Esophageal Squamous Cell Carcinoma (ESCC):
ESCC develops in the thin, flat cells lining the inside of the esophagus. This cancer is frequently found in the upper and middle parts of the esophagus, but can occur anywhere along the esophagus. Globally, it is the most common form of esophageal cancer, and, in the East, it continues to be the most prevalent type of esophageal cancer. It represents 90% of all cancers in most Asian, African, and Eastern European countries. Further, it is more common in men than women.
Risk factors associated with ESCC:
In industrialized countries, the two most important risk factors are tobacco use and excessive alcohol consumption, and these two independent risk factors have a synergistic effect on ESCC incidence.
The risk of developing ESCC with active tobacco smoking increases threefold to ninefold. Although the highest risk has been reported with cigarette smoking, other forms of tobacco use such as pipe, cigar, hookah, chewing of tobacco, and the Asian betel nut have also been linked to ESCC. The intensity and duration of tobacco exposure have been reported to be associated with an increased risk of ESCC, as tobacco-specific nitrosamines and polycyclic aromatic hydrocarbons are thought to be the major carcinogenic substances in tobacco.
Alcohol use has been reported to have a slightly lower risk than tobacco. Nevertheless, the risk increases significantly with alcohol intake above the maximum recommended levels of acetaldehyde, the first metabolite of ethanol metabolism, which is a class I (1) carcinogen.
Signs and symptoms of ESCC:
• Painful or difficult swallowing
• Pain behind the breastbone
• Weight loss
• Indigestion and heartburn
• Hoarseness and cough
• Lump under skin
Diagnostic tests for confirming the diagnosis of ESCC:
These tests also aid in determining whether the cancer cells have spread within the esophagus or to other parts of the body. This process is called staging. The information gathered from the staging process determines the stage or extent of the spread of the disease and is important in planning further treatment. The following tests and procedures may be used for diagnosis and staging:
• Endoscopic ultrasound (EUS): A probe at the end of the endoscope is used to bounce high-energy sound waves of internal tissues or organs and create echoes. The echoes form an image of body tissues, which is referred to as a sonogram.
• Biopsy: This involves the removal of cells or tissues to be viewed under a microscope by a pathologist to check for signs of cancer. The biopsy procedure is usually carried out during an endoscopy.
• CT scan (CAT scan): In this procedure, a series of detailed images of areas inside the body, such as the chest, abdomen, and pelvis, are obtained using different angles.
• PET scan (positron emission tomography scan: This procedure is used to find malignant tumor cells in the body. To initiate the procedure, a small amount of radioactive glucose is injected into a vein. Thereafter, the PET scanner scans the entire body and captures images of the parts where glucose is being used. Malignant tumor cells show up brighter in such images because they are more active and absorb more glucose than normal cells
• MRI (magnetic resonance imaging): This procedure involves the use of a magnet, radio waves, and a computer to make a series of detailed images of areas inside the body.
• Thoracoscopy: Through this surgical procedure, organs inside the chest are examined for the purpose of detecting abnormalities.
• Laparoscopy: Through this surgical procedure, organs inside the abdomen are examined to identify signs of disease.
These tests also help in assessing the spread of cancer.
Cancer cells can spread through the following routes:
• Tissue: Cancer spreads from its origins into nearby areas.
• Lymph system: Cancer spreads from the point of origin to other parts of the body through the lymph vessels.
• Blood: Cancer spreads from the point of origin to other parts of the body through the blood vessels. When cancer spreads to another part of the body, it is known as metastasis.
The prognosis and treatment options for ESCC depend on the following:
The stage of the cancer (whether it has affected a part of the esophagus, involves the whole esophagus, or has spread to other body parts), the grade of the cancer, whether the tumor can be completely removed by surgery, and the general health of a patient.
The following stages are used for ESCC:
Stage 0 (high-grade dysplasia) is the earliest stage. The rest of the range involves stages I through IV. As a rule, the lower the number, the lesser is the spread of the cancer. If the number is higher, for example stage IV, it implies greater spread of the cancer. Within a stage, an earlier letter refers to a lower stage.
The following stages are used for ESCC:
Stage 0 (high-grade dysplasia) is the earliest stage. The rest of the range involves stages I through IV. As a rule, the lower the number, the lesser is the spread of the cancer. If the number is higher, for example stage IV, it implies greater spread of the cancer. Within a stage, an earlier letter refers to a lower stage.
The American Joint Committee on Cancer (AJCC) TNM system is the staging system commonly used for esophageal cancer, and it is based on the following three important points:
- extent (size) of the tumor (T),
- spread to nearby lymph nodes (N), and
- spread (metastasis) to distant sites or organs like the lungs or liver (M).
Another factor affecting treatment is the grade of the cancer, which indicates how closely the cancer resembles a normal tissue when viewed under a microscope. Esophageal cancers are graded on a scale of 1 to 3.
When esophageal cancer is detected early, there is a better chance of recovery. However, in most cases, the esophageal cancer is diagnosed at an advanced stage.
Although esophageal cancers in advanced stages can be treated, they can rarely be completely cured.
Stage-wise management of ESCC:
Stage 0 (high-grade dysplasia) is a type of pre-cancer in which abnormal cells look like cancer cells, but are only found in the inner layer of cells lining the esophagus (i.e., the epithelium).
Treatment:
• Surgery
• Endoscopic resection
Stage I
At this stage, the cancer spreads into some of the deeper layers of the esophageal wall (past the innermost layer of cells), but does not reach the lymph nodes or other organs. Depending on the extent of cancer spread, the stage is divided into stages IA and IB.
Treatment:
• Chemoradiation therapy followed by surgery
• Surgery alone
Stage II
Stage II includes cancers that have spread to the main muscle layer of the esophagus or into the connective tissue on the outside of the esophagus. This stage also includes some cancers that have spread to 1 or 2 nearby lymph nodes. This stage is divided into stages IIA and IIB.
Treatment:
• Chemoradiation therapy followed by surgery
• Surgery alone
• Chemotherapy followed by surgery
• Chemoradiation therapy alone
Stage III
Stage III includes some cancers that have spread through the wall of the esophagus and into the outer layer, along with other cancers that have spread to nearby organs or tissues. It also includes most cancers that have spread to nearby lymph nodes. This stage of cancer is divided into stages IIIA and IIIB.
Treatment:
• Chemoradiation therapy followed by surgery.
• Chemotherapy followed by surgery.
• Chemoradiation therapy alone.
Stage IV
A stage IV esophageal cancer spreads to distant lymph nodes or other distant organs. This stage of cancer is divided into stages IVA and IVB.
Treatment:
• Chemoradiation therapy followed by surgery.
• Chemotherapy.
• Immunotherapy with an immune checkpoint inhibitor (nivolumab) as adjuvant therapy.
• Immunotherapy with immune checkpoint inhibitors (nivolumab and ipilimumab).
• Immunotherapy with an immune checkpoint inhibitor (nivolumab) and chemotherapy.
• Laser surgery or electrocoagulation as palliative therapy to relieve symptoms and improve the quality of life.
• An esophageal stent as palliative therapy to relieve symptoms and improve the quality of life.
• External or internal radiation therapy as palliative therapy to relieve symptoms and improve the quality of life.
• Clinical trials with newer chemotherapy agents.
• A clinical trial of targeted therapy combined with chemotherapy.
Targeted Therapies/Immunotherapy:
ESCC patients present at advanced stages and the traditional treatment options are limited to chemotherapy in metastatic settings. With the comprehensive genomic characterization of esophageal cancers, targeted therapy, specifically immunotherapy is gaining interest as these agents can regulate the immune system and improve the survival. Agents such as ramucirumab, trastuzumab, and pembrolizumab are already being used for the treatment of various advanced cancers. Pembrolizumab (a humanized IgG4 monoclonal antibody), in combination with platinum and fluoropyrimidine-based chemotherapy has been approved for use in patients with metastatic or locally advanced esophageal or gastroesophageal junction cancers who are not candidates for surgical resection or definitive chemoradiation, for more than a year. With recent regulatory approvals, therapeutic options for patients with advanced or metastatic ESCC now also include nivolumab (a fully human IgG4 monoclonal antibody) either in combination with fluoropyrimidine- and platinum-based chemotherapy or in combination with ipilimumab (a fully human IgG1κ monoclonal antibody).
Our Services:
Bioviser Medical Writing team is working with a large pharmaceutical company and providing services for writing, editing, fact checking and publication support towards publication of a subgroup analysis of a large clinical trial of targeted therapy in advanced esophageal squamous cell carcinoma.
ESCC is among the most severe forms of malignancy in humans characterized by late-stage diagnosis, metastasis, therapy resistance, and frequent recurrence. Immunotherapy regimens are thus expected to expand treatment options.
Clinical management of ESCC remains challenging and the disease presently lacks significant
and approved targeted therapeutics. However, emerging data from recent clinical trials hold great promise for future progress towards improving patient outcomes in the case of ESCC.
