Barrettʼs esophagus – screening or surveillance, and what about the quality of endoscopy?

Barrettʼs esophagus (BE) is a precancerous condition; the annual risk of developing esophageal adenocarcinoma (EAC) in patients without dysplasia is 0.12 %–0.2 % [1]. Therefore, among 500 to 700 patients with nondysplastic BE, one patient will develop cancer during 1 year of follow-up. Because of this cancer risk, which is however much lower than was historically assumed (1 %–3 %/year), all patients with BE should undergo endoscopic surveillance. The aim of surveillance is the early diagnosis of Barrett’s esophagus-related neoplasia, meaning cancer, and high or low grade dysplasia (HGD/LGD). If diagnosed early, Barrett’s esophagus-related neoplasia can be treated (and cured) using minimally invasive endoscopic treatment, consisting of endoscopic resection techniques (e. g. endoscopic submucosal dissection) or ablation techniques (e. g. radiofrequency ablation). The aim of endoscopic treatment is to eliminate both the neoplasia and the BE.

“Both the neoplasia detection rate at index endoscopy and the rate of post-endoscopy (interval) neoplasia, if validated, might well serve as quality benchmarks to measure our endoscopic performance in patients with BE.”

Several guidelines dealing with the management of patients with BE recommend a number of measures, with the aim of reliably detecting neoplasia [2]. These include, among others: (a) adhering to the Seattle biopsy protocol (four quadrant biopsies every 1–2 cm + biopsies from all visible lesions); (b) using endoscopes with high definition imaging quality; (c) observing the BE segment carefully – the minimal duration of endoscopy should be 7 minutes, with at least 1 minute/1 cm of the BE segment; (d) using chromoendoscopy with acetic acid or virtually (e. g. narrow-band imaging); (e) using the validated Prague and Paris classifications; (f) collaborating with expert pathologists. These measures have been recommended even though we lack the evidence that adhering to them improves clinical outcomes. The only exception to this is the Seattle protocol, as it has been shown that, the more endoscopists who follow the protocol, the more neoplasia is detected [3].

Unlike for colorectal cancer (CRC) screening and surveillance, the topic of validation of quality indicators, including benchmarking, in the field of BE surveillance is still in its infancy. As the incidence and prevalence of CRC is eight times higher than that of EAC, we have not been in any hurry but, in view of the steadily increasing incidence of EAC, this issue is gaining importance.

In this issue of Endoscopy, Desai at al. publish a systematic review and meta-analysis of 11 studies with 59 795 patients [4]. The study assessed the rate of interval (post-endoscopy) neoplasia after a negative index endoscopy in patients with BE. The authors, inspired by definitions used in the field of CRC surveillance, and in accordance with the recent consensus statements from an International Expert Panel [5], defined neoplasia (EAC/HGD) found at or within 6 months after a negative endoscopy as prevalent, neoplasia detected prior to the next surveillance endoscopy (7 months–3 years) as interval (missed), and neoplasia diagnosed at or after 3 years as incident. A total of 1237 patients (2 % of the total cohort) were diagnosed with neoplasia (EAC/HGD). The pooled incidence rates of prevalent neoplasia, interval neoplasia, and incident neoplasia were 4.8 %, 0.5 %, and 1.4 %, respectively. When considering only neoplasia diagnosed between the index endoscopy and 3 years (prevalent and interval), 97 % of cases were detected within 6 months, while interval neoplasia accounted for only 3 %.

These results are consistent with two previous studies, which found the neoplasia detection rate (EAC/HGD) at index endoscopy to be 4.5 %–7 % (prevalent EAC/HGD may be expected in 10–20 endoscopies when BE is diagnosed at screening) [6,7]. Both the neoplasia detection rate at index endoscopy and the rate of post-endoscopy (interval) neoplasia, if validated in the future, might well serve as quality benchmarks to measure our endoscopic performance in patients with BE.

Another take-home message is that the majority of Barrett’s esophagus-related neoplasia is found at index endoscopy or within the first 6 months. This indicates the need to perform high quality initial diagnostic endoscopy in patients with BE. In addition, if the first endoscopy is not performed ideally (e. g. biopsy protocol could not be completed owing to bleeding, presence of active esophagitis), it should be repeated within 6 months. In the Czech Republic, it is even recommended that two initial endoscopies with biopsies be performed within 6 months in every patient with newly diagnosed BE. Only if no lesion or dysplasia is detected, does the patient enter standard surveillance. The third take-home message is that incident neoplasia (beyond 3 years) does occur and endoscopic surveillance is therefore justified.

Other studies have looked at these parameters, even if the definitions of prevalent, interval, and incident cancers have significantly differed from those used in the study of Desai et al. A recent retrospective US cohort study with 50 817 patients found a total of 366 EACs (0.7 % of all patients) and most of these cancers were prevalent (67 %), followed by incident (19 %), and interval (14 %) [8]. A recent meta-analysis (52 studies; 145 726 patients) found a pooled proportion of post-endoscopy (interval) cancers to be 21 %, but unfortunately this analysis did not differentiate between interval and incident EAC [9].

To summarize, the majority (97 %) of Barrett’s neoplasia (EAC/HGD) is diagnosed outside surveillance – usually during the first endoscopic examination. The likelihood of finding neoplasia (EAC/HGD; i. e. the neoplasia detection rate) at the index endoscopy is around 4 %–7 %. Interval (missed, post-endoscopy) neoplasia accounts for only 3 % of all neoplasia found in patients with BE. These values may be used as quality indicators in future studies. Furthermore, we should probably concentrate more on screening instead of surveillance because this could decrease the rate of cancers diagnosed at an advanced stage. Further research should also focus on the clinical significance of interval neoplasia – whether its better detection will be paralleled by decreased mortality or cancer diagnosis at an earlier stage. Of note, not all interval neoplasia should be considered “missed,” because hypothetically some interval cancers may be attributed to rapidly growing aggressive cancers.

Finally, preventing EAC is not only a question of good endoscopy. To prevent the development of BE or Barrett’s esophagus-related neoplasia, we should adequately treat patients with gastroesophageal reflux disease. Furthermore, all patients with BE (with or without symptoms) should receive antisecretory treatment as this has been shown to decrease the risk of developing adenocarcinoma. In addition, if neoplasia is detected, these patients should be referred to an expert center to receive appropriate treatment and post-treatment surveillance.

Publication History

Article published online:
30 May 2022

• References

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