New Perspectives in the Management of Superficial Esophageal Cancer

Esophageal cancer, 3D illustration showing malignant tumor in the human esophagus
For large, protruding or poorly lifting lesions, researchers indicate endoscopic submucosal dissection may prove to be more efficacious.

Screening, early diagnosis, and treatment of superficial esophageal cancer is typically done using endoscopy, while endoscopic submucosal dissection (ESD) is the preferred option for the resection of superficial squamous cell neoplasia.1 For managing Barrett’s esophagus, patients are treated using a combination of endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA).1 But, for large, protruding or poorly lifting lesions, researchers indicate ESD may prove to be more efficacious.1

With esophageal cancer being the eighth most common cancer and with esophageal adenocarcinoma (EAC) arising on Barrett’s esophagus becoming more prominent in America and Northern Europe,1 researchers are examining the best ways to describe and classify types of esophageal cancer. In an effort to simplify the complex and diverse patterns of Barrett’s esophagus, the Japan Esophageal Society has created one of several recently developed classification systems, which focuses on mucosal and vascular patterns, shape, or arrangement.2

“The new classifications classify most mucosal or vascular descriptors as ‘regular’ for non-dysplastic and ‘irregular’ for dysplastic Barrett’s esophagus,” explained Ryu Ishihara, a researcher with the Department of Gastrointestinal Oncology at the International Cancer Institute in Osaka, Japan. “These simple descriptors make the classifications easy to apply in clinical practice, with acceptable sensitivity, specificity, and inter-observer agreement for the diagnosis of dysplasia in Barrett’s esophagus.”2

Diagnosing Superficial Esophageal Cancers

Patients with advanced EAC have a 5-year survival rate of 20%.2  Yet, as with most cancers, early diagnosis of superficial esophageal cancer typically leads to more favorable outcomes. However, early detection is challenging.  

Several requirements are necessary to obtain a diagnosis with an endoscopy, including the use of high-definition white light, the involvement of an experienced endoscopist, ample time for inspection, and the testing of biopsies. Researchers recommend that “en bloc endoscopic resection should remain the gold standard for the diagnosis.”1

Researchers indicate that although endoscopic ultrasound could be used to diagnose high-risk lesions (per recommendations from the European Society of Gastrointestinal Endoscopy), its use in the initial stages of diagnosing esophageal neoplasia is controversial.1 Japanese researchers, however, concluded that miniprobe endoscopic ultrasound can “be used to distinguish between mucosal and submucosal cancers, thereby improving staging accuracy.”2

Advanced endoscopic techniques other than the above-mentioned procedures have also been considered for diagnosis of Barrett’s esophagus, but “currently, no advanced endoscopic imaging technique is recommended…”1

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Treating Superficial Esophageal Squamous Cell Carcinomas

EMR — using submucosal injection, a cap, or ligator device — can treat early squamous cell carcinoma for lesions up to 15 mm in size with a 20-53% en bloc resection rate.1 However, if large lesions are fragmented before removal, “assessment of cancer invasion depth can be inaccurate.”2 Further, researchers indicate that “piecemeal resection of early neoplasia in Barrett’s esophagus is associated with a high local recurrence rate,” due to the likelihood of tissue remnants.2

ESD has treated squamous cell carcinoma with up to a 95.1% en bloc resection rate, but “no randomized study has compared EMR and ESD.”1 Since the use of ESD is not limited by the size of lesions, it has a higher en bloc resection rate. But, some drawbacks to ESD are the length of the procedure and its higher risk for complications.2

Although costly, RFA has been found safe and effective for the destroying early neoplasia in Barrett’s esophagus.¹ When treating flat, early stage squamous neoplasia, however, even seasoned endoscopists have had difficulties identifying T1a m1-2 lesions appropriate for RFA treatment.¹ Therefore, researchers do not recommend the use of RFA in early squamous neoplasia.¹

Diagnostic Tools of the Future

According to researchers, “the detection of molecular alterations of the Barrett’s epithelium could be a useful tool for risk stratification and prediction of response to therapy.”1 A recently developed transoral brush cytology device uses microarrays for extraction and diagnosis. According to the research,1 this type of technology, when combined with quantitative chain reaction testing for biomarkers and neoplastic changes, enables the following:

  • Assessment of the genetic diversity among Barrett’s cells
  • Better prediction of cells’ malignant potential
  • Development of tailored surveillance intervals
  • Early detection of molecular changes prompting ER or ablation

Treating Superficial Esophageal Adenocarcinoma

By comparison, multiband EMR was shown to be more cost-efficient and faster than cap-EMR, while both were equally safe for treatment of EAC and Barrett’s neoplasia.1 Additionally, although ESD has shown success in treating squamous cell carcinoma, it “is hardly compatible with the extensive and often multifocal nature of Barrett’s neoplasia.”1

European guidelines recommend piecemeal ER over ESD in most cases, but until more research is done, it is recommended that ESD in Barrett’s neoplasia “be limited to expert centers and selected cases, such as protruding lesions not amenable to cap or multiband EMR, lesions larger than 15 mm in size, and poorly lifting lesions or those with a high suspicion of submucosal invasion.”1

The combination of focused EMR for lesions and RFA for remaining Barrett’s mucosa has also been shown as a safe and effective treatment for neoplasia, and is considered to be the “gold standard”1 for treatment.

Is Surgery Indicated?

Surgery has been a common method for treating esophageal cancer, with an associated 5-year survival rate of 77- 88%.1 Yet, the 30% to 40% morbidity rate, the 2% to 5% mortality rate, and the 1-year decreased quality of life make ER a preferable first-line method over surgery,1 especially when considering that the surgery can cause higher postprocedural mortality and morbidity.

According to researchers, “ER is an optimal staging procedure for all T1 lesions, a curative treatment for the vast majority of T1a lesions, and a potentially curative treatment for T1b lesions with superficial invasion of the submucosa or in patients with high operative risk.”1

Treatment Tools of the Future

Researchers report that epithelium-regenerating, anti-inflammatory or antifibrotic drugs or devices designed to prevent postendoscopic esophageal stricture are under development.1 The evolution of novel treatment tools, such as argon plasma coagulation with submucosal lifting and cryoablation balloons, increases the possibility for “single-step ER of large esophageal neoplasms or of the complete Barrett’s esophagus.”1


1. Barret M, Prat F. Diagnosis and treatment of superficial esophageal cancerAnn Gastroenterol. 2018;31(3):256-265.

2. Ishihara R, Goda K, Oyama T. Endoscopic diagnosis and treatment of esophageal adenocarcinoma: introduction of Japan Esophageal Society classification of Barrett’s esophagus. J Gastroenterol. 2019;54:1-9.