Comprehensive pathological evaluation of risk factors for metastasis after endoscopic resection of superficial esophageal squamous cell carcinoma

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Abstract
Background Esophageal cancer is a major cause of cancer mortality worldwide. Endoscopic resection (ER) is a curative treatment for esophageal squamous cell carcinoma (ESCC). Predicting risk of metastasis is crucial for post-ER management. In this study, we aimed to identify predictors of metastasis by examining endoscopically resected specimens. Methods The cohort of this retrospective multicenter study comprised 422 patients who had undergone ER for ESCC from 1994 to 2017. Inclusion required a histological diagnosis of pT1a-muscularis mucosa or pT1b-submucosa (SM) cancer. Central pathological review comprehensively evaluated depth of invasion, lymphovascular invasion (LVI), droplet infiltration (DI), infiltrative growth pattern, histological differentiation, intraductal and intraglandular involvement, solitary nest, resected margin, and other factors. Logistic regression was used to identify predictors of metastasis. Results Metastases were identified in 103 patients. Univariate analysis identified LVI, depth of invasion, and DI as significant predictive factors. Multivariate analysis identified LVI, depth of invasion pT1b-SM2 (odds ratio 2.72) and indeterminate (positive vertical margin) (odds ratio 3.63) compared with the reference category of pT1b-SM1 as independent predictors of metastasis. Conversely, there were no significant associations between metastasis and lesion size, differentiation, cytological atypia, or infiltration pattern. Subgroup analysis showed that both the number and layer of LVI were associated with metastasis risk. In addition, four or more foci of DI was an independent predictor of LVI. Conclusions LVI and depth of invasion were significant predictors of metastasis in ESCC. Detailed pathological evaluation and standardized criteria are essential for accurately assessing risk of metastasis and guiding post-ER treatment strategies.

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