Gastroscopy and gastric cancer–related mortality: Time to change recommendations regarding screening?

Abstract

Gastric cancer is the third most common cause of cancer-related death worldwide,1Torre L.A. Bray F. Siegel R.L. et al.Global cancer statistics, 2012.CA Cancer J Clin. 2015; 65: 87-108Crossref PubMed Scopus (23571) Google Scholar and most cases are locally advanced or metastatic at diagnosis. Widespread Helicobacter pylori eradication2Ford A.C. Forman D. Hunt R. et al.Helicobacter pylori eradication for the prevention of gastric neoplasia.Cochrane Database Syst Rev. 2015; : CD005583PubMed Google Scholar and radiologic or endoscopic screening,3Jun J.K. Choi K.S. Lee H.Y. et al.Effectiveness of the Korean national cancer screening program in reducing gastric cancer mortality.Gastroenterology. 2017; 152: 1319-1328.e7Abstract Full Text Full Text PDF PubMed Scopus (238) Google Scholar have been proved to decrease gastric cancer mortality in high-incidence countries. However, in countries with lower incidence, these strategies are probably not cost effective, and there are only recommendations regarding secondary prevention in high-risk patients, such as those with gastric preneoplastic conditions. In fact, the European Society of Gastrointestinal Endoscopy recommends endoscopic surveillance every 3 years in patients with extensive atrophy or intestinal metaplasia (ie, in both corpus and antrum),4Dinis-Ribeiro M. Areia M. de Vries A.C. et al.Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED).Endoscopy. 2012; 44: 74-94Crossref PubMed Scopus (539) Google Scholar and this strategy was found to be cost effective even in a moderate-risk country.5Areia M. Carvalho R. Cadime A.T. et al.Screening for gastric cancer and surveillance of premalignant lesions: a systematic review of cost-effectiveness studies.Helicobacter. 2013; 18: 325-337Crossref PubMed Scopus (92) Google Scholar The American Society for Gastrointestinal Endoscopy recently suggested that surveillance should be offered to patients with gastric intestinal metaplasia who have an increased gastric cancer risk (relevant family history or high-risk ethnic background), with an individualized surveillance interval.6Evans J.A. Chandrasekhara V. et al.ASGE Standards of Practice CommitteeThe role of endoscopy in the management of premalignant and malignant conditions of the stomach.Gastrointest Endosc. 2015; 82: 1-8Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar Although some progress has been made in recent years regarding the management of patients with preneoplastic conditions, a major question remains unsolved: how can we identify the patients who benefit from surveillance? Given that population screening is not an option at this time in low-risk countries, different strategies to identify patients at high risk for gastric neoplasia should be debated and evaluated. Population screening with noninvasive methods such as serum levels of pepsinogen I and II may be an option, although studies using this strategy were mainly performed in high-risk countries.4Dinis-Ribeiro M. Areia M. de Vries A.C. et al.Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED).Endoscopy. 2012; 44: 74-94Crossref PubMed Scopus (539) Google Scholar In most Western countries, therefore, opportunistic screening by upper GI endoscopy with biopsies is probably the best option to identify patients appropriate for surveillance. This could be accomplished through prompt endoscopy in dyspeptic patients, in those with a relevant family history, and possibly in patients undergoing colonoscopy for colorectal cancer screening. In this issue of Gastrointestnal Endoscopy, Leung et al7Leung W.K. Ho H.J. Lin J.T. et al.Prior gastroscopy and mortality in patients with gastric cancer: a matched retrospective cohort study.Gastrointest Endosc. 2018; 87: 119-127Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar present a retrospective nationwide propensity-matched cohort evaluating the impact of gastroscopy on hard outcomes such as gastric-cancer related mortality and overall mortality. They found that gastric cancer patients who had undergone gastroscopy in the 5 years before the diagnosis of gastric cancer fared better in terms of survival than did patients who had never undergone a gastroscopy or whose last gastroscopy was more than 5 years before the diagnosis. Of note, this study included patients with gastroscopies performed by a variety of clinical indications, and patients who underwent screening gastroscopies were not (apparently) included. The survival benefit remained significant even after adjustment for several confounders such as age, comorbidities, and gastric cancer treatments. This is the first study showing a significant survival advantage of recent endoscopy in gastric cancer patients outside of gastric cancer screening programs, and in a region of low to moderate gastric cancer incidence. In fact, the incidence of gastric cancer in Taiwan is 12.7 and 7.0 per 100,000 men and women, respectively—much lower than in other Eastern countries and in some Western regions or settings. As Leung et al7Leung W.K. Ho H.J. Lin J.T. et al.Prior gastroscopy and mortality in patients with gastric cancer: a matched retrospective cohort study.Gastrointest Endosc. 2018; 87: 119-127Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar report, the mechanisms underlying this reduction in mortality could not be fully elucidated and are speculative, but their findings suggest that gastric cancer in patients who have recently undergone endoscopy is detected in earlier stages, allowing those patients to undergo curative treatment. Of note, the time period of this study was before the widespread use of endoscopic resection in early lesions; thus, the benefits of gastroscopy may be even higher in the present time. Moreover, the indications for gastroscopy could not be evaluated, but probably a large proportion of the cohort underwent gastroscopy because of dyspeptic symptoms, preneoplastic conditions (surveillance), or monitoring of gastric ulcer healing. Thus, these findings reinforce the benefit of surveillance in high-risk patients and may also have some implications regarding the initial treatment of dyspeptic patients. The majority of guidelines recommend a noninvasive approach in young patients with dyspepsia without alarming features, with upper GI endoscopy as an alternative. However, endoscopy has the advantage of being the criterion standard for the diagnosis of pathologic conditions in the upper GI tract; thus, a negative examination result may have reassuring effects. Additionally, prompt endoscopy was associated with higher doctor and patient satisfaction, more time without a second endoscopy, and more time without symptoms in comparison with the H pylori test-and-treat strategy or initial therapy with proton pump inhibitors. Despite these advantages, an initial strategy with endoscopy is a more invasive and costly approach, inasmuch as a large proportion of patients will have a normal examination result or minor findings, and its benefits in terms of hard clinical outcomes were not proved. It is also argued by some that prompt endoscopy does not influence management in the majority of patients because most patients will be treated in the same way as those who do not undergo endoscopy (with acid-suppression therapy or H pylori eradication). However, despite premalignant conditions not being considered a major finding, their diagnosis is important because they may influence subsequent management and identify patients at higher gastric cancer risk who may benefit from surveillance with this strategy. In fact, even in low-risk to intermediate-risk areas, approximately 10% to 23% of the general population have gastric preneoplastic conditions, and 10% of the population harbor an extensive phenotype.8Marques-Silva L. Areia M. Elvas L. et al.Prevalence of gastric precancerous conditions: a systematic review and meta-analysis.Eur J Gastroenterol Hepatol. 2014; 26: 378-387Crossref PubMed Scopus (78) Google Scholar These patients for whom surveillance is recommended can be identified by an initial endoscopy performed because of de novo dyspeptic symptoms or at the time of colonoscopy screening for CRC. Although screening upper endoscopy performed at the time of CRC screening colonoscopy was found to exceed the $50,000 per quality-adjusted life year consensus threshold, the cost effectiveness of that strategy was similar to that in other implemented and widely performed preventive programs such as hepatocellular cancer screening in cirrhosis or human papillomavirus vaccination.9Gupta N. Bansal A. Wani S.B. et al.Endoscopy for upper GI cancer screening in the general population: a cost-utility analysis.Gastrointest Endosc. 2011; 74: 610-624.e2Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar Despite this survival benefit in patients with prior gastroscopy, in the study by Leung et al,7Leung W.K. Ho H.J. Lin J.T. et al.Prior gastroscopy and mortality in patients with gastric cancer: a matched retrospective cohort study.Gastrointest Endosc. 2018; 87: 119-127Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar a subset of patients with gastroscopy less than 2 years before the diagnosis of cancer could have a lesion not detected in the prior gastroscopy (missed cancer). Indeed, a recent systematic review found that although a negative EGD result had a very high negative predictive value (99.7%), 9.4% of patients with a gastric cancer diagnosis had recently undergone upper GI endoscopy that had not diagnosed the cancer.10Pimenta-Melo A.R. Monteiro-Soares M. Libanio D. et al.Missing rate for gastric cancer during upper gastrointestinal endoscopy: a systematic review and meta-analysis.Eur J Gastroenterol Hepatol. 2016; 28: 1041-1049Crossref PubMed Scopus (100) Google Scholar This further reinforces the importance of following quality standards in endoscopy. In this regard, several strategies should be used to achieve the aim of detecting gastric preneoplastic conditions and early gastric neoplasms. A careful inspection of the gastric mucosa with special attention to blind areas (such as the cardia and incisura angularis) should be done, although the optimal duration of gastric inspection is yet to be defined. If patient tolerance is poor and optimal inspection is impaired, this should also be reported, and an examination with the patient under sedation should be considered. High-definition endoscopes and virtual chromoendoscopy should also be used whenever possible because they have been found to increase the sensitivity for the detection of intestinal metaplasia and to have a better correlation with the results of histologic analysis, so they can be of benefit in directing biopsies to more suggestive areas. Last, if we aim at identifying patients with premalignant conditions and selecting patients with high-risk phenotype who benefit from surveillance, it is necessary to perform biopsies of both corpus and antrum in 2 separate jars. In summary, Leung et al7Leung W.K. Ho H.J. Lin J.T. et al.Prior gastroscopy and mortality in patients with gastric cancer: a matched retrospective cohort study.Gastrointest Endosc. 2018; 87: 119-127Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar show that patients with gastric cancer with a recent (<5 years) endoscopy have a survival benefit that may be related to the identification and continued surveillance of high-risk patients. The optimal strategy to identify these high-risk patients and the optimal surveillance schedule remain to be elucidated, but given the importance of the identification of patients with a higher risk of gastric cancer, it may be time to consider upper GI endoscopy as the first choice in patients with de novo dyspeptic symptoms. Future studies should evaluate the long-term benefits of prompt upper GI endoscopy in dyspeptic patients and at the time of initial CRC screening. All authors disclosed no financial relationships relevant to this publication. Prior gastroscopy and mortality in patients with gastric cancer: a matched retrospective cohort studyGastrointestinal EndoscopyVol. 87Issue 1PreviewThe role of prior gastroscopy on the outcome of patients with gastric cancer remains unknown. This study determines the association between intervals of prior gastroscopy and mortality in patients with gastric cancer. Full-Text PDF