Effcacy of Endoscopic Screening for Esophageal Cancer in China (ESECC): a Population-based Randomized Controlled Trial

BACKGROUND Esophageal cancer (EC) is one of the most common cancers in the world, and is a leading cause of cancer death, with more than 450,000 new cases and 400,000 deaths in 2012.Nearly half of the new cases of EC worldwide are found in China, and esophageal squamous cell carcinoma (ESCC) is the predominant histologic type. A series of etiologic factors for ESCC have been proposed in previous studies conducted in high prevalence regions of China, including age, family history of ESCC, poor nutritional status, smoking and drinking, chemical carcinogen exposure, and human papillomavirus (HPV) infection. But the main etiologic factors have not been definitively identified.

Because there are typically no symptoms in the early stages of ESCC, the vast majority of cases are clinically diagnosed at an advanced stage. The overall five-year survival is about 20% in China, and is even lower in less developed countries. However, if the disease is found at an early stage, the five-year survival may be 80% or greater. This profound improvement in survival indicates there is clearly a need for effective early detection strategies to enable earlier diagnosis and curative treatment. Esophageal squamous dysplasia (ESD) is considered to be the premalignant precursor lesion for ESCC, and harbors a high risk for progression into invasive cancer. ESD as well as early-stage malignant lesions (carcinoma in situ, CIS) are therefore screening targets for ESCC. Various screening methods have been tested, and endoscopy with iodine staining is the gold standard technique for the diagnosis of ESCC and its precursor lesions. Endoscopic screening has therefore been widely accepted as an optimal strategy in the secondary prevention of ESCC. However, taking the high cost and invasive nature of endoscopy into consideration, the efficacy and cost-effectiveness of such screening, must be evaluated prior to introduction of a population-wide screening program. Evidence regarding the efficacy of endoscopic screening for ESCC has been based predominantly on observational studies in high risk regions. There has been only one non-randomized controlled trial which reported that endoscopy plays a positive role in reducing mortality. No randomized controlled trials (RCTs) evaluating endoscopic screening have been reported to date. Observational studies and trials which are not randomized are limited in determining the true benefits of screening on reducing mortality due to potential lead-time bias, length-time bias and confounding bias. Hence, one-step large-scale population-based RCT are needed to determine the efficacy of endoscopic screening for ESCC.

In January 2012, we initiated the ESECC (Endoscopic Screening for Esophageal Cancer in China) trial in rural Hua County of Henan Province, which is a high-risk region in northern central China. This is the first population-based RCT aiming to evaluate the efficacy and cost-effectiveness of endoscopic screening for ESCC worldwide.

STUDY DESIGN Setting and participants This ESECC trial was undertaken in rural Hua County, which is an agricultural region in the northern part of Henan Province, Peoples Republic of China with a rural population of 1.1 million. The mortality for ESCC in this area is among the highest in the world.

Participants were eligible for the study if they meet the following criteria: 1) permanent residency in a target village; 2) age 45-69 (>5 years of life expectancy), and no history of endoscopic examination within 5 years prior to the initial interview; 3) no history of cancer or mental disorder; 4) negative for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV); 5) voluntary participation and agreement to complete all phases of the examination.