Gastric cancer prevention: Bridging data, ethics and microsimulation

Gastric cancer is a highly fatal disease causing around 650,000 deaths each year. Because most of these cases are attributable to the bacterium Helicobacter pylori (H. pylori), gastric cancer can be prevented by antibiotic treatment of the infection. Additionally, endoscopic screening can enable earlier diagnosis and improve survival. The effectiveness of these interventions may be further enhanced by targeting populations with an elevated risk, such as specific ethnic or social groups. While both of these strategies offer viable options to reduce the burden of gastric cancer, they only prevent gastric cancer in relatively few individuals while they carry important harms for the entire population undergoing screening, such as false-positive test results, overtreatment and costs. The challenge is to find strategies that balance the benefits and harms of screening. This thesis therefore aims to answer the central question:

How to best prevent the burden of gastric cancer?

This thesis aims to use data, ethics and microsimulation to find the answer. The thesis starts by investigating gastric carcinogenesis through analyzing endoscopic data on gastric cancer precursor lesions. These data are subsequently used in the development of the MISCAN-gastric model, a microsimulation model to estimate the impact of prevention strategies. The model is used alongside other models and data sources to investigate the balance between harms and benefits of prevention strategies in Europe, Asia and the United States. Finally, the thesis provides a broader perspective related to recent updates in guidelines, the effects of H. pylori screen-and-treat beyond gastric cancer and ethics.

Although gastric cancer has long been neglected in global cancer control efforts, the work presented in this thesis suggests reason for optimism. With the thoughtful application of existing technologies – such as H. pylori screen-and-treat and endoscopic screening – there is potential to make meaningful progress in reducing the burden of gastric cancer. Encouragingly, the global landscape of GC prevention is beginning to shift, as reflected in the development of new guidelines and the implementation of prevention programs in several countries. Rather than waiting for future breakthroughs, actionable opportunities already exist: the challenge now lies in applying current tools wisely.