Advances in diagnosis and management of cancer of the esophagus

Correspondence to N Deboever, [email protected], [email protected]

Introduction

Esophageal cancer is a significant global health challenge, being the seventh most common malignancy worldwide with over 470 000 new cases each year. Esophageal cancer primarily manifests in two histological subtypes: esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), which are biologically distinct. Despite advancements, outcomes for esophageal cancer remain poor, primarily owing to late stage diagnosis in most patients. However, emerging strategies aimed at the early detection of precursor lesions such as squamous dysplasia and Barrett’s esophagus hold promise for improving these outcomes. The treatment landscape for esophageal cancer is evolving, with the introduction of biologic agents and immune checkpoint inhibitors enhancing systemic treatment for locally advanced and metastatic cases. Additionally, advancements in minimally invasive surgical and endoscopic techniques, along with precision radiotherapy technologies, further contribute to improved patient prognosis. This comprehensive review explores the current state-of-the-art diagnostic and treatment approaches for esophageal cancer, highlighting recent progress in understanding the disease’s biology and the implications for clinical practice.

Epidemiology

Together, EAC and ESCC impose a considerable healthcare burden; accounting for the annual loss of more than 400 000 lives and 9.8 million disease adjusted life years.³⁴ These figures reflect a 52% increase in the total number of new cases and a 40% rise in the total number of deaths between 1990 and 2017, even as the age standardized incidence and mortality fell by 22% and 29%, respectively.³

Around 90% of worldwide cases are ESCC, which has particularly high incidence in South America and the Asian esophageal cancer belt that extends from East Africa and sub-Saharan Africa through much of Central Asia.³⁵⁶ EAC is, by contrast, more prevalent in Europe and high income North America, where its incidence has increased fourfold over the past four decades.³⁷

These trends are reflected by the different epidemiological associations of the two subtypes. ESCC is linked with alcohol, tobacco and opium use, environmental pollution, ingestion of high temperature beverages, nutritional deficiencies, and other dietary factors such as consumption of pickled foods and high nitrosamine exposure.⁵⁸ In rare cases, human papillomavirus has also been linked to ESCC development, although data remain uncertain.⁹¹⁰ By contrast, EAC associates with obesity, the...