 

Esophageal cancer is the sixth leading cause of cancer death worldwide, resulting in approximately half of a million deaths in 2020. The overall 5-year survival rates for esophageal cancer are relatively low, ranging from 15% to 25%. 

This article explores the risk factors, diagnosis, staging, and treatment options for esophageal cancer to help healthcare providers and patients better navigate this diagnosis.

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Understanding Esophageal Cancer

Esophageal cancer is a severe and potentially fatal disease. The esophagus is the hollow, muscular tube that moves food from the mouth to the stomach. It is classified into three parts, the upper, middle, and distal (lower) esophagus. 

Esophageal cancer forms in the tissue lining the esophagus. Understanding its types, risk factors, symptoms, early detection, and treatment can help with treatment and management.  

The two primary types of esophageal cancer are squamous cell and adenocarcinoma:  

• Squamous cell carcinoma originates from the squamous cell lining of the esophagus. It commonly occurs in the upper and middle esophagus and is associated with smoking and alcohol consumption.  
• Adenocarcinoma originates in the glandular cells of the esophagus and is usually found in the distal part of the esophagus, where the esophagus merges with the stomach. This type is linked to a precancerous condition called Barrett’s esophagus, which is caused by chronic acid reflux.  

The incidence of esophageal cancer tends to rise with age, with the majority of diagnoses occurring after the fifth decade of life. It affects more men than women, exhibiting a male-to-female ratio of about 2-4:1. 

Geographically, esophageal cancer is notably more prevalent in Asia, particularly from China through central Asia to Iran, an area referred to as the ”esophageal cancer belt.” In contrast, it is less prevalent in Western Europe, North America, and Africa. 

While squamous cell is the predominant type globally, there has been a significant increase in the incidence of esophageal adenocarcinoma in Western countries in recent years.  

Causes and Risk Factors

Multiple factors influence esophageal cancer, and understanding these can help in its prevention and early detection. Squamous cell carcinoma is commonly associated with smoking and excessive alcohol consumption. 

Adenocarcinoma, on the other hand, is often linked to chronic gastroesophageal reflux disease (GERD). Over time, chronic GERD can progress to Barrett’s esophagus, a precancerous condition characterized by the transformation of cells lining the distal esophagus into cancerous cells.

In addition to alcohol, tobacco, and GERD, additional risk factors for esophageal cancer include: 

• Diets high in processed meats and low in vegetables and fruits have been associated with increased risk. 
• Obesity is commonly associated with increased GERD. Additionally, obesity can cause inflammation in the esophagus that may cause cells to become cancerous.
• Occupational exposures to certain solvents and carcinogens such as asbestos.

Symptoms of Esophageal Cancer 

Esophageal cancer is often asymptomatic in its early stages. However, as the disease progresses, symptoms typically emerge, prompting individuals to seek medical attention and undergo diagnostic evaluations. Common symptoms of esophageal cancer include: 

• Dysphagia -  Dysphagia refers to difficulty swallowing. It often begins with difficulty swallowing solid foods, particularly meat. As the tumor increases in size and the esophagus narrows, it may progress to the point where even liquids are hard to swallow.  People often describe dysphagia as a sensation of food getting “stuck in their chest or throat”.   
• Unintentional weight loss - This is often due to dysphagia and resulting decreased food intake.  

Less common symptoms include chest pain, heartburn that does not go away with treatment, chronic cough, hoarseness, and/or vomiting or coughing up blood. Not everyone with esophageal cancer will experience these symptoms. 

Additionally, symptoms can vary depending on the location and extent of the tumor. For example, a tumor in the upper esophagus may cause dysphagia in earlier stages of the disease, while a distal tumor may present with heartburn or chest pain.

Diagnosis of Esophageal Cancer

Early diagnosis of esophageal cancer and prompt intervention are essential to improving treatment outcomes, quality of life, and survival. The diagnosis of esophageal cancer involves a series of tests to confirm the presence of cancerous cells and to assess the extent of the disease for staging. Below are the most commonly performed tests in the order that they are typically performed:  

• Endoscopy - Typically, the first step in evaluation is an endoscopy, which consists of inserting a thin, flexible tube equipped with a camera (endoscope) into the esophagus. This allows clinicians to view the lining of the esophagus and check for any growths or abnormalities.
• Endoscopic Ultrasound (EUS) - During an endoscopy, an ultrasound probe with a needle for performing a biopsy will be inserted into the esophagus (EUS). EUS is used to evaluate the depth of the tumor and also obtain tissue for biopsy; it also allows biopsy of nearby lymph nodes. An EUS is one of the most accurate tests used to diagnose esophageal cancer.
• Barium Swallow - This test assesses the esophagus for any obstructions or abnormalities. During the test, the patient drinks a thick, barium-containing liquid that coats the lining of the esophagus. A radiologist then evaluates the x-ray for any abnormalities.
• Computed Tomography (CT) Scan - A chest CT scan provides cross-sectional images of the thorax, including the esophagus. It can help determine the tumor size and its spread into lymph nodes and nearby organs.  
• Positron emission tomography (PET) scan - A PET scan can be used to determine the metabolic activity of a tumor. This is done by injecting a radioactive sugar (FDG) into a person’s blood and monitoring its uptake by cells. The uptake is quantified as the standard uptake value (SUV). Cancer cells absorb more glucose than normal cells, and a higher SUV indicates a more metabolically active and aggressive tumor. A PET scan is also used to look for cancer spread beyond the esophagus (metastasis).  

Staging Esophageal Cancer

Accurate staging for esophageal cancer is paramount for determining the extent of the disease and treatment planning. 

The most commonly used system for classification of esophageal cancer is the TNM system:  

• T (Tumor) - The T stage refers to the size and depth of the tumor. It ranges from T0 (no tumor), T1 (tumor invades the upper layers of the lining of the esophagus) to T4 (tumor extends adjacent structures).  
• N (Nodes) - The N stage reflects cancer spread to the lymph nodes. It ranges from N0 (no spread to the lymph nodes) to N3 (spread of tumor to seven or more lymph nodes).
• M (Metastasis): M0 means no distant spread of disease (metastasis), while M1 indicates the spread of esophageal cancer to other organs and structures.

Once the TNM staging has been performed, the esophageal cancer is then grouped into stages I through IV:

• Stage I indicates that the tumor is confined to the esophagus and has not spread to lymph nodes or distant organs.  
• Stage II: Cancer has spread to nearby lymph nodes or extends deeply into the esophageal wall.  
• Stage III: The tumor that has spread deeply into the esophagus, nearby tissues, or to more lymph nodes. 
• Stage IV indicates the tumor has spread to distant parts of the body (metastasis).

Treatment Options for Esophageal Cancer

A variety of therapeutic strategies are used to treat esophageal cancer, depending on the cancer stage and location, as well as the patient’s overall health. 

Treatment effectiveness is enhanced when a multidisciplinary team works collaboratively. The team typically consists of an oncologist, radiologist, radiation oncologist, surgeon, dietician, and other health care providers. Common treatments are described below.

• Surgery: For patients with early-stage cancer, an esophagectomy is often considered the best treatment option. An esophagectomy involves the surgical removal of all or part of the esophagus, with a goal of complete tumor removal (R0 tumor resection).  
• Radiation Therapy: Radiation therapy uses high-energy rays to kill tumor cells. It can be used alone or in combination with chemotherapy (chemoradiotherapy). The primary goals of radiation therapy are to shrink the tumor, alleviate symptoms, and control the spread of cancer. 
• Chemotherapy: For advanced-stage tumors, chemotherapy may be given before (neoadjuvant) or after (adjuvant) surgery. The goal of neoadjuvant chemotherapy is to shrink the tumor, making it easier to resect and improving the survival rate. In contrast, the goal of adjuvant chemotherapy is to kill the remaining cancer cells after surgery and to reduce the risk of recurrence.  
• Targeted Therapy and Immunotherapy: Target therapy drugs specifically attack cancer cells without harming normal cells. They are used based on the presence of specific genetic markers in the tumor cells (e.g., EGFR). Immunotherapy is another treatment option. Immunotherapy treatment helps the immune system recognize and attack cancer cells. For example, pembrolizumab and nivolumab target a protein (PD-1) on T cells (a type of immune system cell). The PD-1 protein normally helps keep T cells from attacking other cells in the body and subsequently boosts the immune system’s ability to attack cancer cells. Immunotherapy is generally used for advanced-stage cancers or for cancer that is non-responsive to other therapies.  
• Palliative Care: Palliative care plays a crucial role in managing symptoms and improving the quality of life for people with advanced-stage esophageal cancer. It often consists of pain management, palliative procedures (e.g., radiation therapy, esophageal stenting), dietary support, and counseling to address the psychological impact of the disease.  

Living with Esophageal Cancer

Esophageal cancer and treatments can pose significant challenges for patients physically and emotionally. Managing nutritional needs and addressing emotional well-being are key aspects of comprehensive care.   

• Nutritional Support: Nutritional support is often needed in those with esophageal cancer, primarily due to dysphagia resulting from the tumor and side effects from chemotherapy.  Dietary modifications may be necessary to switch to soft foods or liquids that are easy to swallow. A consultation with a dietician can provide a tailored diet plan aimed at specific needs, such as managing nausea or vomiting. In cases where swallowing is not possible, a feeding tube may be needed to provide adequate nutrition and hydration.    
• Emotional and Psychological Support: The diagnosis of esophageal cancer can be overwhelming, potentially leading to anxiety and depression. Managing the psychological aspect and providing emotional support is essential. Oncology social workers, counselors, and psychologists can provide support and therapy to help patients and their families cope with the emotional challenges of cancer. Support groups can also provide a sense of community and mutual support.  

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Key Takeaways

• The two primary types of esophageal cancer are squamous cell and adenocarcinoma.  Each of these is characterized by different risk factors and locations within the esophagus.  
• The primary risk factors for esophageal cancer include tobacco use, alcohol consumption, chronic GERD, and obesity. 
• Diagnosis of esophageal cancer includes endoscopy and biopsy to confirm the presence of cancer. Commonly used imaging tests include barium swallow and CT and PET scans to assess the tumor size, spread, and lymph node involvement.  
• The staging of esophageal cancer is essential for treatment planning. It utilizes the TNM system to classify the tumor size (T), lymph node involvement (N), and metastasis (M). Staging ranges from I (localized disease) to IV (metastasized) and is crucial for determining the best treatment approach.  
• Treatment options for esophageal cancer include surgery, radiation therapy, chemotherapy, targeted therapy, and immunotherapy. The choice of treatment depends on the stage of cancer, with a combination of therapies often employed for advanced-stage tumors.  
• Working collaboratively with healthcare providers, staying informed about the latest treatment options, emotional support, and maintaining hope are pivotal in navigating the complexities of esophageal cancer.