Intramucosal squamous cell carcinoma of the esophagus: is surgery still an option?

Since the early 1990 s, endoscopic resection has gained acceptance as a staging procedure and a potentially curative treatment for early esophageal squamous cell carcinoma (ESCC) [1]. Limitations of the technique include: 1) the risk of lymph node metastases and distant recurrences; 2) the risk of local recurrence; and 3) the risk of metachronous recurrence.

“This is the first prospective and multicenter study on the long-term outcomes of endoscopic resection for intramucosal ESCC.”

Endoscopic resection is a valid treatment modality for early ESCC when lesions have no or only minimal risk of lymph node invasion. Provided the tumor is well differentiated and no lymphovascular involvement is seen on pathology, endoscopic resection is curative for intraepithelial lesions (T1am1) and lesions invading the lamina propria (T1am2), and potentially curative for lesions reaching the muscularis mucosae (T1am3) or the shallow submucosa < 200 µm (T1bsm1). Indeed, while the risk of lymph node metastases is < 2 % for T1a m1 – 2 ESCC, it has been reported to be > 10 % for T1am3 in several studies [2]. However, this latter figure was mainly observed in surgical series, while the rates of lymph node and organ metastases from endoscopically resected T1am3 ESCC range from 2.9 % to 8.7 % [3] [4]. This discrepancy could be explained by pathologists handling the surgically and endoscopically resected specimens differently, resulting in a relative understaging of the T stage of the surgical specimens, and by the inclusion of various proportions of T1am3 lesions with lymph node involvement and poor differentiation.

In this issue of Endoscopy, Oda et al. report the long-term outcomes of the Japan Esophageal Cohort study, which included 330 patients with endoscopically resected intramucosal ESCC across 16 Japanese centers [5]. This is the first prospective and multicenter study on the long-term outcomes of endoscopic resection for intramucosal ESCC. In 2020, the question is not whether or not intramucosal ESCC can be safely resected endoscopically by expert endoscopists, but what rates of local, metachronous, and distant recurrences one should expect after endoscopic resection of a T1a ESCC. The prospective design, the rigorous endoscopic follow-up protocol (every 3 months and every 6 months thereafter), which included computed tomography (CT) and endoscopic ultrasound (EUS), and the 49.4 months median follow-up period contribute to the robustness of the data presented. The authors included 396 lesions, with a mean size of 20.4 mm, of which 53 (16.2 %) were T1am3 lesions. They observed two cases (2/330, 0.6 %) of lymph node metastases, both in patients with T1am3 lesions (2/53, 3.8 %), with a metastatic disease course and unfavorable outcome even after rescue surgery. Unfortunately, the authors did not specify the tumor differentiation grade or the presence of lymphovascular involvement for these patients, features that we know to significantly increase the rate of lymph node metastases. However, these numbers concur with those of large retrospective series, and justify performing oncologic surveillance including CT and EUS, and possibly also positron emission tomography/CT, in the follow-up of patients with T1am3 ESCC.

The local recurrence rate was 3.9 %, and all recurrent lesions were amenable to endoscopic therapy. This number reflects the 58.8 % of lesions resected by endoscopic mucosal resection in this cohort from 2005 to 2010, resulting in a 73.5 % rate of en bloc resection. Since 2010, the increasing use of endoscopic submucosal dissection, enabling en bloc resection of ESCC regardless of the lesion size, has solved the problem of local recurrences, with local recurrence rates almost at zero [6].

ESCC can be considered as the expression of a diffuse disease of the esophageal squamous mucosa caused by well-identified risk factors, and the rate of metachronous ESCC ranges from 5 % to 10 % per year [4] [7]. In the work from Oda et al., the authors observed a 5.1 % annual rate of metachronous ESCC. In a prior report from the same patient cohort, the authors demonstrated that alcohol abstinence significantly helped to decrease the rate of metachronous ESCC (adjusted hazard ratio 0.47, 95 % confidence interval 0.25 – 0.91; P = 0.025) [7]. However, annual endoscopic surveillance remains mandatory to detect and resect metachronous recurrences [2].

Overall, the 99.1 % 5-year disease-specific survival after endoscopic resection, and the recently reported efficacy of organ-preserving strategies with chemoradiotherapy following endoscopic resection of intramucosal ESCC with poor histoprognostic features [8], compared with the mortality of surgery and the high rate of cancer recurrence after resection of N + disease, suggest that esophagectomy for intramucosal ESCC might soon belong to the past.

Publication History

Article published online:
27 October 2020

• References

• 1 Endo M. Endoscopic resection as local treatment of mucosal cancer of the esophagus. Endoscopy 1993; 25: 672-674
• 2 Pimentel-Nunes P, Dinis-Ribeiro M, Ponchon T. et al. Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2015; 47: 829-854
• 3 Katada C, Muto M, Momma K. et al. Clinical outcome after endoscopic mucosal resection for esophageal squamous cell carcinoma invading the muscularis mucosae – a multicenter retrospective cohort study. Endoscopy 2007; 39: 779-783
• 4 Yamashina T, Ishihara R, Nagai K. et al. Long-term outcome and metastatic risk after endoscopic resection of superficial esophageal squamous cell carcinoma. Am J Gastroenterol 2013; 108: 544-551
• 5 Oda I, Shimizu Y, Yoshio T. et al. Long-term outcome of endoscopic resection for intramucosal esophageal squamous cell cancer: a secondary analysis of the Japan Esophageal Cohort study. Endoscopy 2020; 52: 967-975
• 6 Takahashi H, Arimura Y, Masao H. et al. Endoscopic submucosal dissection is superior to conventional endoscopic resection as a curative treatment for early squamous cell carcinoma of the esophagus (with video). Gastrointest Endosc 2010; 72: 255-264
• 7 Katada C, Yokoyama T, Yano T. et al. Alcohol consumption and multiple dysplastic lesions increase risk of squamous cell carcinoma in the esophagus, head, and neck. Gastroenterology 2016; 151: 860-869.e7
• 8 Minashi K, Nihei K, Mizusawa J. et al. Efficacy of endoscopic resection and selective chemoradiotherapy for stage I esophageal squamous cell carcinoma. Gastroenterology 2019; 157: 382-390.e3