Trimodal Therapy in Esophageal Squamous Cell Carcinoma: Role of Adjuvant Therapy Following Neoadjuvant Chemoradiation and Surgery

SIMPLE SUMMARY: In this work, we aimed to explore the effectiveness of adjuvant therapy after trimodal therapy (neoadjuvant chemoradiotherapy and esophagectomy) in patients with thoracic esophageal squamous cell carcinoma (ESCC). Overall survival (OS) and disease-free survival (DFS) were both compared for adjuvant and non-adjuvant groups. Propensity score matching was used to eliminate the confounding factors between the two groups. Meanwhile, subgroup analysis based on a neoadjuvant-treated node stage (ypN) was performed to precisely stratify the patients and to guide the clinical decision-making at the point of care. As of now, there is no guideline or recommendation on the treatment of ESCC patients with adjuvant therapy after neoadjuvant chemoradiotherapy followed by surgery. The results of our study indicate that adjuvant therapy after trimodal therapy could shorten OS and DFS in patients with ESCC. Meanwhile, adjuvant therapy is an independently unfavorably prognostic factor for DFS. Therefore, adjuvant therapy is not recommended for ESCC patients after trimodal therapy, especially patients without nodal metastases after neoadjuvant therapy. To our knowledge, this is the first retrospective study using subgroup analysis to examine the effect of adjuvant therapy in ESCC patients after trimodal therapy by comparing overall survival and disease-free survival. The results of our study add useful evidence to recent guidelines. ABSTRACT: Background: The aim of this study was to determine the role of adjuvant therapy after neoadjuvant chemoradiotherapy and esophagectomy for esophageal squamous cell carcinoma (ESCC). Methods: The study retrospectively reviewed 447 ESCC patients who underwent neoadjuvant chemoradiotherapy and esophagectomy. Patients were divided into an adjuvant therapy group and no adjuvant therapy group. Propensity score matching was used to adjust the confounding factors. Results: 447 patients with clinical positive lymph nodes and no distant metastasis treated with neoadjuvant chemoradiotherapy and esophagectomy were eligible for analysis. After propensity score matching, there were 120 patients remaining in each group. Patients receiving adjuvant therapy had a significantly shorter post-resection overall survival (OS) and disease-free survival (DFS) when compared to patients not receiving adjuvant therapy (log-rank, OS: p = 0.046, DFS: p < 0.001). Receiving adjuvant therapy is not an independently prognostic factor for OS (hazard ratio (HR): 1.270, HR: 0.846–1.906, p = 0.249) but a significantly unfavorable independent prognostic factor for DFS (HR: 2.061, HR: 1.436–2.958, p < 0.001). Conclusions: The results of our study indicate that adjuvant therapy after neoadjuvant chemoradiotherapy and surgery could reduce the OS and DFS in patients with ESCC. Therefore, adjuvant therapy is not recommended for ESCC patients after neoadjuvant chemoradiotherapy and esophagectomy, especially patients without nodal metastases after neoadjuvant therapy.