In 2024, the NIH’s National Cancer Institute reported approximately 22,370 new esophageal cancer cases and 16,130 deaths from the disease in the United States. Esophageal cancer is a disease in which malignant cells, or cancer cells, form in the tissues of the esophagus.

The esophagus is the hollow, muscular tube that moves food and liquid from the throat to the stomach. The wall of the esophagus is made up of several layers of tissue, including mucous membrane, muscle and connective tissue. Esophageal cancer starts on the inside lining of the esophagus and spreads outward through the other layers as it grows.

The two most common forms of esophageal cancer are named for the type of cells that become malignant:

• Squamous cell carcinoma refers to cancer that forms in the thin, flat cells lining the inside of the esophagus. This cancer is most often found in the upper and middle part of the esophagus but can occur anywhere along the esophagus.
• Adenocarcinoma refers to cancer that begins in glandular cells. Glandular cells in the lining of the esophagus produce and release fluids such as mucus. Adenocarcinomas usually form in the lower part of the esophagus, near the stomach.

Despite a slight decline in esophageal cancer incidence and mortality in recent years, the disease continues to affect populations differently. Men are approximately four times more likely than women to be diagnosed with this cancer. Risk increases with age across all racial and ethnic populations. Among men, White individuals have higher rates of both diagnosis and mortality compared to Black individuals. Among women, Black women are more likely to develop the disease up to age 74, after which White women have a higher risk. Similarly, Black women experience higher mortality rates until age 69, with rates becoming higher among White women thereafter.

Avoiding cancer risk factors may help prevent certain cancers, including esophageal cancer. Anything that increases your risk of getting a disease is called a risk factor. However, having a risk factor does not mean that you will get cancer. Similarly, not having risk factors doesn't mean that you will not get cancer.

Risk factors that can increase the risk of esophageal cancer are:

• Tobacco use.
• Heavy alcohol use.
• Gastric reflux, or gastroesophageal reflux disease (GERD).
• Barrett esophagus—a condition, caused by GERD, in which the cells lining the lower part of the esophagus have changed or been replaced with abnormal cells.
• Older age.
  

Signs and symptoms of esophageal cancer include:

The prevalence of esophageal cancer is slowly increasing, especially related to metabolic syndrome,” said Davendra Sohal, MD, MPH, FASCO, Associate Director of Clinical Research at the Cancer Center. “Unfortunately, initial symptoms are vague—such as heartburn, reflux and difficulty swallowing. It is important to get evaluated as soon as possible when symptoms like this persist.”

Davendra Sohal, MD, MPH, FASCO Associate Director of Clinical Research University of Cincinnati Cancer Center Professor, Department of Internal Medicine University of Cincinnati College of Medicine

“Yes, and if diagnosed, please seek care, ideally at a high-volume center with a multidisciplinary tumor board team as these kinds of centers are associated with improved outcomes due to coordinated, expert-driven care,” added Olugbenga Olowokure, MD, a researcher at the Cancer Center. “Obtaining a second opinion is acceptable, and often valuable, but it should be done quickly as to avoid unnecessary delays in treatment initiation.”

Olugbenga Olowokure, MD Associate Member, Experimental Therapeutics Research Program University of Cincinnati Cancer Center Professor, Department of Internal Medicine University of Cincinnati College of Medicine

Different types of treatment are available for patients with esophageal cancer. These include standard treatments currently in use, as well as newer approaches being tested through clinical trials. A treatment-based clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.

The following treatments can be used:

• Surgery.
• Radiation therapy.
• Chemotherapy.
• Chemoradiation therapy.
• Laser therapy.
• Electrocoagulation.
• Immunotherapy.

Over the last five years, the role clinical trials play in advancing our knowledge for better patient outcomes cannot be over emphasized,” said Olowokure. “We have learnt to in cooperate immunotherapy and chemotherapy combinations in the treatment of esophageal cancer patients for better patient outcomes. There have been approvals for various immunotherapy agents like nivolumab, pembrolizumab and tislelizumab in combination with chemotherapy for the management of appropriate patients.”

Immunotherapy is a treatment that uses the patient’s immune system to fight cancer. This treatment approach utilizes substances produced by the body or created in a laboratory to boost, direct or restore the body’s natural defenses against cancer.

“A lot of improvement has been made—from endoscopic methods to detect and treat very early-stage esophageal cancers to immunotherapy drugs for advanced metastatic cancer,” Sohal added. “However, we need more progress. The disease remains difficult to treat overall. We are working on clinical trials that use novel immunotherapy drugs to treat this cancer.”

One such clinical trial focused on improving current treatments is the Phase 2 Study of Sotigalimab, a CD40 Agonist Antibody, plus Concurrent Chemoradiation as Neoadjuvant Therapy for Esophageal and Gastroesophageal Junction Cancers trial that Sohal has worked on.

Neoadjuvant chemoradiation (NCRT) followed by surgical resection represents a standard approach for patients with locally advanced esophageal or gastroesophageal junction (GEJ) cancers. Sotigalimab—a high-affinity CD40 agonist antibody—can induce and expand antitumor immune responses by activating dendritic cells, T and B lymphocytes, NK cells and M1 macrophages. This study examined the safety and efficacy of combining sotigalimab with NCRT in patients with esophageal or gastroesophageal junction cancers.

“This trial studied a novel immunotherapy approach for patients with localized esophageal cancer, as opposed to advanced cancer,” said Sohal. “It was an important trial and showed promising results from two perspectives—testing a new immunotherapy approach and testing it in early-stage esophageal cancer.”

In this study, 33 patients with esophageal or gastroesophageal junction (GEJ) cancer received a combination of standard chemoradiation and sotigalimab—the immune-activating drug. Most patients (90%) received all planned doses of sotigalimab with common side effects of nausea, fatigue and mild immune reactions. Among the 29 patients who could be evaluated, 25—or 88%—had complete tumor removal, and 11—or 38%—showed no remaining cancer in tissue samples after treatment. Furthermore, an analysis of post-treatment samples revealed increased activity of immune cells involved in fighting cancer.

“The addition of sotigalimab to the standard chemoradiation was generally safe and showed promising results, including a high rate of complete tumor response,” Sohal shared. “These findings suggest that this could be a valuable treatment approach and support further research into using immune-based therapies before surgery for esophageal and GEJ cancers. The next step is to plan a larger study in this population that can definitively answer the question.”

Sohal is passionate about expanding access to cutting-edge clinical research for patients. Through his leadership, the Cancer Center continues to grow its portfolio of innovative trials, giving more patients access to promising new therapies and the hope of improved outcomes.

“Witnessing patients, who originally had no options left, improve via clinical trial treatment has been a real defining moment in my work,” Sohal said. “I am most proud of the expansion of our clinical trials portfolio here at the Cancer Center. Clinical trials are the only way to find better treatments for cancer, and at times, they are the only path for patients.”

Similarly, Olowokure is driven by a deep commitment to patient care and the belief that every interaction is an opportunity to make a meaningful impact.

“Agreed, trying to make a positive difference in a patient’s life is what excites me the most about my work,” Olowokure expressed. “At the Cancer Center, we are truly unified and committed to delivering compassionate care. We all have one goal—to see our patients thrive.”