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. ABSTRACT: 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.