Managing Esophageal Cancer Via Nonsurgical Methods

Q: Do All Patients With Esophageal Cancer Require Surgery or Can Some Be Managed With Nonsurgical (Endoscopic, Oncologic, Etc) Methods Alone?

Issue: September 2015

ByRobin B. Mendelsohn, MD

ByChristopher J. DiMaio, MD

A: The incidence of esophageal cancer has increased in recent years. The American Cancer Society estimates that there will be 16,640 new cases and 14,500 deaths from esophageal cancer in the United States in 2010. Though it is a relatively rare cancer, it is an aggressive and lethal cancer with an overall 5-year survival rate ranging from 5% to 50%.

The diagnosis of esophageal cancer is usually confirmed by endoscopy with biopsy. There are 2 main types of esophageal cancer: adenocarcinoma (AC), which is often associated with gastroesophageal reflux disease and Barrett’s esophagus (BE), and squamous cell carcinoma (SCC), which is often associated with tobacco and alcohol use. Other rare types include small cell carcinoma, leiomyosarcoma, lymphoma, and gastrointestinal stromal tumor (GIST).

Once you have made the diagnosis, the next step is to attempt to stage the tumor to determine the extent of involvement of the esophageal wall as well as to evaluate whether the tumor has spread to local tissues or other organs. Though there is debate as to which tests to use, most experts advocate computed tomography (CT) of the chest and abdomen to assess for local and distant metastasis and endoscopic ultrasound (EUS) to assess degree of tumor invasion in the esophageal wall and to evaluate for the presence or absence of regional lymph node involvement. This strategy gives the most accurate overall staging information.

You can then individualize treatment options based on disease histology, disease stage, patient comorbidities, and patient preference. Options include surgery, endoscopic therapies, chemotherapy, radiation, or a combination thereof. Traditionally, surgery was the mainstay of treatment for cure and palliation. Esophagectomy, however, has low cure rates and is associated with significant morbidity and mortality even in expert hands. Therefore, many are moving toward a multidisciplinary approach in an attempt to provide patients with more options in a controlled and semi-standardized manner.

Figure 1. EMR removal of a stage I esophageal cancer using a fitted cap device. The lesion is brought into the cap and removed with a hot snare. Resection in this case was complete.

Figure 2a. Pretreatment endoscopic images of a patient with locally advanced esophageal adenocarcinoma involving the cardia of the stomach as well.

Figure 2b. Endoscopic images of the same patient following chemoradiation therapy showing marked improvement.

Surgery remains the standard of care for early stage cancers (stage I, tumor invades lamina propria or submucosa). The alternative options to surgery include endoscopic mucosal resection (EMR), EMR followed by chemoradiotherapy, endoscopic ablative techniques, and definitive chemotherapy, radiation, or combined chemoradiation.

EMR is a technique whereby the target lesion is lifted away from the submucosa by either using a submucosal fluid injection or by raising the lesion with a cap or band-assistive device. The target lesion is then removed with a hot snare (Figure 1).

EMR was first described in the esophagus by Mukuuchi in Japan in 1988 and has been adopted by Western centers during the past 2 decades. There are two main characteristics that make a lesion amenable to EMR. The first is that it does not infiltrate the deep layers of the esophageal wall. This is based on surgical data that demonstrated that patients who underwent curative surgeries for early stage esophageal cancers had virtually no or minimal risk of metastasis if the lesion was confined to the mucosa or lamina propria, a 10% risk if the lesion reached the muscularis mucosa or the upper submucosa, and up to 50% risk if the lesion showed deep invasion of the submucosa. Therefore, only mucosal lesions are usually considered for EMR for potential of cure. That being said, submucosal lesions can be technically removed by EMR and may be considered in patients who refuse surgery or who are not surgical candidates, with the understanding that those lesions carry a higher risk of metastasis. The second characteristic is that the lesion should not exceed two-thirds of the circumference of the esophagus. This is because circumferential mucosal resection carries a risk of post-procedure stricture formation. Most of the studies of EMR were performed in Japan with SCC and demonstrated at least comparable outcomes to surgery with much less morbidity and virtually no mortality. Though the data for EMR with AC are more limited, there is emerging evidence that this technique has similar outcomes to the SCC group.

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A second nonsurgical option is EMR followed by prophylactic chemoradiation for possible lymph node metastasis. This can be considered in patients whose lesions invade the muscularis mucosa or the upper submucosa because, as mentioned above, these patients have a higher risk of lymph node metastasis. There are currently prospective trials going on to further investigate this approach. To date, this has only been studied in SCC.

A third option is endoscopic ablation via either cryoablation, radiofrequency ablation (RFA), or photodynamic therapy (PDT). Cryoablation involves spraying liquid nitrogen at low pressure though an endoscopic catheter. Preliminary data show that this is safe and effective for the eradication of BE and early esophageal cancers. Further long-term studies are needed. Similarly, RFA employs the use of specially designed balloons and catheters to allow targeted delivery of ablative energy to the tumor. Again, early studies are promising, but further data are needed. Photodynamic therapy uses photosensitizing agents, laser light, and reactive oxygen species to endoscopically destroy the cancer cells. PDT has been proven effective and actually provides the deepest tissue destruction of the ablative therapies, but has fallen out of favor due to a relatively high complication rate, most notably photosensitivity-related skin burns and postprocedure strictures.

Definitive chemoradiation is also an option. Studies out of Japan have shown excellent response and survival rates for patients with stage II SCC receiving 5-fluorouracil (5-FU) and cisplatin and concurrently receiving external beam radiation. Similarly, a randomized study done in the United States (RTOG 85-01) looked at patients with SCC or AC and randomized them to chemotherapy with 5-FU and cisplatin and radiation, or radiation alone, and found a significant improvement in both median survival and 5-year survival in the combination group. This study included patients with stage I to III cancers, but found a significant benefit in all three stages.

Figure 3. Stage IV esophageal cancer treated via a self-expanding metal stent.

For stage II and III disease (tumor invading beyond the muscularis propria, with regional lymph node metastasis), definitive chemoradiotherapy remains the most commonly employed nonsurgical option based on the RTOG study described previously (Figure 2). In the past, many patients who responded to neoadjuvant chemoradiation went on to esophagectomy. Increasing evidence shows that chemoradiation alone may produce equivalent results.

For patients with stage IV disease (distant metastasis), most treatments are palliative interventions for dysphagia, bleeding, and pain control. Endoscopic modalities for dysphagia include laser therapy, balloon dilation, and placement of self-expanding metal stents (Figure 3). In some cases, placement of percutaneous endoscopic gastrostomy or jejunostomy tubes may be necessary for adequate nutrition. Radiation, chemotherapy, and combined chemotherapy have been used for palliation of both dysphagia and bleeding.

Conclusion

Esophageal cancer can be managed with nonsurgical methods including endoscopy, chemotherapy, radiation, or a combination of modalities. Treatment should be individualized, based on the stage of the cancer, patient comorbidities, and patient preference.

Excerpted from:

References:
American Cancer Society. Cancer Facts & Figures 2010. Atlanta, GA: American Cancer Society; 2010.
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