Current Status and Future Prospects for Esophageal Cancer

SIMPLE SUMMARY: Over 500,000 individuals died due to esophageal cancer (EC) worldwide in 2020. More than four decades of etiological research have predominantly focused on the esophageal squamous cell carcinoma (ESCC) subtype, which accounts for 80% of EC cases, while less etiologic research has been done on the esophageal adenocarcinoma (EAC) subtype whose incidence rates are rapidly increasing in some high-income countries. Recent advances in genomics and microbiome studies, and the establishment of high-quality research infrastructure in high-risk regions, including Africa and Iran, have advanced our understanding of the causes and potential risk factors of these diseases in different regions. For therapy and early detection, topical studies that have used chemoprevention methods, such as using aspirin and proton pump inhibitors, and early detection methods, such as using Cytosponge™ and biomarker assays among symptomatic or high-risk individuals, have shown promising results. However, there are still challenges in each field that need to be addressed in future studies. ABSTRACT: Esophageal cancer (EC) is the ninth most common cancer and the sixth leading cause of cancer deaths worldwide. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two main histological subtypes with distinct epidemiological and clinical features. While the global incidence of ESCC is declining, the incidence of EAC is increasing in many countries. Decades of epidemiologic research have identified distinct environmental exposures for ESCC and EAC subtypes. Recent advances in understanding the genomic aspects of EC have advanced our understanding of EC causes and led to using specific genomic alterations in EC tumors as biomarkers for early diagnosis, treatment, and prognosis of this cancer. Nevertheless, the prognosis of EC is still poor, with a five-year survival rate of less than 20%. Currently, there are significant challenges for early detection and secondary prevention for both ESCC and EAC subtypes, but Cytosponge™ is shifting this position for EAC. Primary prevention remains the preferred strategy for reducing the global burden of EC. In this review, we will summarize recent advances, current status, and future prospects of the studies related to epidemiology, time trends, environmental risk factors, prevention, early diagnosis, and treatment for both EC subtypes.