Introduction

Metastatic recurrence rate was reported to be about 5.0% during followed up in patients with pathologically-diagnosed esophageal squamous cell carcinoma (ESCC) invading the muscularis mucosae (pT1a-MM) without lymphovascular invasion (LVI) after endoscopic resection (ER). However, these previous reports' evidence was unreliable because of insufficient careful follow-up and non-standardized pathological diagnostic procedures. Furthermore, the Endoscopic Submucosal Dissection/Endoscopic Mucosal Resection Guidelines for Esophageal Cancer published by the Japan Gastroenterological Endoscopy Society stated that recommendation of the administering additional treatment after ER could not be determined for patients with pT1a-MM ESCC without LVI.

Aims & Methods

The aim of this study was to clarify the long-term outcome of patients after ER for pT1a-MM ESCC without LVI under the central pathological review and periodic and careful follow-up. 47 institutions belonging to the Gastrointestinal Endoscopy Study Group in the Japan Clinical Oncology Group were participated in this multicenter retrospective study. Key inclusion criteria were as follows:
1) patients who underwent ER between January 2008 and December 2015,
2) ≤ 80 years of age,
3) pathologically diagnosed as pT1a-MM ESCC without LVI and vertical margin negative in each institution,
4) cN0M0, and
5) followed up for longer than 12 months after ER, and
6) available slide for central pathological review.
The following patients were excluded;
1) a history of any stage II-IV cancers within 5 years before ER, and
2) a history of pT1a-MM or deeper ESCC.
We evaluated the cumulative recurrence rate (CRR), overall survival (OS), recurrence-free survival (RFS) according to the additional treatments after ER (observation, chemoradiotherapy (CRT), and surgery). Lymph node and/or distant recurrence were included events in CRR. In addition, the central pathological review was performed in the observation group, and CRR was evaluated according to central diagnosis. This study was approved by the ethics committee in each institution.

Results

In total, 540 patients enrolled in this study, consisted of 457 male (84.6%) and median age of 67 years (range 39-80). Of these, 485 (89.8%) were observed, 45 (8.3%) were treated with CRT, and 10 (1.9%) were performed with surgery after ER. During the median follow-up of 7.0 years (IQR 5.4-8.8), the 5-year CRRs of the observation, CRT, and surgery groups were 4.9%, 2.2%, and 10.0%, respectively. In addition, the 5-year OS/ RFS were 93.1%/ 89.6% in the observation group, 93.3%/ 91.1% in the CRT group, and 100%/ 90.0% in the surgery group, respectively. Of 31 patients with metastatic recurrence, 14 died from ESCC. The central pathological review using hematoxylin and eosin-stained slides in the observation group showed that 358 (75.2%) of 476 cases, excluding 9 cases that could not be well evaluated, were concordant (diagnosed as pT1a-MM without LVI). In the remaining 118 cases, 56 (11.8%) were diagnosed as pT1a-LPM without LVI, and 62 (13.0%) were diagnosed as containing LVI or pT1b-SM. The 5-year CRR was 4.9% in pT1a-MM without LVI, 1.8% in pT1a-LPM without LVI, and 8.3% in pT1a with LVI or pT1b by the central pathological review, respectively.

Conclusion

This multicenter retrospective study of a large number of patients revealed that pT1a-MM ESCCs without LVI after ER could develop certain metastatic recurrence. In addition, the central pathological review could correctly stratify the risk of recurrence, and the standardization of the pathological evaluation for the tumor depth and LVI is needed.

Disclosure

JFE（The Japanese Foundation for Research and Promotion of Endoscopy) Grant