Between 2008 and 2018, a total of 1962 patients with early BE neoplasia were referred to a BEC. A visible abnormality was detected in 1395 patients (71%) and removed with ER (Fig. 1). After ER for LGD, HGD, or LR-EAC (n = 1140), a flat BE segment remained in 1034 patients. The vast majority of these patients (91%) underwent additional ablation aimed at eradication of the entire BE segment. Ninety-four patients (9%) had ER monotherapy for LGD (n = 9), HGD (n = 23), T1a EAC (n = 47), or T1bsm1 EAC (n = 15), with remaining BE, and were included for this study.
Patients had a mean age of 74 (± 10) years and ASA classification II (67%) or III/IV (23/2%), with ER performed for LGD (10%), HGD (25%), or LR-EAC (66%) (Table 1).
Decision-Making After ER
After ER for all visible abnormalities, a flat BE segment of median C2M5 (0–5; 3–8) remained with NDBE (n = 48, 51%), LGD (n = 29, 32%), or HGD (n = 6, 6%). In 11 patients (12%), no biopsies were obtained since this was considered not to change clinical decision-making.
In 73 patients (78%), additional ablation was not started due to age and/or comorbidity. Concomitant reasons in this group were as follows: expected poor regression after RFA due to regeneration with BE after ER (n = 8, 11%); patient preference (n = 7, 10%); persistence of a small BE tongue only (n = 5, 7%); and/or complications after ER (n = 3, 4%) (Fig. 2).
In the remaining 21 patients (22%) in whom age and comorbidity played no role, reasons not to continue with ablation therapy were as follows: other treatment protocols (e.g., in the pre-RFA era) (n = 11, 52%); persistence of a small BE tongue only (n = 6, 29%); expected poor regression after RFA due to BE regeneration after ER (n = 3, 14%); complications after ER (n = 1, 5%); and/or patient preference (n = 1, 5%).
Progression During Follow-Up
During a median endoscopic FU of 21 months (11–51) with a median of 4 endoscopies 3,4,5 per patient, no patient progressed to advanced cancer. Overall, 17 patients (18%, annual progression risk 8.0% [95% CI 5.1–12.5]) progressed to HGD (n = 10) or LR-EAC (n = 7) (Table 2). The median time to progression was 26 months (23–47), and the first progression was detected 18 months after ER. All patients who progressed had undergone at least 2 FU endoscopies without abnormalities after ER.
Sixteen out of seventeen progressors were successfully treated endoscopically, either with ER for a visible lesion containing LR-EAC (n = 7) or HGD (n = 6) or with ablation therapy for flat HGD (n = 3). A single patient who progressed from LGD to HGD had no further treatment, and the patient died shortly after due to an unrelated cause. Six progressors had developed a worse histological grade during FU, than the initial histology after baseline ER. This included baseline LGD to m-EAC in FU (n = 1), baseline HGD with m-EAC in FU (n = 4), and baseline m-EAC with sm-EAC during FU (n = 1).
The annual risk for progression was 6.4% for residual NDBE and 6.7% for LGD, as compared to 14.5% for residual HGD (Table 2).
In total, 55 patients had an endoscopic FU > 18 months with an annual risk for progression of 8.6% per person year [95% CI 5.4–13.3]. The median FU in this subgroup of patients was 31 months after ER (IQR 17–53).
In the majority (27/39; 69%) of the patients with FU < 18 months, endoscopic FU was discontinued at median 3 months (IQR 0–9) after ER, due to limited life expectancy. Of these 27 patients, 15 had unrelated death median 18 months after ER, whereas the remaining 12 were alive and asymptomatic at median 55 months after ER. The remaining 12/39 patients with short FU were recently treated with ER and were still under endoscopic surveillance (median 12 months).
Our second aim was to asses all-cause mortality during long-term follow-up in the subgroup of patients with older age and/or comorbidity, to verify whether ER monotherapy was justified in this group of patients.
As reported, in 73 patients, age and/or comorbidity played an important role in the decision not to continue with ablation therapy after ER. In 37 patients, endoscopic surveillance was stopped early at median 20 months (5–59) after ER (Fig. 3). Unrelated death occurred in 16 of these patients median 10 months after FU was stopped. The remaining 21 patients were still alive and asymptomatic median 24 months after FU was stopped.
In the remaining 36 patients, endoscopic FU was not stopped early. A total of 13 patients died from unrelated causes while being under surveillance, median 50 months after ER. The remaining 23 patients were still under surveillance at the moment of data collection, median 21 months after ER.
Overall, 29 of 73 patients (40%) died due to unrelated causes median 28 months after ER at a median age of 80 (72–85) years. The remaining 44 of 73 patients were still alive at the moment of data collection median 42 months after ER. Figure 4 shows the cumulative incidence curves for progression and unrelated death. Neoplasms other than EAC (n = 11, 38%) and cardiovascular disease (n = 11, 38%) contributed the most common causes of death.
None of the 94 patients progressed to disease stages that exceeded boundaries for curative endoscopic treatment, developed symptomatic EAC, or died from EAC.
In univariable analysis, length of the residual BE was significantly associated with risk for progression during FU (Table 3). For patients with a remaining circumferential BE of 0–1 cm, 2–5, or > 5 cm, the annual progression risks were 1.8%, 7.0%, and 15.9%, respectively. The risk increased with 11% for every centimeter increase in BE length. The hazard ratio for persisting HGD versus LGD or NDBE was considerable, but did not reach the level of statistical significance. Estimated hazard ratios for Fine and Gray and Cox analysis were comparable.