Early Symptoms, Risk Factors and Treatment Options for Esophageal Cancer

An expert discusses early symptoms, risk factors and treatment options for patients with esophageal cancer.

In a recent Q&A with CURE, Dr. Nataliya Uboha discussed how difficulty swallowing is often an early sign of esophageal cancer, though it can be confused with common digestive issues. Patients are typically treated for heartburn before more serious symptoms, like weight loss, lead to a diagnosis. Uboha highlighted the importance of early detection and noted that different types of esophageal cancer have varying risk factors.

Treatment options depend on the stage of the cancer, with early cases often being treated with surgery and chemotherapy. In more advanced stages, other therapies like immunotherapy or targeted treatments may be considered. Uboha also mentioned the ongoing research aimed at expanding treatment options and improving patient outcomes.

Uboha is a medical oncologist at UW Health, as well as an associate professor and researcher in the Department of Medicine at the University of Wisconsin School of Medicine and Public Health

We sat down with Uboha to discuss the early symptoms of esophageal cancer, risk factors, treatment options and ongoing advancements in research.

CURE: What are some of the early symptoms of esophageal cancer, and how can patients distinguish them from common digestive issues like acid reflux or GERD?

Uboha: One of the most common presenting symptoms of patients with esophageal cancer is dysphagia, which is difficulty swallowing. It is not infrequent that patients come to see their primary care providers with non-specific symptoms such as heartburn and are initially treated with anti-acid medications.

Ultimately, these symptoms progress, do not respond to treatments and patients come in with weight loss and inability to swallow especially solid food, which ultimately result in workup with endoscopy. And that's how the diagnosis is frequently made.

What are some of the major risk factors for developing esophageal cancer, and are there any lifestyle changes that can help lower a person's risk?

There are two different types of esophageal cancers that are seen, squamous cell cancer and adenocarcinoma. Worldwide, squamous cell cancers are much more common. They're not that common in the United States. Squamous cell cancers are related to smoking, and so certainly decreasing smoking or smoking cessation could result in decrease in seeing this cancer in patients.

But adenocarcinoma, which is what we most frequently see in the United States, and which is on the rise, is thought to be related to obesity, heartburn, Barrett's esophagus is a known risk factor, but in many patients, we cannot clearly identify the risk factor that put them at risk for developing this disease.

What treatment options are available for esophageal cancer, and how do you determine the best course of action for each patient?

The stage of disease is very important. So whenever anybody is diagnosed with cancer, we need to find out what stage their disease is, because that can certainly dictate what treatments we should offer and what we can accomplish with treatments. In early-stage cancer, surgery plays a critical role. We can cure patients with early-stage esophageal cancer, but surgery alone is not sufficient, and now we give perioperative chemotherapy for patients with esophageal cancer, and even chemotherapy before and after resection.

And the role behind this chemotherapy is to reduce the risk of cancer coming back or reduce the risk of recurrences. In advanced disease we are becoming much more nuanced with our treatments, and biomarker testing is critical for picking the right treatments. We use treatments like chemotherapy, immunotherapy and targeted agents such as anti-clot and anti HER2 drugs.

How do treatments such as surgery, chemotherapy, radiation, affect the patient's ability to eat and swallow and what supportive care options are available for patients?

Chemotherapy can, in many patients, work quite quickly in improving patients’ ability to swallow. So whenever patients are seeing responses or whatever patient’s tumors respond to treatment, patients can quickly notice that they're able to eat solid foods much easier. I tell my patients that oftentimes they will know before me whether the treatment is working for them. Because we get scans after an average of four to six treatments, but patients who respond to treatment are able to notice improvements in their swallowing with just a couple of treatments of chemotherapy and immunotherapy.

That being said, having multidisciplinary care that involves a registered dietitian, and nutritionist is very important because we sometimes have to support our patients even with tube feeds to get through treatments. Some patients who do not respond quickly enough to treatments with chemotherapy and immunotherapy can benefit from radiation to their tumors as well. So there's many different modalities we can utilize to help patients swallow easier and to make sure that their nutritional status is maintained.

What role do newer treatment approaches like immunotherapy or targeted therapy play in improving outcomes for patients?

Immunotherapy is now approved in the treatment of patients with advanced disease. We add immunotherapy to chemotherapy, and with the addition of immunotherapy, we're seeing more patients’ tumor shrinking or responding to treatments. And what we are seeing, and we very excited about, is that patients who respond tend to respond for longer periods of time.

So we are now seeing some patients who are able to survive with metastatic disease, even two to three years and longer. And so that's really encouraging to see. In early stage, thus far, we've only been using immunotherapy in this rare subset of patients with microsatellite unstable disease, or patients who have tumors that have many, many different mutations and who are specifically sensitive to immunotherapy.

And what we are hoping is that maybe with time, you'll be able to even avoid surgery in some patients with this disease. But this is still under investigation. We have recently heard that one of the big global clinical trials that added immunotherapy to chemotherapy in patients with early-stage disease has also had positive results. So it is possible that we'll be using immunotherapy even in early stage gastric and GE junction esophageal cancer, but those results have not been fully presented yet. The name of this study is MATTERHORN.

Are there any other additional clinical trials or advancements in research that are offering hope for patients right now?

Yes, there are several other drugs that are entering clinic or have entered clinic already. We are now using anti-clotting antibodies. These drugs bind to clotting on the surface of gastroesophageal junction and gastric cancer cells. And Vyloy (zolbetuximab) is an anti-clotting antibody that is now approved for the treatment of GE junction and gastric cancer in combination with chemotherapy.

And there are many other agents that are being developed that target the same biomarker on the cancer cells. In gastroesophageal junction tumors we are also looking forward to getting the results from FORTITUDE trial that look that looked at the activity of anti FGFR2b antibody, bemarituzumab, in the management of this disease. And then there's other immunotherapy drugs that are being developed in advanced disease.

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