Non-endoscopic Esophageal Cancer Screening Program in Northern Iran

Background:

Esophageal cancer (EC) is the 8th most common cancer and the 6th most common cause of death from cancer worldwide. Golestan province located in Northern Iran has been known as a high-risk area for esophageal squamous cell carcinoma (ESCC). Recent reports suggest an increasing rate of esophageal adenocarcinoma (EAC) in this region as well. Designing and implementing of screening programs may be effective for controlling these cancers. The investigators aim to develop a screening program for esophageal cancer in this region. The pilot phase of this project, the Golestan EC Screening Program (GESP), was conducted during 2011 and 2012 among 300 asymptomatic participants of Golestan Cohort Study (GCS), which is a prospective population-based cohort of 50,045 individuals, aged 40-75 years at baseline, in the eastern half of Golestan Province, Iran. The initial results of the GESP project showed a low participation rate for endoscopic screening. In other words, endoscopic ESCC screening was not feasible in our population, suggesting the need for a non-endoscopic screening method. Further results of the GESP project suggested that capsule sponge cytology is a feasible and valid primary method for ESCC screening in this region. Because of the promising findings of the GESP project, it has been decided to start the main phase of the EC screening program, called the "Non-endoscopic EC Screening Program in Northern Iran (NESP)". The aim of this study is to assess the effects of implementation of a non-endoscopic EC screening program on outcomes of interest in an asymptomatic high-risk population in Golestan Province, Iran.

Methods:

For sample size calculations, the investigators considered different scenarios based on the published literature and unpublished data. The prevalence of high grade dysplasia in the general population of Golestan has been estimated to be 1.4-3.6%. The sensitivity of cytological detection of esophageal squamous dysplasia (ESD) was predicted to be about 46% based on studies from China, and 60-100% based on studies from Iran, and according to previous studies, 27-65% of ESD lesions progress to invasive ESCC without treatment. The investigators used a rather conservative assumption to calculate sample size: a dysplasia prevalence of 1.5%, a 60% sensitivity for the sponge cytology, and a 2% progression to invasive ESCC in the screened (and treated) group vs. 40% in the untreated group. The investigators also assumed a power of 90%, a mean cluster size of 28 based on the PolyIran study (CV=0.84%), and an intra-class correlation (ICC) of 0.01. Based on these assumptions the investigators will need 4980 people in each arm. So, the investigators need to enroll 9,960 GCS participants > 50 years old. Estimating a 20% lack of consent, the final invitation lists of NESP project will consist of 12000 GCS participants including 6000 subjects in the intervention (capsule sponge) arm and 6000 subjects in the control arm.

A list of 12000 subjects from GCS participants will be prepared. Sampling will be done using a cluster randomization method. Each village will be considered as a cluster. Clusters will randomly be allocated into two groups, the intervention group (group 1) and the control group (group 2). Capsule sponge examination will be performed for all subjects in intervention clusters. But, participants in control clusters will be enrolled without capsule sponge examination. Both intervention and control subjects will be offered endoscopy if they develop upper GI symptoms according to current clinical practice.