Risk factors for metachronous esophageal squamous cell carcinoma after endoscopic or surgical resection of esophageal carcinoma: a systematic review and meta-analysis

BACKGROUND: early-stage esophageal carcinoma (EC) patients lack typical clinical signs and symptoms and are often diagnosed and treated at a late stage, leading to a poor prognosis and a high incidence of metachronous esophageal squamous cell carcinoma (MESCC) and second primary carcinoma (SPC). The aims of the review were to identify and quantify risk factors for MESCC and analysis location of SPC in postoperative patients with EC; to predict incidence of MESCC over follow-up time. METHODS: an electronic search of studies reporting potential risk factors, the incidence of MESCC, and the location of SPC were performed on PubMed, Web of Science, Cochrane Library, Embase, and Scopus from inception to 10 November 2022. The Newcastle-Ottawa scale was used to assess the study quality, and the qualitative strength of evidence rating of all items was provided. The meta-regression model was used to predict the incidence of MESCC over follow-up time, the location distribution of SPC was presented using clustered column chart, while the publication bias was assessed using funnel plots and Egger’s test. RESULTS: smoking, age, history of multiple other cancer, and Lugol-voiding lesions (LVLs) were determined to be the risk factors of MESCC. LVLs were qualitatively determined as “definite” and the history of multiple other cancer as “likely.” The overall pooled MESCC incidence was 20.3% (95% CI: 13.8% to 26.8%), with an increase of 0.20% for each additional year of follow-up. The head and neck were the most common locations for SPC, followed by the esophagus. CONCLUSION: timely investigating the age of patients, previous history of cancer and monitoring the number of LVLs in the first 5 years after operation are of great significance to identify high-risk populations of MESCC for timely medical care. Education and behavior correction about smoking are advocated. Tumor markers should be regularly detected in the head and neck, esophagus, and stomach. Endoscopic resection was associated with a higher incidence of MESCC, which provided a reference for doctors to choose the removal method. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022377030.