A session devoted to esophageal cancer at the 2011 Gastrointestinal Cancers Symposium, held January 20-22 in San Francisco, offered a look at emerging strategies from different perspectives. The main message was the need for a multidisciplinary approach that engages medical oncologists, surgeons, and radiation therapists from day 1.

Molecular Screening for Barrett's Esophagus

Increasing understanding of the molecular pathogenesis of Barrett's esophagus is paving the way for the use of molecular biomarkers to detect and risk-stratify Barrett's esophagus, according to Rebecca Fitzgerald, MD, of Hutchison/MRC Research Center in Cambridge, UK.  She and her colleagues developed a simple tool for molecular population-based screening, the "cytosponge." This is a capsule containing an expandable spherical mesh attached to a string, which is swallowed and dissolves in the stomach over 3 to 5 minutes, releasing the sponge. As the sponge is pulled back it collects cells that are assayed to define their origin as gastric cardia, squamous esophagus, or Barrett's columnar epithelium.

In gene profiling of samples from Barrett's esophagus compared with adjacent healthy tissues, they identified a potentially useful biomarker, trefoil factor 3 (TFF3). The sensitivity and specificity of this biomarker for detecting 2 cm or more of Barrett's esophagus are 90% and 94%, respectively, which is comparable to mammography for breast cancer screening, Dr. Fitzgerald said. Studies are underway in 1,000 individuals to validate this approach.

Evolution in the Surgical Management

The past decade has seen major improvements in technical approaches and surgical outcomes associated with esophageal resection for Barrett's esophagus with high-grade dysplasia, and early and locoregional cancer of the esophagus, according to Donald E. Low, MD, of Virginia Mason Medical Center in Seattle. The most significant technical evolution has been the expansion of minimally invasive esophageal resection, which about one-quarter of surgeons have adopted for esophagectomy. "Outcomes have not suffered with the introduction of minimally invasive techniques, and further review may show significant advantages," he said.

"In general, esophageal resection for cancer has earned a reputation for high mortality and morbidity, and poor postoperative quality of life," he acknowledged, "though such outcomes are strongly linked to the volume of esophagectomies done by individual surgeons and medical centers." While recent national audits have found surgical-related mortality to be 5% to 7%, dedicated, high-volume esophageal specialty centers produce perioperative mortality rates of under 2%, and enhanced-recovery programs are reducing length of stay, operative blood loss, pain, intensive-care use, and cost, he said.

"Nonsurgical practitioners should align themselves with a dedicated high-volume surgical esophageal team with a recognized record of low mortality, moderate morbidity, and long-term commitment to follow-up and recovery, as well as participation in National Clinical trials," Dr. Low suggested. "A multidisciplinary approach to staging and treatment, which will include presentation at Tumor Board, will ensure the best possible outcomes when treating all stages of esophageal cancer."

Endoscopic Treatment Options

Christian Ell, MD, of the Dr. Horst Schmidt Klinik in Wiesbaden, Germany, advocated endoscopic resection as the standard treatment of early, low-risk esophageal malignancy.  "Surgery, in my eyes, is overtreatment and a method that should be reserved," he said.

"Endoscopic treatment is associated with low morbidity rate and zero mortality, excellent long-term survival, and preservation of quality of life," he noted in his presentation. In a recent case-control study from Dr. Ell's group comparing endoscopic with surgical resection, disease-free survival and overall survival were similar for the two treatments. However, endoscopic resection was completely free of major complications, whereas the complication rate was 33% with surgery (P < .001).¹ This has held true for over 1,000 patients treated in Wiesbaden, he added.

Efficacy is also maintained with the endoscopic approach, he added. In a study of 349 patients with high-grade intraepithelial neoplasia or mucosal Barrett's cancer, complete responses were observed in 96.6%.² Survival at almost 5 years is approximately 80%, which is equivalent to the normal German population, he said.

Dr. Ell noted there are many different endoscopic techniques that involve resection and ablation, "but ablation techniques are not appropriate for the primary treatment of neoplastic Barrett's epithelium," he stressed. "The technique of choice is the 'suck and cut' resection."

Endoscopic Strategy for cN0 Superficial Carcinoma

Japanese investigators reported success with a strategy in cN0 superficial lesions. It aims for local control with endoscopic submucosal dissection first (rather than the standard, surgical resection), followed by additional treatment based on the histologic examination.³ They reviewed 140 patients diagnosed with M3-SM2 squamous cell carcinoma of the esophagus who underwent endoscopic mucosal resection or endoscopic submucosal dissection. The 83 who received additional treatment based on histology (more surgery or chemoradiotherapy) were further studied. The two-step approach was not associated with serious complications (15%, mainly stenosis), and clinical outcomes were good. Five-year relapse-free survival was 100% for patients who had additional surgery and 88% for those receiving chemotherapy; 5-year overall survival rates were 100% and 76%, reported Toshiro Iizuka, MD, of Toranomon Hospital in Tokyo. ■

References

1. Pech O, et al: Annals of Surgery. In press.

2. Pech O, Behrens A, May A, et al: Long-term results and risk factor analysis for recurrence after curative endoscopic therapy in 349 patients with high-grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett's oesophagus.  Gut 57:1200-1206, 2008.

3. Iizuka T, Kikuchi D, Hoteya S, et al: Therapeutic strategy involving endoscopic resection for cN0 superficial carcinoma of the esophagus. Gastrointestinal Cancers Symposium. Abstract 1. Presented January 20, 2011.