LOW RECURRENCE RATES AFTER ENDOSCOPIC RESECTION (R0) OF HIGH-RISK T1 ADENOCARCINOMA IN BARRETT’S ESOPHAGUS SUPPORT A STRICT ENDOSCOPIC SURVEILLANCE STRATEGY: PRELIMINARY RESULTS OF A PROSPECTIVE, INTERNATIONAL, MULTICENTER COHORT STUDY (PREFER)

INTRODUCTION
Optimal management following radical endoscopic resection (R0 ER) of T1 esophageal adenocarcinoma (EAC) is still a matter of debate due to conflicting reports on the risk for lymph node metastases (LNM). In case of histological risk factors for LNM, i.e. submucosal invasion, a/o poor differentiation, a/o lympho-vascular invasion (LVI), additional treatment with esophagectomy is often still recommended. In this prospective international multicenter cohort study (NCT03222635), we aim to evaluate the safety of a strict endoscopic follow-up (FU) strategy following R0 ER for T1b and high-risk T1a EAC.

METHODS
In 19 hospitals in Europe and Australia, we included patients who underwent radical ER for a high-risk T1a EAC (poor differentiation, a/o LVI), low-risk T1b (submucosal invasion <500 um, well-moderate differentiation, no LVI) and high-risk T1b (sm-invasion ≥500um, a/o poor differentiation, a/o LVI).

After ER, patients underwent re-staging with endoscopic ultrasound (EUS) and CT/PET. If there were no signs of LNM or distant metastases, patients were consented for strict endoscopic FU, with gastroscopy and EUS every 3 months during years 1 and 2, every 6 months during years 3 and 4, and at year 5. CT/PET was repeated after 1 year. Primary outcome parameters are 5-year disease-specific and overall survival; secondary outcome parameters are rates of distant metastasis, LNM, and local recurrence ineligible for endoscopic re-treatment.

RESULTS
Since July 2017, 143 T1b patients (118 men, 69 ±9 yrs, 95 high-risk T1b, 48 low-risk T1b) were included. Median follow-up was 19 (IQR 8-33) months. 1/143 (0.7%, 95%CI 0-2.1) patient was diagnosed with a distant pulmonary metastasis that was resected with selective surgery (Table). 9/143 (6%, 95%CI 2.3-10.3) were diagnosed with LNM. All were detected at a curable stage, but 1/9 declined surgery and eventually died from EAC. 7/143 patients (5%, 95%CI 1.3-8.5) developed an intra-luminal tumor recurrence ineligible for endoscopic re-treatment, of which 2/7 declined additional esophagectomy and eventually died from EAC. 7/143 (5%) died during FU due to unrelated causes.

Since July 2020, 41 HR-T1a patients (36 men, 70 ±8 yrs) were included. After median FU of 8 (IQR 2-17) months, no patients in this subcohort were diagnosed with recurrent disease.

CONCLUSION
Our preliminary findings support a strict endoscopic FU strategy in selected patients who underwent radical ER for high-risk T1 EAC with no signs of metastatic disease (cN0M0) at baseline. In our cohort, 9% (95%CI 5-13) of patients was diagnosed with metastasis or invasive intra-luminal recurrence during FU, of which the vast majority (16/17) were still diagnosed at a curable disease stage. Non-EAC-related mortality (4%) was higher than EAC-related mortality (1.6%).