Gastrointestinal Endoscopy
Volume 68, Issue 5 , Pages 856-858, November 2008

Any role for endoscopy screening or surveillance for esophageal adenocarcinoma among persons with GERD?

Unit of Esophageal and Gastric Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

Article Outline

 

Endoscopic screening to detect Barrett's esophagus might be warranted only among persons who have a combination of the strongest known risk factors for esophageal adenocarcinoma (ie, male sex, older age, severe reflux symptoms, and obesity).

After the strong and dose-dependent association between gastroesophageal reflux symptoms and risk of esophageal adenocarcinoma was established,1 the potential benefit of screening or surveillance endoscopy strategies gained increased interest. Yet, although a strong relative risk among reflux symptoms, obesity, male sex, older age, and this cancer was identified, no clinical recommendations for increased endoscopy were made because the incidence of esophageal adenocarcinoma was too low and the number of persons needed to follow up was unfeasibly high, at least in Sweden.2 The 5-year survival rate of less than 15% of patients with an invasive esophageal adenocarcinoma3 has, however, prompted an intensified research of potential benefits of endoscopic screening and surveillance to make early cancer detection possible (ie, in a stage at which such cancers could be curable).

In the current issue of Gastrointestinal Endoscopy, Rubenstein et al4 report results of their study by use of a computerized database of the Department of Veterans Affairs in the United States in which endoscopy conducted at least 1 year before a diagnosis of esophageal adenocarcinoma seemed to be associated with a less advanced cancer stage compared with patients in which no such endoscopy had been conducted. However, in their study, selection or detection bias from early cancer symptoms cannot be ruled out as the entire explanation for this finding. Nevertheless, there was no improvement in prognosis regardless of whether such prior endoscopy was undertaken. The lack of any survival advantage might be due to the aggressiveness of esophageal cancer and early cancer detection seems to have been rare. Rubenstein et al are to be complimented for their illuminating discussion regarding several problems in scientific evaluations of benefits of screening and surveillance. Moreover, the authors present an extensive and initiated declaration of the main limitations of their own study, which in my mind can be used as a good example of how to present a discussion, particularly in a research area with inherent methodologic difficulties. The main sources of error include the uncertainty about the quality of the endoscopies, the lack of uniform intervals between the endoscopies in persons under surveillance, lack of information about any endoscopies conducted outside the Veterans Affairs' medical system, unmeasured confounding (which can only be fully addressed in randomized controlled trial), and limited statistical power in some analyses. The main finding, a lack of improvement in survival among persons who have undergone endoscopies before the diagnosis of esophageal adenocarcinoma, cannot be explained by lead-time bias, which is otherwise a severe problem in observational studies that report survival improvement among persons with prior endoscopy. Thus, the study provides no obvious benefit of a previous endoscopy for the purpose of identifying curable esophageal adenocarcinomas.4

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Screening for esophageal adenocarcinoma? 

Screening is used for early identification of a severe disease, yet a disease that lacks any symptoms or signs, in a defined sample of the population. The benefit of such an effort is highly dependent on the prevalence of the disease screened for. Because of its low incidence and poor survival rate, the prevalence of esophageal adenocarcinoma is likely very low in any population sample without cancer symptoms. Although reflux symptoms are readily identified in the population and such symptoms are linked with an increased risk of esophageal adenocarcinoma, because of the low prevalence of this cancer it is unlikely that a defined sample of the population with a high enough prevalence to motivate a true screening strategy of esophageal adenocarcinoma alone will be generally recommended. If the rapidly increasing incidence of this cancer continues, it might, however, change the role of endoscopy screening in the future.

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Screening for Barrett's esophagus? 

The considerably higher prevalence of the chronic and premalignant condition Barrett's esophagus, estimated to be 1.6% in an endoscopy survey,5 should make screening strategies in persons with a combination of risk factors of this condition more fruitful compared with screening for esophageal adenocarcinoma. The clinical relevance of this condition is limited to the strong association with esophageal adenocarcinoma, and thus screening for Barrett's esophagus is meaningful only if further surveillance regarding development of esophageal adenocarcinoma is warranted. “Once-in-a-lifetime endoscopy” to identify Barrett's esophagus among persons with reflux disease has been suggested, but such strategy is very costly and unfeasible until the group considered for screening and subsequent surveillance is better defined. An analysis of once-in-a-lifetime endoscopy showed that is might be cost-effective only if male and white persons with chronic reflux disease are considered and if subsequent surveillance is limited to those with dysplasia of Barrett's esophagus.6

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Surveillance of Barrett's esophagus for early identification of esophageal adenocarcinoma? 

The strongly increased relative risk of esophageal adenocarcinoma among persons with Barrett's esophagus, the poor prognosis of esophageal adenocarcinoma, and its increasing incidence has prompted recommendations of endoscopy surveillance of patients with Barrett's esophagus.7 Such surveillance requires repeated endoscopies, often over long periods of time. Although cancers identified by surveillance of Barrett's esophagus are at earlier stages than those diagnosed without prior endoscopic evaluation, surveillance failures are common and recommendations for surveillance are not evidence based and unlikely to alter overall mortality rates from esophageal adenocarcinoma.8 The knowledge of the true absolute risk for development of an esophageal adenocarcinoma during such surveillance is the key to the question whether surveillance is worthwhile rather than the relative risk. Previous follow-up studies of persons with Barrett's esophagus reported substantial risk of cancer development, whereas more recent and larger studies with longer follow-up seems to indicate that the rate of progression from a Barrett's mucosa to an invasive adenocarcinoma is lower than previously suspected.9 Some data suggest that surveillance only of patients with dysplasia might be warranted6 or even only among those with high-grade dysplasia because risk for development of esophageal adenocarcinoma among patients with low-grade dysplasia seems to be low.10

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Problems with endoscopy screening and surveillance of Barrett's esophagus 

About 15% of the adult population in Western societies has reflux disease, according to recently agreed-on definitions.11 This high prevalence makes it unfeasible to perform screening endoscopy in the general population with such disease. Such efforts would rapidly exceed the available health care resources. Endoscopy surveillance of all persons with an identified Barrett's esophagus would also require extensive costs and cause considerable suffering among the persons included in such programs because it must be acknowledged that endoscopies are unpleasant experiences for most patients, and complications do occur. Moreover, inclusion in such surveillance program does often introduce a constant anxiety of possibly getting a disease with a poor prognosis whenever detected. Another problem of screening and surveillance is the question whether the treatment of the disease under study is curative. The standard treatment of esophageal adenocarcinoma is esophagectomy, which is a highly extensive surgery with considerable risk of severe complications12 and with a long-standing deterioration in the health-related quality of life.13 Moreover, the population-based long-term prognosis is poor in an unselected sample.14 For high-grade dysplasia in a Barrett's esophagus, however, the endoscopic treatment with mucosal resection15 or photodynamic therapy16 might be a better option. Because such therapy can also be used for older persons, these might no longer be excluded from potential surveillance, further expanding the population that should be considered for surveillance.

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The future of endoscopy screening and surveillance 

In the future it should be highly valuable to tailor any screening or surveillance strategies to allow more effective identification of esophageal adenocarcinoma in a curable stage. Endoscopy screening to detect Barrett's esophagus only might be warranted only among persons who have a combination of the strongest known risk factors for esophageal adenocarcinoma (ie, male sex, older age, severe reflux symptoms, and obesity17). The future role of endoscopy surveillance might be limited to patients with dysplasia or even only to those with high-grade dysplasia.

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Reduced mortality in esophageal adenocarcinoma? 

Research that can identify preventable risk factors or measures that can counteract progression of premalignant mucosa (ie, Barrett's esophagus) is probably a more successful strategy to reduce the overall death and suffering from esophageal adenocarcinoma globally. However, a continued role of endoscopy screening and surveillance to decrease the mortality cannot be ruled out, particularly if such efforts can be better tailored to smaller true high-risk groups in the future.

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Disclosure 

The author reports that there are no disclosures relevant to this publication.

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References 

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  15. Picasso M, Blanchi S, Filiberti R, et al. Mucosectomy for high-grade dysplasia in Barrett's esophagus. Minim Invasive Ther Allied Technol. 2006;15:325–330
  16. Prasad GA, Wang KK, Buttar NS, et al. Long-term survival following endoscopic and surgical treatment of high-grade dysplasia in Barrett's esophagus. Gastroenterology. 2007;132:1226–1233
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PII: S0016-5107(08)01702-1

doi:10.1016/j.gie.2008.04.020

Gastrointestinal Endoscopy
Volume 68, Issue 5 , Pages 856-858, November 2008

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