Research in esophageal cancer

We are always learning more about cancer. Researchers and healthcare professionals use what they learn from research studies to develop better ways to treat esophageal cancer. The following is a selection of research showing promise for treating esophageal cancer.

We've included information from the following sources. Each item has an identity number that links to a brief overview (sometimes called an abstract).

• PubMed, US National Library of Medicine (PMID)
• American Society of Clinical Oncology (ASCO)
• ClinicalTrials.gov (NCT)

Researchers are looking for better ways to treat esophageal cancer using surgery and improve how surgery is done.

Removing lymph nodes is a standard part of an esophagectomy to remove the esophagus. The number of lymph nodes that have cancer are part of staging esophageal cancer, but it is not known if removing more lymph nodes improves survival or reduces the risk of the cancer coming back after surgery. Researchers compared 2 groups of people who had surgery to remove their esophagus. One group had lymph nodes removed from 3 areas (the neck, chest and abdomen) and the other group had lymph nodes removed from 2 areas (the chest and abdomen). The study, which focused on people who had tumours in the middle to lower part of the esophagus, showed similar disease-free survival and overall survival in the 2 groups. These results suggest that surgery to remove more lymph nodes than are needed for staging may not be necessary (Journal of Thoracic Oncology, PMID 33307192).

Delaying surgery after chemoradiation until it is needed may help delay the significant side effects of surgery and improve quality of life. A clinical trial will compare a group of people having the standard treatment of neoadjuvant chemoradiation followed by surgery with another group of people who will have surgery only if cancer comes back after chemoradiation (ClinicalTrials.gov, NCT 04460352).

Robot-assisted surgery to remove the esophagus was shown in a clinical trial to improve outcomes after surgery. During this type of surgery, the surgeon sits near the operating table and controls robotic arms that perform the operation through several small cuts (incisions) in the chest. Compared to people who had standard minimally invasive surgery, people who had a robot-assisted surgery had fewer surgical complications, including anastomotic leaks, and shorter hospital stays (Frontiers in Oncology, PMID 36059666; Surgical Endoscopy, PMID 36097100). Robot-assisted surgery requires special equipment and extensive training that is very expensive, so it may not be available at all hospitals even if it does become an accepted treatment for esophageal cancer.

Researchers are looking for better ways of using radiation therapy to treat esophageal cancer.

Intensity-modulated radiation therapy (IMRT) is a specialized form of radiation therapy. IMRT gives external beam radiation in a targeted way using computers to vary the shape of the radiation field and the intensity of the dose delivered. This technique maximizes radiation to the tumour and minimizes the amount of radiation that normal tissue is exposed to.

• A study compared boosting the amount of radiation delivered by IMRT, either at the time of chemoradiation or at a later time. Results showed that the main difference between the 2 groups was that there was better local control of the cancer in the group that were given the radiation boost at the same time as chemoradiation, but there was no difference in the overall survival rate (Frontiers in Surgery, PMID 35677748).
• Higher doses of radiation given by IMRT during chemoradiation showed a better survival in people who had locally advanced esophageal cancer that couldn't be removed with surgery when compared to people who had a lower dose of radiation as a treatment (Medicine (Baltimore), PMID 35482986).

Proton beam radiation therapy uses proton beams instead of x-ray beams to destroy cancerous tissue. X-ray beams release energy before and after they hit their target. Proton beams are different because they release most of their energy after travelling a certain distance. As a result, proton beams cause very little damage to tissues that they pass through and more radiation can be delivered to the tumour. Researchers are studying chemoradiation with proton beam radiation therapy in people with esophageal cancer (Journal of Gastrointestinal Oncology, PMID 32175118; ClinicalTrials.gov, NCT 03801876, NCT 05055648). However, not all studies have shown that there is an advantage using proton beams (Cancers (Basel), PMID 35454939; PMID 36011037). The machines needed to make protons are expensive and this type of radiation therapy may not be available at all treatment centres.

Chemoradiation is often used to treat esophageal cancer. Chemotherapy may also be used on its own. The following research shows promise in treating esophageal cancer:

Carboplatin and paclitaxel are being combined with external radiation therapy in a clinical trial. The goal of the trial is to find out if adding these chemotherapy drugs to radiation therapy improves swallowing problems in people who have esophageal cancer that can't be removed by surgery (ClinicalTrials.gov, NCT 02297217).

Oxaliplatin and capecitabine (Xeloda) were compared to cisplatin and paclitaxel in people who had adenocarcinoma of the gastroesophageal junction. Each chemotherapy combination was given along with external radiation therapy before surgery. Results of the study showed that there was better overall survival and progression-free survival with the combination of cisplatin and paclitaxel (European Journal of Cancer, PMID 33307192).

Chemotherapy given after neoadjuvant chemoradiation and surgery may help improve the survival of people with squamous cell esophageal cancer who had cancer left behind after surgery (Journal of Personalized Medicine, PMID 36013201).

Targeted therapy uses drugs to target specific molecules (such as proteins) on cancer cells or inside them. These molecules help send signals that tell cells to grow or divide. By targeting these molecules, the drugs stop the growth and spread of cancer cells and limit harm to normal cells. The following targeted therapy drugs are showing promise in treating esophageal cancer.

Regorafenib (Stivarga) is being studied in a phase 3 clinical trial as a treatment for people who have adenocarcinoma of the gastroesophageal (GE) junction. The clinical trial, called INTEGRATE lla, is comparing regorafenib to a placebo as a treatment for locally recurrent or metastatic tumours that have not responded to 2 or more types of chemotherapy (ClinicalTrials.gov, NCT 02773524).

Bevacizumab (Avastin) is a targeted therapy drug that shrinks blood vessels. The combination of bevacizumab, gemcitabine and cisplatin was compared to gemcitabine and cisplatin as the first treatment given to people diagnosed with esophageal cancer. The results showed that people treated with bevacizumab, gemcitabine and cisplatin had a higher survival rate after 2 years compared to people who were treated with just gemcitabine and cisplatin (Biomedical Research International, PMID 35480138).

Zanidatamab is a new monoclonal antibody that targets adenocarcinoma tumours of the gastroesophageal junction that are HER2 positive. A new study called HERIZON-GEA-01 is comparing zanidatamab and chemotherapy, with or without tislelizumab (an immunotherapy drug), to trastuzumab and chemotherapy, as the first treatment in people with advanced or metastatic adenocarcinoma tumours. The study will look at how effective and safe the new treatment is (Future Oncology, PMID 36000541; ClinicalTrials.gov, NCT 05152147).

Immunotherapy helps to strengthen or restore the immune system's ability to find and destroy cancer cells. The immune system normally stops itself from attacking normal cells in the body by using specific proteins called checkpoints, which are made by some immune system cells. PD-1 is an immune checkpoint protein that stops T cells from attacking other cells in the body. It does this by attaching to PD-L1, a protein found on some normal cells and some cancer cells. Checkpoint inhibitor drugs may target either PD-1 or PD-L1 proteins.

Combining immunotherapy drugs with chemotherapy drugs is called chemoimmunotherapy. Research is looking at the following chemoimmunotherapy with PD-1 checkpoint inhibitors as potential treatments for esophageal cancer:

• sintilimab (BMJ, PMID 35440464; Nature Communications, PMID 35165274)
• tislelizumab (Cancer Control, PMID 35926155)
• camrelizumab (Frontiers in Immunology, PMID 35911723; Cancer Management and Research, PMID 35795828; International Journal of Cancer, PMID 35188268)
• toripalimab (Journal of Gastrointestinal Oncology, PMID 35557591; Oncologist, PMID 35305102)

The following are other noteworthy developments in esophageal cancer research.

Prehabilitation uses exercise, nutrition and psychological support to improve a person's overall physical and mental health before having treatment. The goal is to help people cope better with the significant side effects of surgery to remove all or part of the esophagus and the side effects of chemoradiation treatment for esophageal cancer. Prehabilitation studies show that it can improve nutritional status, physical fitness and quality of life. Some studies also suggested that prehabilitation can also help reduce the chance of dying because of surgery (Cancers (Basel), PMID 35565226; Diseases of the Esophagus, PMID 35795994, PMID 34875680; British Journal of Sports Medicine, PMID 35105604).

The Thoracic POISE project is looking at dietary supplements, nutritional counselling, physical activity recommendations and psychological support as part of an integrative healthcare approach to care for people with esophageal cancer. The intent of the study is to see if adding integrative healthcare practices can improve quality of life, reduce surgery side effects and help improve survival (ClinicalTrials.gov, NCT 04871412).

Researchers continue to try to find out more about cancer. Clinical trials are research studies that test new ways to treat cancer. They also look at ways to prevent, find and manage cancer.

Clinical trials provide information about the safety and effectiveness of new approaches to see if they should become widely available. Most of the standard treatments for esophageal cancer were first shown to be effective through clinical trials.

Find out more about clinical trials.