Esophageal cAncer Screening Trial
Condition: Esophageal Squamous Cell Carcinoma; Esophageal Cancer; Gastroesophageal Junction Adenocarcinoma
MeSH terms: Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma
Study type: Observational

Summary: 
      This multicenter study aims to include 15000 participants undergoing screening upper
      gastrointestinal endoscopy and establish a risk prediction model for esophageal squamous cell
      carcinoma and esophagogastric junctional (EGJ) adenocarcinoma in high-risk areas. The
      prediction model will be built based on epidemiological and cytological features, acquired
      from the esophageal sponge cytology test. The primary study outcome is the diagnostic
      performance of the model to detect high-grade lesions (including carcinoma and high-grade
      intraepithelial neoplasia) of the esophagus and EGJ. Secondary outcomes include the number
      needed to screen, and dignostic performance of cytologist under AI assistance and abnornal
      cell count.
    

Detailed description: 
      Esophageal cancer is the seventh most common cancer and the sixth leading cause of cancer
      related death worldwide in 2020. The highest-incidence areas include Eastern and Central
      Asia, sub-Saharan Africa, and some South American countries, with esophageal squamous cell
      carcinoma (ESCC) being the dominant histologic subtype (nearly 90%). While esophageal
      adenocarcinoma, as a type of adenocarcinoma of the esophagogastric junction (AEG), was less
      common in these high-risk areas, but accounts for approximately two-thirds of esophageal
      cancer cases in Europe and North America. However, cardiac gastric cancer, another type of
      AEG, often shows high incidence in ESCC high-risk areas. Strikingly, 57.5% of global ESCC
      cases and 60.8% of cardiac gastric cancer cases were estimated to occur in China in 2018.
      Most esophageal cancer high-risk areas locate in developing countries with limited medical
      resources, high incidence and co-occurrence ESCC and AEG have posed significant challenges
      for disease control.

      Both ESCC and AEG demonstrate dismal prognosis, with an overall 5-year survival of less than
      30%. This is largely due to the asymptomatic nature of early-stage lesions, which frequently
      leads to delayed diagnosis. Population-based studies in China have confirmed that upper
      gastrointestinal endoscopy with Lugol's staining could increase the early detection rate and
      decrease both the incidence and mortality of ESCC and the mortality of AEG in very high-risk
      areas. However, the invasiveness and resource intensiveness of endoscopic procedure and
      relative low prevalence of target lesions in the general screening population (0.8% to 1.6%)
      limit its feasibility and cost-effectiveness in massive screening. Therefore, developing less
      invasive, readily accessible methods with acceptable diagnostic accuracy is urgently needed
      for enrichment of high-risk individuals prior to endoscopy. To date, few non-endoscopic
      preliminary screening methods were available for ESCC and AEG.

      The esophageal sponge cytology is an emerging, minimally invasive, and convenient test for
      esophageal cancer as well as its precancerous lesions and conditions. The expandable sponge
      could harvest epithelial cells from the entire esophagus and the esophagogastric junction
      (EGJ) during withdrawn, and subsequent morphological or biomarker analysis could be
      performed. For Barrett esophagus (BE), the Cytosponge-trefoil factor 3 is a well-established
      non-endoscopic test, and could increase the detection of BE for 10.6-fold among patients with
      reflux symptoms in the primary care setting. For high-risk areas, where ESCC is the dominant
      subtype, several types of sponge cytology tests also gained promising yet preliminary
      results.

      In our previous study, we have developed an artificial intelligence (AI)-assisted sponge
      cytology test, which automatically indicated potentially abnormal cells for cytologist
      diagnosis, and found the sensitivity and specificity to be 90.0% and 93.7% in community-based
      ESCC screening in China. However, the inadequacy of experienced cytologists makes this method
      still suboptimal for population-based screening, especially for resource-limited areas.
      Furthermore, AEG, which is also within the detection range of the sponge cytology, has not
      been investigated in previous studies. Therefore, we conducted the Esophageal cAncer
      Screening Trial (EAST) to develop and validate a fully-automated machine learning model based
      on cytological and epidemiological features for ESCC and AEG screening in high-risk areas.
    

Intervention name(s): Sponge cytological test
Intervention type(s): Diagnostic Test
Intervention description(s): Esophageal cell specimen were collected with Esoheal 1.0 sponge collection device. A prediction model will be built based on digital cytopathological features of participants.
Observational model: Other
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        This study enrolled participants undergoing endoscopic opportunistic screening for
        esophageal cancer, after excluding participants with alarming symptoms, known history of
        esophageal neoplasia, previous upper endoscopy within one year, and conditions that are not
        suitable for endoscopy and biopsy.
      
Biospecimen description: 
      1. Esophageal cell specimen collected with novel sponge cell collection device;

        2. Esophageal formalin-fixed paraffin-embedding tissue sample collected with endoscopic
           biopsy.
    
Keywords: Esophageal Cancer; Screening and Early Detection; Sponge Cytology; Risk Stratification