Low recurrence rates after R0 endoscopic resection of high-risk T1 adenocarcinoma in Barrett esophagus support a strict endoscopic surveillance strategy: preliminary results of a prospective, international, multicenter cohort study (PREFER)

Aims Optimal management following radical endoscopic resection (R0 ER) of high-risk (HR) T1 esophageal adenocarcinoma (EAC) remains a topic of debate. In this first-ever prospective international multicenter cohort study (PREFER, NCT03222635), we evaluate the safety of a strict endoscopic follow-up (FU) strategy following R0 ER of HR-T1 EAC.

Methods Submucosal (T1b) EAC patients were included from July 2017 to July 2023 at 19 hospitals across Europe and Australia. T1b EAC was considered low-risk (LR) in case of submucosal-invasion<500 µm, good-moderate differentiation, and absent lymphovascular invasion (LVI). T1b EAC was considered HR in case of submucosal-invasion≥500 µm, and/or poor differentiation, and/or LVI. From July 2020 onward, we also included HR-mucosal (T1a) EAC (i.e. poor differentiation and/or LVI) as part of an ongoing prospective registry. To ensure appropriate FU, we assessed outcomes for patients included up to July 2023, at which point inclusion for the prospective PREFER-study was completed. Patients underwent baseline re-staging with gastroscopy, endoscopic ultrasound (EUS) and CT/PET. If there were no signs of metastasis (cN0M0), patients entered strict FU with gastroscopy and EUS 3-monthly the first 2 years, 6-monthly during years 3 and 4, and annually at year 5. CT/PET was repeated 1 year after baseline. Primary outcomes were disease-specific and overall survival; secondary outcomes were rates of distant metastasis, LNM, and intra-esophageal recurrence not amenable to endoscopic treatment.

Results As of July 2023, 200 patients (166 males, median age 70 years [IQR 63-76]) were included, 157 T1b patients (n=54 low-risk (LR) T1b and n=103 HR-T1b) and 43 HR-T1a patients. For the T1b group, the majority (85%) had an uneventful median FU of 25 months (IQR 15-44). Distant metastases were diagnosed in 3/157 (2%, 95% CI 0 – 4) patients, all without local recurrence or LNM: 1/3 underwent resection of a lung metastasis, with no signs of recurrence after 15 months; 1/3 had liver metastasis and received immunotherapy but died of non-EAC cause; 1/3 had liver metastasis and refused further treatment and died of EAC. Locoregional LNM were diagnosed in 10/157 (6%, 95% CI 3 – 10). Of these 2/10 died from EAC, of whom one also had intra-esophageal recurrence but declined further treatment. The remaining patients received appropriate treatment and are disease-free after median 28 (IQR 14 – 45) months following additional treatment. In total, 10/157 patients (6%, 95% CI 3 – 10) developed intra-esophageal tumor recurrence requiring non-endoscopic treatment; 3/10 declined additional treatment and died from EAC. Furthermore, non-EAC mortality (8%, 13/157) was higher than EAC-related mortality (3%, 5/157). In the HR-T1a group, no recurrent disease was diagnosed after a median FU of 22 months (IQR 16 – 27).

Conclusions The interim results of this first-ever prospective study on HR-T1 cN0M0 EAC suggest that strict endoscopic follow-up after R0 endoscopic resection is a safe and effective management strategy.

Publikationsverlauf

Artikel online veröffentlicht:
27. März 2025