Strategies on endoscopic screening for esophageal cancer at early stage and high-risk subjects with esophageal precancerous lesions on symptom-free subjects in high-incidence areas

Esophageal squamous cell carcinoma (ESCC) remains a major cause of cancer-related mortality in high-incidence areas such as Linzhou and Anyang cities in Henan Province, China. Despite the high survival rate of early-stage ESCC post-surgery, over 90% of patients are diagnosed at advanced stages due to the lack of specific early symptoms. This necessitates effective screening strategies for high-risk subjects (HRS) who are symptom-free in these high-incidence areas (HIA). Endoscopic biopsy and histopathological examination are critical methods for identifying ESCC in symptom-free subjects (SFS) within these regions.

Limitations of Endoscopy in Screening 

Endoscopy, combined with iodine staining and targeted mucosal biopsy, is considered an effective method for detecting early ESCC. Generally, symptom-free residents over 35 years of age in HIA are the most suitable for HRS screening. Despite its effectiveness in identifying early ESCC and precancerous lesions, endoscopy has significant limitations for large-scale application. The procedure is invasive, costly, and requires experienced endoscopists and specific equipment. The standard endoscopic procedure, including iodine staining and biopsy, takes 30-60 minutes per patient, limiting the number of individuals that can be screened daily. Furthermore, almost 90% of the screened individuals show normal esophageal epithelia, leading to overexamination and resource wastage. Thus, improving the efficiency of endoscopy by enhancing disinfection processes and reducing procedure time is crucial but challenging.

Serological Screening and Two-step Approach 

To address these limitations, a two-step screening method is proposed. The first step involves non-invasive serological screening to detect neoplasm-related molecules in the blood, which reflect esophageal epithelial lesions. Only individuals with high-risk indicators proceed to the second step: endoscopic and histopathological examinations. This approach can significantly reduce costs and improve the effectiveness of large-scale screenings. By detecting molecular markers related to the progression of ESCC in peripheral blood and combining these with data profiles of family history and living habits, the risk of subjects can be classified into mild, moderate, and severe categories. Only severe risk patients would require endoscopic examination. This combination approach could significantly reduce the extent of endoscopic examinations and screening costs while improving the detection rate of HRS.

Serum Tumor-associated Markers and Liquid Biopsy 

Advancements in molecular biology have identified several serum markers that are promising for ESCC screening. Tumor-associated autoantibodies, circulating microRNAs, and circulating tumor DNA (ctDNA) are notable examples. These markers offer a non-invasive, high-throughput, and cost-effective screening option. Tumor-associated autoantibodies, produced in response to mutations, overexpression, or abnormal processing by humoral immune response throughout tumorigenesis, have shown high specificity but variable sensitivity for ESCC. Panels of autoantibodies have increased sensitivity and specificity for ESCC detection. Circulating microRNAs, small non-coding RNAs of approximately 20-25 nucleotides in length, are stable and relatively cheap to assay, making them beneficial for distinguishing early-stage ESCC patients from healthy controls. High levels of methylated ctDNA, associated with poor prognosis in ESCC, can distinguish esophageal cancer patients from benign and healthy controls with high sensitivity and specificity.

Challenges and Future Directions 

Despite the promise of serum markers, their sensitivity and specificity need further improvement and validation in large population studies. Combining multiple serum markers may be an effective method to enhance accuracy. Furthermore, developing an accurate and effective serological screening test requires evaluating these markers in high-risk populations to determine their true application value. The successful implementation of the two-step screening method also requires government support to ensure cost-effectiveness and population compliance, especially in rural areas. Government leadership plays a decisive role in ensuring the implementation of this screening method, as the cost of testing and population compliance must be guaranteed.

Conclusions 

The integration of serological screening with endoscopic examination offers a promising strategy for early ESCC detection in high-incidence areas. Continued research and validation of serum markers, along with government support, are essential for the successful implementation of this two-step screening method. This approach can enhance early detection, reduce costs, and ultimately improve outcomes for high-risk populations. In summary, the development of liquid biopsy is the key basis for the two-step method and its successful application. Exploring suitable examination costs and logistical systems is essential to make the two-step screening available within the current rural (community) new cooperative medical system.

Full text

https://www.xiahepublishing.com/2835-3315/CSP-2023-00008

The study was recently published in the Cancer Screening and Prevention.

Cancer Screening and Prevention (CSP) publishes high-quality research and review articles related to cancer screening and prevention. It aims to provide a platform for studies that develop innovative and creative strategies and precise models for screening, early detection, and prevention of various cancers. Studies on the integration of precision cancer prevention multiomics where cancer screening, early detection and prevention regimens can precisely reflect the risk of cancer from dissected genomic and environmental parameters are particularly welcome.

Follow us on X: @xiahepublishing

Follow us on LinkedIn:  Xia & He Publishing Inc.