Awareness Efforts Aim to Drive Earlier Esophageal Cancer Detection Amid Rising Incidence Rates

Nataliya Uboha, MD, PhD

In the absence of active screening programs, esophageal cancer educational initiatives may facilitate earlier detection of this increasingly prevalent malignancyby encouraging timely symptom recognition and heightened vigilance among patients and oncologists, according to Nataliya Uboha, MD, PhD, who added that these factors could lead to more diagnoses at potentially curable stages.

“Esophageal cancer is not a very common cancer, but [its incidence] is on the rise,” Uboha said in an interview with OncLive® highlighting Esophageal Cancer Awareness Month, which is observed each April. “Unfortunately, patients [with esophageal cancer often] present with symptoms that can mimic common diseases, such as heartburn. They are treated for heartburn, so the diagnosis is delayed. Then, when patients are ultimately diagnosed with this cancer, it is in advanced stages and is incurable.”

During the interview, Uboha discussed the current incidence of esophageal cancer subtypes globally and in the United States (US); detailed the shift in treatment approaches for esophageal adenocarcinoma to include perioperative chemotherapy; and emphasized the need to balance treatment-related toxicities with improvements in patient quality of life [QOL].

Uboha is a faculty leader for the Early Phase Oncology Therapeutics Program at the University of Wisconsin Carbone Cancer Center, as well as an associate professor and researcher in the Department of Medicine at the University of Wisconsin School of Medicine and Public Health in Madison.

OncLive: What is the role of endoscopy in esophageal cancer diagnosis and management? Are there any areas where a lack of access to screening results in more late-stage diagnoses?

Uboha: It’s important for patients, as well as physicians, to think about [esophageal cancer] diagnosis when patients are seen in clinic, because detection is important. If we can detect this cancer at early stages, we can cure patients.

Endoscopy remains the main diagnostic procedure when patients undergo workup for this cancer. A lot of times, patients present with nonspecific symptoms, such as heartburn. Ultimately, these symptoms may progress to a sensation of food getting stuck—or dysphagia, and pain with swallowing—or odynophagia. The diagnosis [of esophageal cancer] is typically made with endoscopy, and it is usually primary care physicians who refer patients to gastroenterologists for further workup.

In the US, there are no active screening programs for esophageal cancer, in part because this is such a rare malignancy. As a result, patients do not undergo frequent endoscopies for common symptoms, such as heartburn, unless they have been diagnosed with a condition called Barrett’s esophagus, which is known to predispose patients to developing esophageal cancer. Beyond patients with this condition, endoscopy is not typically performed.

How has the incidence of select esophageal cancer subtypes changed in recent years, particularly in Western populations?

There are 2 different types of esophageal cancer seen in clinic: esophageal squamous cell carcinoma [ESCC] and esophageal adenocarcinoma. Worldwide, ESCC is the most common type of esophageal cancer. It is associated with smoking, alcohol use, and certain dietary deficiencies. In the US, however, it is quite rare. There are significant geographic variations in the incidence of this cancer.

In the US, the predominant subtype is adenocarcinoma, which typically arises in the lower part of the esophagus and frequently involves the gastroesophageal junction [GEJ], where the esophagus meets the stomach. As a result, both patients and physicians often encounter the term GEJ adenocarcinoma. Biologically, this subtype is similar to distal esophageal adenocarcinoma, and both [patient subgroups] present with similar symptoms, regardless of histologic classification.

How have treatment standards in early-stage esophageal adenocarcinoma evolved in recent years?

Staging is critically important after the initial diagnosis. As noted earlier, early-stage gastroesophageal cancer can be cured, but stage IV gastroesophageal cancer is largely incurable. After the diagnosis of esophageal cancer is made, patients typically undergo staging procedures, which include CT scans, PET scans, and endoscopic ultrasound to determine the extent of disease.

Patients with early-stage esophageal cancer may be cured, but this generally involves a multimodal approach that includes surgery, chemotherapy, and sometimes radiation. For the most common subtype in the US—esophageal adenocarcinoma—treatment standards have changed in the past year. Historically, radiation was part of standard therapy, but current practice has shifted toward treating these patients similarly to those with gastric cancer, using perioperative chemotherapy.

The recommended regimen is FLOT chemotherapy [5-fluorouracil, leucovorin, oxaliplatin, and docetaxel], which includes 3 chemotherapeutic agents administered concurrently. For ESCC, the standard of care remains chemoradiation. This includes neoadjuvant chemoradiation per the [Dutch] CROSS trial [NTR487], followed by surgical resection. Postoperatively, immunotherapy is administered to patients with residual disease at the time of resection.

How should the potential for treatment-related toxicities be weighed against symptomatic benefits when selecting therapies for patients with esophageal cancer?

Toxicities [associated with] treatment must be carefully considered when selecting the most appropriate therapy for patients. Many patients seen in the clinic do not feel well at baseline, primarily due to the burden of their disease. Patients often present with significant weight loss and symptoms like dysphagia or odynophagia, which substantially impair their QOL.

A key goal of treatment is to improve symptoms by effectively shrinking the tumor. When this is achieved, patients often experience substantial improvement in QOL, even when treatment is associated with some toxicity. This underscores the importance of objective response rate as a critical factor in selecting therapy.

Although current treatments—including chemotherapy, immunotherapy, and targeted agents like trastuzumab [Herceptin]—[are associated with] toxicity, many patients report improved well-being after just 1 or 2 cycles. For example, patients who initially present with difficulty eating may regain the ability to eat comfortably following treatment initiation, leading to a notable improvement in overall functioning and QOL.