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Commentary (Kleinberg et al): Primary Combined-Modality Therapy for Esophageal Cancer

Commentary (Kleinberg et al): Primary Combined-Modality Therapy for Esophageal Cancer

Dr. Bruce Minsky presents an excellent review of data supporting nonoperative management of esophageal cancer. He describes the data in favor of primary chemoradiotherapy without surgery and concludes that combined use of chemotherapy and radiation is the standard of care for patients found to have squamous cell cancers or adenocarcinoma. While he acknowledges the conflicting data regarding treatment of each histologic type, he argues that, for now, chemoradiotherapy is appropriate for patients diagnosed with disease of either histology.

Although we agree that the evidence of benefit for adding surgery to chemoradiotherapy is controversial, the curative potential of chemoradiotherapy alone in adenocarcinoma is not yet convincingly validated. As such, nonoperative management may not be appropriate for adenocarcinoma patients who are candidates for surgical resection. Indeed, there are no models for treating adenocarcinoma of the gastrointestinal (GI) tract that show chemoradiation to be curative without surgery. For patients with operable esophageal adenocarcinoma, combined-modality therapy should include surgery. The primary question, then, becomes whether giving concomitant chemoradiation prior to surgery improves outcome.


Histologic Differences

Because esophageal squamous cell cancers and adenocarcinomas are distinct clinical entities, they must be managed differently. Each is characterized by anatomic location (upper/midesophagus vs distal esophagus/gastroesophageal junction), pattern of first failure (local vs distant), epidemiologic risk factors (tobacco and alcohol abuse vs gastroesophageal reflux disease, obesity, and diet), and patient demographics that include age, race, and comorbid conditions. In addition, a shared general approach to treatment exists for each histology that applies no matter what the location of the lesion.

When referring to squamous cell cancers, those affecting the head and neck (eg, the larynx, oropharynx, and nasopharynx) and the anus represent paradigms for which definitive chemoradiotherapy alone results in cure and organ preservation. The first trials examining nonoperative management of esophageal squamous cell cancers began in the early 1980s. This approach was based on trials using chemoradiation against squamous cell carcinoma of the anal canal that elicited exciting results.[1-3]

In contrast, surgery is the mainstay of curative treatment for adenocarcinoma arising in all anatomic sites within the GI tract. Treatment approaches for operable stages of these GI cancers focus on determining the usefulness of neoadjuvant and adjuvant therapies. Given these fundamental differences between adenocarcinoma and squamous cell cancer, perhaps esophageal adenocarcinomas and squamous cell cancers should be considered separately when discussing surgical and nonsurgical approaches.


Strides in Treatment

Over the past decade, adenocarcinoma has come to constitute the majority of esophageal cancers treated in Western industrialized countries. For locally advanced, operable disease, comprehensive staging with computed tomography (CT), endoscopic ultrasound, and positron-emission tomography most often reveals a T2 or T3 primary with N1 regional nodes and, not infrequently, M1a-designated celiac nodal involvement. In addition to this shift toward a surgically treated histology, additional changes in the recent past support the operative treatment of adenocarcinoma.

One change noted over the years is the ongoing reduction in surgical mortality. The prior high operative mortality rate of 10% to 20% motivated the development of nonsurgical treatment of esophageal cancer in the early 1980s. Over the past decade, however, mortality rates dropped below 5% at centers with experienced surgical teams.[4-6] The reason for this success is likely multifactorial, including better patient selection, improved perioperative management, and, perhaps most intriguingly, a better operative outcome in patients with adenocarcinoma compared to those with squamous cell cancer.[7-8]


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