Types of Treatment for Esophageal Cancer

Executive Summary

Treatment recommendations depend upon the size, grade and type of tumor, metastasis, possible side effects, and patient’s preferences and overall health. The tumor that does metastasize beyond the esophagus and lymph nodes involves treatment of chemotherapy, radiation therapy, and surgery. Sometimes, radiation therapy and chemotherapy are combined in an approach called “chemoradiotherapy.” The order of treatments varies, and various factors are considered, including the type of esophageal cancer. For squamous cell cancer, chemoradiotherapy is commonly suggested as the first treatment. Surgery is recommended afterwards, and chemotherapy is indicated before surgery. Immunotherapy is recommended in those patients who receive chemoradiotherapy and surgery. For adenocarcinoma, the standard treatment is chemoradiotherapy followed by surgery. Surgery is almost always suggested after chemoradiotherapy. For advanced or metastatic esophageal cancer, treatment usually involves radiation therapy, chemotherapy, and other therapies using medication. Palliative care is provided to the patients to cope with mental, physical or financial issues while involving medicine, nutritional changes, emotional and spiritual support and other relaxation therapies. Endoscopy therapy is also suggested as the treatment for esophageal cancer involving endoscopy and dilation, electrocoagulation, endoscopy with stent placement, cryotherapy, and other less-common techniques, including laser therapy and photodynamic therapy. Targeted therapy includes HER2-targeted therapy and anti-angiogenesis therapy.

Treatment for Esophageal Cancer

“Standard to care” refers to the best-known treatment. In cancer care, various doctors work together to bring out an overall treatment plan for the patient. This is called a multidisciplinary team. 

Treatments recommendations depend on many factors:

  • The size, grade and type of tumor
  • If the tumor has increased to other parts of the body
  • Possible side effects
  • The patient’s preferences and overall health 

For a tumor that has not spread beyond the esophagus and lymph nodes, doctors often recommend combining different types of treatment – chemotherapy, radiation therapy, and surgery. Sometimes, radiation therapy and chemotherapy are combined in an approach called “chemoradiotherapy.” The order of treatments varies, and various factors are considered, including the type of esophageal cancer.

For locally advanced esophageal cancer, ASCO recommends a treatment plan that combines different types of treatment.

For squamous cell cancer, chemoradiotherapy is commonly suggested as the first treatment. Surgery can be used afterwards, depending on how well chemoradiotherapy has worked. Recent studies showed that using chemoradiotherapy before surgery is better than surgery alone. ASCO suggests chemoradiotherapy before surgery for all people with locally advanced esophageal squamous cell cancer. This treatment may send cancer into remission in some patients, and surgery may not be needed immediately. Immunotherapy may be recommended in those who receive chemoradiotherapy and surgery if tumor cells are found in the tissue removed during surgery. Few people may not be able to receive radiation therapy. These can receive chemotherapy only before surgery.

For adenocarcinoma, the common treatment is chemoradiotherapy followed by surgery ​1​. Surgery is almost always suggested after chemoradiotherapy, unless factors increase the risks from surgery, such as a patient’s overall health. For locally advanced esophageal adenocarcinoma, ASCO recommends chemoradiotherapy before surgery or chemotherapy before and after surgery. Immunotherapy can be suggested after chemoradiotherapy and surgery if tumor cells are found in the tissue removed during surgery. In that case, chemoradiotherapy alone is the treatment. It’s essential to discuss which treatment options are best for you with your doctor.

For advanced or metastatic esophageal cancer, treatment usually involves radiation therapy, chemotherapy, and other therapies using medication.

Palliative Care 

Cancer and its treatment have side effects that can be mental, physical or financial and managing the effects are palliative or supportive care.

Palliative care includes medication, nutritional changes, emotional and spiritual support and other relaxation therapies. 

Palliative care focuses on alleviating how you feel during treatment by managing symptoms and supporting patients and their families with other non-medical needs. Regardless of type and stage of Cancer age, any person may receive this type of care.

Surgery

Surgery is the removal of the tumor and some nearby healthy tissue in operation. Surgery has traditionally been the common treatment for esophageal cancer ​2​. However, surgery without previous chemotherapy or chemoradiotherapy is the primary treatment only in specific situations.

For most people with locally advanced esophageal cancer, ASCO suggests chemoradiotherapy or chemotherapy before surgery because combined therapy has been shown to help people live longer. Immunotherapy may be recommended after chemoradiotherapy and surgery if tumor cells are still found in the tissue removed during surgery ​3​. The best treatment option is mostly a combination of chemotherapy and radiation therapy if surgery is not possible.

The most common surgery to treat esophageal cancer is called an esophagectomy. The doctor removes the affected part of the esophagus and then connects the remaining healthy part of the esophagus to the stomach to swallow normally. If that is not possible, part of the intestine can sometimes connect. The surgeon also removes lymph nodes around the esophagus.

Surgery for palliative care

In addition to surgery to treat cancer, surgery may help people eat and relieve symptoms caused by cancer. This is known as palliative surgery. To do this, doctors and surgeons called gastroenterologists, who specialize in the gastrointestinal tract ​4​, can –

Put in a feeding tube from which a person can receive nutrition directly into the intestine or stomach. A tube that directly passes nutrition into a person’s stomach is a percutaneous endoscopic gastrostomy (PEG). A feeding tube that directly passes nutrition into a person’s intestine is a percutaneous endoscopic transgastric jejunostomy (PEJ). This can be done before chemotherapy and radiation therapy is given to ensure that the person eats enough food to maintain their weight and strength while the treatment is going on.

Create a bypass, or new pathway, to the stomach if a tumor blocks the esophagus but cannot be removed with surgery. This procedure is used rarely.

People having trouble eating and drinking may require intravenous (IV) feedings and fluids for various days before and after surgery, as well as antibiotics, to prevent and treat infections. Patients are taught special breathing and coughing exercises to keep their lungs clear.

Endoscopic therapy

The following treatments use a flexible, long tube called an endoscope to treat the symptoms associated with esophageal cancer and to manage side effects caused by the tumor.

Endoscopy and dilation – This procedure expands the esophagus. It may have to be repeated if the tumor grows.

Electrocoagulation – This palliative treatment helps destroy cancer cells by heating them using an electric current. Sometimes, this is used to help relieve symptoms by removing a blockage caused by the tumor.

Endoscopy with stent placement – This procedure uses endoscopy to insert a stent into the esophagus. An esophageal stent is a metal mesh device that is expanded to keep the esophagus open.

Cryotherapy – This palliative treatment uses an endoscope attached probe that can freeze and remove tumor tissue. It can reduce the tumor size to help a patient swallow easier.

Other less-common techniques include laser therapy and photodynamic therapy. In photodynamic therapy, a vein gives a light-sensitive substance known as a photosensitizer. Then, a laser is then directed at the esophageal lesions using an endoscope. A laser burns the esophageal lesions through an endoscope in laser surgery.

Radiation Therapy

Radiation therapy uses high-energy X-rays to kill cancer cells. A radiation therapy schedule consists typically of a specific number of treatments offered over a set period.

Radiation therapy can be combined with chemotherapy during treatment.

The most common radiation treatment type is external-beam radiation therapy, given from a machine outside the body.

When radiation treatment is given inside the body directly, it is internal radiation therapy or brachytherapy. This involves inserting a radioactive wire, temporarily, into the esophagus using an endoscope for esophageal cancer.

Proton beam therapy is being studied in clinical trials for esophageal cancer. Proton beam therapy is an external-beam radiation therapy that uses protons rather than x-rays. At high energy, protons can kill cancer cells.

Radiation therapy side effects may include mild skin reactions, fatigue, soreness in the throat, oesophagus, etc. Most side effects go soon after treatment is completed.

Chemotherapy

Chemotherapy uses medicine to kill or stop the growth of cancerous cells. Depending upon the stage, different chemotherapy is given. The point that makes a difference is how the chemotherapy enters the body and which cells it affects.

A chemotherapy schedule usually consists of a certain number of cycles over a fixed period. A patient can be given one drug at a time or a combination of different drugs given simultaneously.

Chemotherapy and radiation therapy are usually given simultaneously to treat esophageal cancer.

The chemotherapy side effects depend on the patient and the dose used. Still, they can include fatigue, risk of infection, nausea and vomiting, hair loss, nerve problems, loss of appetite, and diarrhoea. These side effects usually go after treatment is completed. 

Targeted therapy

Targeted therapy aims at any factor contributing to the growth and development of cancer cells. It can be a specific protein, gene or tissue environment. These treatments are typical and do not harm surrounding cells like those in chemotherapy or Radiotherapy.

Not all tumors have the same cellular traits, so doctors may suggest testing to understand better changes in the individual tumor’s genes and proteins.

This helps doctors better match each patient with the most effective treatment whenever possible. 

Targeted therapy for oesophageal cancer includes

HER2-targeted therapy – For esophageal cancer, the targeted therapy trastuzumab (Herceptin, Ogivri) may be used along with chemotherapy as the first treatment for metastatic esophageal adenocarcinoma. Trastuzumab deruxtecan (Enhertu) is also approved as the first treatment for metastatic esophageal adenocarcinoma. This combines a drug that resembles trastuzumab with strong chemotherapy. For recurrent or metastatic gastroesophageal cancer that is HER2 positive, ASCO, ASCP, and CAP suggest a combination of chemotherapy and HER2-targeted therapy. HER2-targeted therapy is not a treatment option for cancer that is HER2 negative.

Anti-angiogenesis therapy – The targeted therapy ramucirumab (Cyramza) can be a treatment option if first-line therapy has not worked. Ramucirumab is a targeted therapy called anti-angiogenic. It is focused on stopping angiogenesis (making new blood vessels). As a tumor needs the nutrients delivered by blood vessels to grow and spread, anti-angiogenesis therapies aim to ‘starve’ the tumor. Ramucirumab is commonly given with paclitaxel, a type of chemotherapy, but can also be given by itself.

Immunotherapy 

Immunotherapy, a type of biological therapy, uses artificial or natural substances to harness our immune system to fight. It uses substances formed by the body or laboratory to improve, target, or restore immune system function. 

Two types of immunotherapy drugs are approved to treat adenocarcinoma and squamous cell carcinoma of the esophagus and the gastroesophageal junction, which grows in the stomach. Pembrolizumab (Keytruda) and nivolumab (Opdivo) are checkpoint inhibitors that target the PD-1/PD-L1 pathway.

Pembrolizumab (Keytruda) is approved in the following situations-

As a first-line treatment in combination with chemotherapy and trastuzumab for HER2-positive incurable locally advanced or metastatic esophageal and gastroesophageal junction adenocarcinoma and squamous cell carcinoma, regardless of PD-L1 expression.

As a first-line treatment in combination with chemotherapy for incurable locally advanced or metastatic esophageal and gastroesophageal junction adenocarcinoma and squamous cell carcinoma, regardless of PD-L1 expression.

As a second-line treatment for esophageal squamous cell carcinoma that tests CPS positive at 10% or higher, CPS stands for “combined positive score”, and it is a way to measure how many cells express the PD-L1 protein.

It is also approved to treat gastroesophageal junction adenocarcinoma that tests positive for MSI-H or has mismatch repair deficiency after one or more chemotherapy treatments have not stopped cancer.

Nivolumab (Opdivo) is approved –

As a first-line treatment in combination with chemotherapy for oesophageal or gastroesophageal junction adenocarcinoma, regardless of PD-L1 expression.

As a second-line treatment for esophageal squamous cell carcinoma, regardless of PD-L1 expression.

As a post-surgery adjuvant treatment after chemotherapy, radiation, and surgery in esophageal and gastroesophageal adenocarcinoma and squamous cell carcinoma if any cancer cells are present in the tissue removed during surgery. Some research suggests that people with tumors with higher PD-L1 expression may have a greater benefit from adjuvant nivolumab, but this requires more study.

Metastatic oesophageal cancer

When cancer starts spreading to other parts of the body, it is called metastatic cancer. Doctors can have different opinions regarding the best standard treatment plan. Clinical trials might also be an option. For many people, the diagnosis of metastatic cancer is very stressful and challenging. It is usually helpful to talk with other patients through support groups or peer support programs. 

For metastatic esophageal cancer, palliative or supportive care is very important to help relieve symptoms and side effects. The target of treatment is usually to lengthen a person’s life while easing symptoms like pain and problems with eating. Your treatment plan may include chemotherapy and radiation therapy to help relieve pain or discomfort. For example, an esophageal stent, laser therapy, photodynamic therapy, or cryotherapy may help keep the esophagus open.

Remission and the chance of recurrence

When cancer can’t be detected in the body and there are no symptoms, this is known as remission. This may also be called having ‘no evidence of disease’ or ‘NED.’

A remission may be temporary or permanent. Many people worry about the recurrence of cancer.

If treatment doesn’t work

If cancer can’t be treated or controlled, it leads to advanced or terminal cancer. It is vital to have straightforward conversations with your health care team to express your feelings, preferences, and concerns. The health care team has unique skills, knowledge, and experience to assist patients and their families. Ensuring that a person is physically comfortable, free from pain, and emotionally supported is extremely important.

References

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    Ilson DH, van Hillegersberg R. Management of Patients With Adenocarcinoma or Squamous Cancer of the Esophagus. Gastroenterology. Published online January 2018:437-451. doi:10.1053/j.gastro.2017.09.048
  2. 2.
    Pech O, May A, Manner H, et al. Long-term Efficacy and Safety of Endoscopic Resection for Patients With Mucosal Adenocarcinoma of the Esophagus. Gastroenterology. Published online March 2014:652-660.e1. doi:10.1053/j.gastro.2013.11.006
  3. 3.
    Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. The Lancet. Published online May 2002:1727-1733. doi:10.1016/s0140-6736(02)08651-8
  4. 4.
    Shapiro J, van Lanschot JJB, Hulshof MCCM, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. The Lancet Oncology. Published online September 2015:1090-1098. doi:10.1016/s1470-2045(15)00040-6