From the AGA Journals

Study eyed endoscopic submucosal dissection for early-stage esophageal cancer

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Use ESD for early-stage esophageal cancer

This study adds more evidence supporting the use of endoscopic submucosal dissection (ESD) in early esophageal cancer. Unlike esophageal adenocarcinoma, esophageal squamous cell carcinoma (ESCC) has a higher risk of lymph node metastasis and tends to be multifocal. ESCC lesions invading the submucosa (T1b) have the highest risk of lymph node metastasis (up to 60% in lesions with deep submucosal invasion).

Historically, endoscopic resection was reserved for mucosal tumors while submucosal tumors were managed surgically. Several trials have investigated the role of ESD in ESCC limited to the mucosa with excellent results. However, data for ESCC invading the submucosa (T1b lesions) are lacking. This study included 596 patients, almost half of included patients (282 patients) had T1b lesions. Although most of the T1b lesions were treated surgically (200 patients), there was a large cohort of 82 T1b ESCC lesions treated by ESD.

Interestingly, there was no difference in tumor recurrence or overall mortality in patients treated with ESD, compared with surgery for both mucosal and submucosal lesions.
Another interesting finding in this study was the use of adjuvant treatment such as radiotherapy and chemotherapy for patients treated with ESD who were found to have evidence of lymphovascular invasion. The outcome of this subset of patients was not different from patients who underwent esophagectomy. Recent evidence from this study and other published data suggest that there is a subset of submucosal ESCC lesions that can be managed endoscopically, especially submucosal lesions limited to the upper third of the submucosa. Further studies investigating the role of adjuvant treatment after ESD for deep submucosal lesions or lesions with lymphovascular invasion are needed.

Mohamed O. Othman, MD, is an associate professor of medicine, director of advanced endoscopy, and chief of the section of gastroenterology, Baylor College of Medicine, Houston. He is a consultant for Olympus and Boston Scientific.



For patients with early-stage esophageal squamous cell carcinoma, minimally invasive esophageal submucosal dissection (ESD) led to significantly fewer severe adverse perioperative events than esophagectomy and was associated with similar rates of all-cause mortality and cancer recurrence or metastasis, according to the findings of a single-center retrospective cohort study.

After a median of 21 months of follow-up (range, 6-73 months), rates of all-cause mortality were 7% with ESD and 11% with esophagectomy, said Yiqun Zhang of Zhongshan Hospital, Shanghai, China, and his associates. Rates of cancer recurrence or metastasis were 9.1% and 8.9%, respectively, while disease-specific mortality was lower with ESD (3.4% vs. 7.4% with esophagectomy; P = .049). Severe nonfatal adverse perioperative events occurred in 15% of ESD cases versus 28% of esophagectomy cases (P less than .001). The findings justify more studies of ESD in carefully selected patients with early-stage (T1a-m2/m3 or T1b) esophageal squamous cell carcinoma, the researchers wrote in Clinical Gastroenterology and Hepatology.

Esophagectomy is standard for managing early-stage esophageal squamous cell carcinoma but is associated with high rates of morbidity and mortality. While ESD is minimally invasive, it is considered risky because esophageal squamous cell carcinoma so frequently metastasizes to the lymph nodes, the investigators noted. For the study, they retrospectively compared 322 ESDs and 274 esophagectomies performed during 2011-2016 in patients with T1a-m2/m3 or T1b esophageal squamous cell carcinoma. All cases were pathologically confirmed, and none were premalignant (that is, high-grade intraepithelial neoplasias).

Endoscopic submucosal dissection was associated with significantly lower rates of esophageal fistula (0.3% with ESD vs. 16% with esophagectomy; P less than .001) and pulmonary complications (0.3% vs. 3.6%, respectively; P less than .001), which explained its overall superiority in terms of severe adverse perioperative events, the researchers wrote. Perioperative deaths were rare but occurred more often with esophagectomy (four patients) than with ESD (one patient). Depth of tumor invasion was the only significant correlate of all-cause mortality (hazard ratio for T1a–m3 or deeper tumors versus T1a–m2 tumors, 3.54; 95% confidence interval, 1.08-11.62; P = .04) in a Cox regression analysis that accounted for many potential confounders, such as demographic and tumor characteristics, hypertension, chronic obstructive pulmonary disease (COPD), nodal metastasis, chemotherapy, and radiotherapy.

Perhaps esophagectomy did not improve survival in this retrospective study because follow-up time was too short, because adjuvant therapy compensated for the increased risk of tumor relapse with ESD, or because of the confounding effects of unmeasured variables, such as submucosal stages of T1b cancer, lymphovascular invasion, or tumor morphology, the researchers wrote. “Since a randomized study comparing esophagectomy and ESD alone would not be practical, a potential strategy for future research may include serial treatments – that is, ESD first, followed by esophagectomy, radiotherapy, or chemotherapy, depending on the ESD pathology findings,” they added. “A quality-of-life analysis of ESD would also be helpful because this might be one of the biggest advantages of ESD over esophagectomy and was beyond the scope of this study.”

The study was supported by the National Natural Science Foundation of China, the Shanghai Committee of Science and Technology, and Zhongshan Hospital. The investigators reported having no relevant conflicts of interest.

SOURCE: Zhang Y et al. Clin Gastroenterol Hepatol. 2018 Apr 25. doi: 10.1016/j.cgh.2018.04.038.

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