Impact of Perineural Invasion and Preexisting Type 2 Diabetes on Patients with Esophageal Squamous Cell Carcinoma Receiving Neoadjuvant Chemoradiotherapy

Simple Summary Neoadjuvant chemoradiotherapy followed by surgery is the standard treatment in locally advanced esophageal squamous cell carcinoma. This multimodality strategy provides survival benefits superior to surgery alone, especially in patients obtaining a pathological complete response (pCR). Owing to subsequent recurrence and metastasis, many patients do not achieve a pCR (non-pCR) after neoadjuvant chemoradiotherapy and therefore have very poor outcomes. It is necessary to identify poor prognostic factors. In this real-world data analysis and retrospective cohort study, we found that the presence of perineural invasion and preexisting type 2 diabetes had negative impacts on disease-free survival in the non-pCR population. Patients with a combination of both two factors had the worst survival. Our findings provide clinical information for future translational investigations and possible clinical applications. Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the cornerstone treatment strategy in locally advanced esophageal squamous cell carcinoma (ESCC). Despite this high- intensity multimodality therapy, most patients still experience recurrences and metastases, especially those who do not achieve a pathological complete response (pCR) after neoCRT. Here, we focused on identifying poor prognostic factors. In this retrospective cohort study; we enrolled 140 patients who completed neoCRT plus surgery treatment sequence with no interval metastasis. Overall, 45 of 140 patients (32.1%) achieved a pCR. The overall survival, disease-free survival (DFS), and metastasis-free survival was significantly better in patients with a pCR than in patients with a non-pCR. In the non-pCR subgroup, the presence of perineural invasion (PNI) and preexisting type 2 diabetes (T2DM) were two factors adversely affecting DFS. After adjusting for other factors, multivariate analysis showed that the hazard ratio (HR) was 2.354 (95% confidence interval [CI] 1.240-4.467, p = 0.009) for the presence of PNI and 2.368 (95% CI 1.351-4.150, p = 0.003) for preexisting T2DM. Patients with a combination of both factors had the worst survival. In conclusion, PNI and preexisting T2DM may adversely affect the prognosis of patients with ESCC receiving neoadjuvant chemoradiotherapy.