Until recently, patients with esophageal cancer were treated with esophagectomy, or removal of the affected part of the esophagus and surrounding lymph nodes, followed by reconstruction. Barrett esophagus with high-grade dysplasia, which carries a substantial risk of progressing to cancer, was treated the same way. However, esophagectomy leads to significant lifestyle changes, including diet limitations and an inability to sleep horizontally; and the operation itself can be dangerous for some older patients. Now, an increasing number of patients with early-stage esophageal cancer or dysplastic Barrett esophagus can be effectively treated with esophagus-sparing surgery and/or ablation.
Physicians at The University of Texas MD Anderson Cancer Center are incorporating new modalities in the diagnosis, treatment, and prevention of esophageal cancer. Among the new treatments is the use of local therapy administered endoscopically to remove early-stage tumors or dysplastic cells while preserving the esophagus.
“Around 2007, we began a program here at MD Anderson of performing local therapy for early esophageal disease,” said Wayne Hofstetter, M.D., a professor and the director of the esophageal surgery program in the Department of Thoracic and Cardiovascular Surgery. “We perform ablation for precancerous conditions and endoscopic mucosal resection followed by ablation for early-stage cancers.”
To determine the appropriate course of treatment, patients with suspected esophageal cancer or dysplastic Barrett esophagus are given a thorough staging workup. This workup usually includes endoscopic ultrasonography to identify tumor tissue, determine how deep the tumor extends into the esophageal wall, and determine whether the disease involves the lymph nodes.
If needed, advanced endoscopic imaging techniques are used to identify areas of dysplasia within an esophageal segment affected by Barrett esophagus, a precancerous lining that develops owing to exposure to acid or bile. One such method is confocal endomicroscopy. “Confocal endomicroscopy is like doing a live pathological exam; you insert a probe through the endoscope, and you can see the actual cells,” said Marta Davila, M.D., a professor in the Department of Gastroenterology, Hepatology, and Nutrition. Another such method is volumetric laser endomicroscopy, which visualizes metaplastic glands (i.e., Barrett glands) buried under normal mucosa in the esophagus.
Endoscopic mucosal resection
Patients with esophageal tumors that appear superficial on workup can undergo endoscopic mucosal resection (EMR), a definitive resection in which the esophagus is accessed via the mouth and pharynx.
EMR avoids a full-thickness injury to the esophagus and is easier for patients to withstand than open surgery. Whereas open esophagectomy is a 6-hour operation that requires a significant amount of physiological reserve and several days of postoperative recovery in the hospital, EMR is an outpatient procedure that requires patients to tolerate only 45 minutes of anesthesia and is associated with a better quality of life.
To be effective, EMR must be performed at a level of care that is not widely available. “EMR requires expertise with a scope,” Dr. Hofstetter said. “It requires a lot of experience with esophageal cancer, knowing where to cut and where not to cut, how deeply to cut, and how aggressive to be.”
Whether EMR is therapeutic, i.e., does not need to be followed by esophagectomy, is determined by pathological interpretation of the resected tissue. If pathological analysis shows that the tumor is limited to the mucosa or very superficial submucosa, is less than 2 cm wide, does not invade any blood vessels, and has been removed with negative margins, then the patient has a good chance of a complete cure without surgery. But if pathological analysis shows otherwise, the patient will likely need to undergo esophagectomy.
The experience of the esophageal surgery program led Dr. Hofstetter and his colleagues to rewrite the Society of Thoracic Surgeons’ guidelines for treating early-stage esophageal cancer in 2013; the former gold standard of esophagectomy has been replaced by EMR combined with ablation. The National Comprehensive Cancer Network guidelines also now designate EMR as a standard therapy for early-stage disease.
Endoscopic ablation is used as an adjuvant to EMR for patients with superficial tumors or as the sole treatment for patients with dysplastic Barrett esophagus whose disease is not nodular. One of two ablation modalities may be used. The first, radiofrequency ablation, delivers heat energy to the lining of the esophagus, leading to tissue destruction. Radiofrequency ablation can be administered by a balloon catheter, by a metal plate mounted at the tip of an endoscope, or by other devices. The second modality, cryoablation, uses cold gases, such as liquid nitrogen or carbon dioxide, dispensed from the end of a probe to freeze and kill abnormal cells.
The ablation modality chosen for a specific patient depends on the anatomy and the characteristics of the Barrett segment. “If we are dealing with a flat area of Barrett esophagus, we prefer radiofrequency ablation,” Dr. Davila said. “If there is mild nodularity to the area and cancer has been excluded by previous EMR, we may prefer cryoablation, which can go slightly deeper than the mucosa and into the submucosa.” Cryoablation is also used in patients in whom radiofrequency ablation failed.
Patients who have undergone EMR and do not need esophagectomy typically undergo three or four ablation sessions spaced 2–3 months apart. These ablations completely eradicate remaining dysplasia and Barrett esophagus, resulting in a new growth of healthy squamous epithelium, in 92%–93% of patients treated at MD Anderson.
Patients with Barrett esophagus with low- or high-grade dysplasia but no tumor nodule usually forgo EMR and proceed directly to endoscopic ablation. Dr. Davila noted that 10 years ago, many such patients—those with high-grade disease, and hence a high risk of progression to cancer—would have been advised to undergo esophagectomy. “Ablation has completely changed the way we manage this disease,” she said. “It’s been revolutionary.”
In the future, esophagus-preserving therapy could be extended to more types of patients with esophageal cancer. For example, patients with regional extension of cancer to the lymph nodes, which is currently treated with esophagectomy, could receive local therapy with EMR plus ablation within the esophagus and surgery or chemoradiation for the affected nodes.
Also on the horizon are systemic therapies in new combinations. Dr. Hofstetter said, “We’re trying to find ways of pushing patients’ response to medical therapy or chemoradiation to the point where they don’t need surgery.”
Technological advances also are refining best practices. Dr. Davila described a new cryoballoon ablation tool recently adopted at MD Anderson and a few other centers. The device is a through-the-scope balloon catheter that is simultaneously inflated and cooled by nitrous oxide delivered from a disposable handheld unit. The balloon can be particularly useful in narrow areas that are difficult to navigate with other ablation devices.
Overall, the esophageal surgery program at MD Anderson has brought focus to first-line strategies in managing esophageal cancer and continues to seek better up-front choices for patients with early disease. “We always say that our first shot at cancer is our best shot,” Dr. Hofstetter said.