Changing trends in gastric cancer incidence and mortality: the role of upper endoscopy in low-risk countries

Gastric cancer, which is diagnosed in approximately one million new patients annually, is a significant contributor to global cancer burden and cancer-related mortality [1]. East Asia, eastern Europe, and Latin America have the highest incidences, while North America and most of western Europe have relatively low incidences [2]. This geographical variation is thought to be associated with several different predisposing and etiologic factors among the countries, such as tumor biology, Helicobacter pylori (H. pylori) infection rate, cigarette smoking, and a high sodium diet with salt-preserved foods. Global age-standardized gastric cancer incidence has steadily declined over the past century, particularly in high-risk countries such as Korea and Japan. This trend has been linked to a decline in noncardia cancer because of the eradication of H. pylori [2]. Contrarily, in countries with low gastric cancer incidence, such as those in western Europe and the USA, the decline in gastric cancer has reduced, especially in the middle-aged population [1] [2]. This phenomenon may also be related to changes in H. pylori infection patterns or the increased proportion of cardia cancer related to epidemic obesity and gastroesophageal reflux disease [1]. As with incidence, global gastric cancer mortality has also decreased [2]. Improvements in surgical techniques and the development of chemotherapy regimens have led to better survival outcomes. Above all, early detection of cancer is a crucial factor contributing to the decline in mortality.

“Further large-scale cohort studies to determine high-risk groups in low-incidence areas should be conducted, and efforts to ensure high-quality endoscopy through updates, training, and expansion of standard protocols should be continued.”

The current issue of Endoscopy includes two large cohort studies using European population-based data. The first study, by Libânio et al., investigated gastric cancer incidence and mortality from 2007 to 2016 in populations of northwestern and southern European countries and compared their trend over 5-year periods [3]. Data from 41,138 cases indicated a downward trend in gastric cancer incidence and mortality, consistent with global trends. However, as observed in some western countries, the authors found that the decline in incidence had gradually plateaued. As mentioned, this may be due to the low impact of eradication of H. pylori and the increasing proportion of cardia cancer. In this regard, a paradigm shift regarding gastric cancer prevalence and a new approach for high-risk patients may be needed, especially in low-risk countries.

This study further found that T1 cancer incidence steadily increased and the net survival significantly improved after 2012, when the European guidelines on the management of epithelial precancerous conditions and lesions in the stomach (MAPS) were presented. The increased number of endoscopies performed according to the guidelines may have led to the early detection of cancer and contributed to the decline in mortality. This aspect has been studied through screening-related data analysis, mainly in Korea and Japan, where national screening programs have been implemented. A nested case–control study using large-scale cohort data from the National Cancer Screening Program for gastric cancer (n = 54 418) in Korea showed a statistically significant dose–response relationship between endoscopic gastric cancer screening and gastric cancer-related mortality [4]. However, implementation of a nationwide screening program in Europe may not be as cost effective, as the incidence of gastric cancer is low. To maximize the benefits of the screening program, an optimal strategy, such as targeting endoscopy to a population group based on risk stratification, is required. The recently published MAPS II guideline update 2019 includes detailed criteria for surveillance targeting [5]. However, in the future, it will be essential to provide guidelines not only for surveillance targets but also for appropriate screening targets.

The effectiveness of screening programs is also influenced by the quality of endoscopy. Even within an organized screening program, the effectiveness of screening is bound to decrease if the cancer miss rate is high. Greater endoscopy experience and skills are required to prevent missed cancers, particularly in high-risk and surveillance populations. Therefore, high-quality endoscopy with a reduced cancer miss rate is essential for optimizing the effectiveness, and cost-effectiveness, of a screening program.

The second European population-based cohort study in this issue is by Januszewicz et al., who reported the miss rate of upper gastrointestinal cancer and analyzed its risk factors based on two Polish cohort datasets [6]. While most of the previous studies have had small sample sizes and limited meta-analysis due to significant heterogeneity, this study included large-scale cohort data (4 105 399 patients) and analyzed multifactorial risk factors for missed cancers. Similarly to previous Western studies, this study showed a 6 % miss rate, which was fairly stable over time despite the number of endoscopies being performed increasing over time.

The previously reported risk factors of missed cancers were patient compliance, disease characteristics, and endoscopic quality such as the instrument used or the endoscopist’s experience or skill. Notably, this study revealed that the primary care endoscopy units with low annual endoscopy volume had a significantly higher miss rate than secondary care units. As mentioned by the authors, this may be due to the differences in endoscopy quality between the two care sectors. These results suggest that endoscopy quality control is an important issue that can improve miss rates.

The quality indicators of endoscopy can be evaluated using the following three components: the quality of the organizational structure, healthcare processes, and clinical outcomes. Among them, the effectiveness of the screening program can be assessed primarily by the indicators of clinical outcomes. However, in contrast to colonoscopy, the development of such quality indicators is difficult in upper endoscopy because of the relatively low incidence of upper gastrointestinal cancer and the difficulty of long-term follow-up. Therefore, quality indicators have mainly focused on the first two aspects. Nonetheless, some protocols for performance indicators of upper endoscopy have been proposed in order to reduce variations between individual endoscopists and units; such procedure standards include observation time, biopsy protocol, and disease-specific techniques [7]. This attempt at standardization is essential for improving the quality of diagnostic upper endoscopy.

In conclusion, both primary and secondary prevention are important to reduce gastric cancer incidence and mortality, and secondary prevention is a more relevant issue in Western countries where gastric cancer risk is relatively low. In the future, the selection of high-risk groups and application of high-quality endoscopy may be needed. Further large-scale cohort studies to determine high-risk groups in low-incidence areas should be conducted, and efforts to ensure high-quality endoscopy through updates, training, and expansion of standard protocols should be continued.

Publication History

Article published online:
25 February 2022

• References

• 1 Luo G, Zhang Y, Guo P. et al. Global patterns and trends in stomach cancer incidence: age, period and birth cohort analysis. Int J Cancer 2017; 141: 1333-1344
• 2 GBD 2017 Stomach Cancer Collaborators. The global, regional, and national burden of stomach cancer in 195 countries, 1990–2017: a systematic analysis for the Global Burden of Disease study 2017. Lancet Gastroenterol Hepatol 2020; 5: 42-54
• 3 Libânio D, Rodrigues JR, Bento MJ. et al. Gastric cancer incidence and mortality trends 2007–2016 in three European countries. Endoscopy 2022; 54: 644-652 DOI: 10.1055/a-1673-1118.
• 4 Jun JK, Choi KS, Lee HY. et al. Effectiveness of the Korean National Cancer Screening Program in reducing gastric cancer mortality. Gastroenterology 2017; 152: 1319-1328
• 5 Pimentel-Nunes P, Libânio D, Marcos-Pinto R. et al. Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG), European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019. Endoscopy 2019; 51: 365-388
• 6 Januszewicz W, Witczak K, Wieszczy P. et al. Prevalence and risk factors of upper gastrointestinal cancers missed during endoscopy: a nationwide registry-based study. Endoscopy 2022; 54: 653-660 DOI: 10.1055/a-1675-4136.
• 7 Beg S, Ragunath K, Wyman A. et al. Quality standards in upper gastrointestinal endoscopy: a position statement of the British Society of Gastroenterology (BSG) and Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS). Gut 2017; 66: 1886-1899