The feasibility and safety of radical esophagectomy in patients receiving neoadjuvant chemoradiotherapy with pembrolizumab for esophageal squamous cell carcinoma

Background: Immune checkpoint inhibitors have been tried for several thoracic malignancies; however, their application as a neoadjuvant therapy in esophageal squamous cell carcinoma (ESCC) has not been studied. We evaluated the feasibility and safety of esophagectomy and total lymphadenectomy after neoadjuvant chemoradiation therapy with pembrolizumab. Methods: Between 2017 and 2018, 38 patients who received the neoadjuvant therapy followed by radical esophagectomy and total lymphadenectomy for ESCC were analyzed. Twenty-two patients received conventional neoadjuvant chemoradiation therapy (Group 1), and sixteen patients received neoadjuvant chemoradiation therapy with pembrolizumab in clinical trial (Group 2). Two groups were compared retrospectively. Results: The basic characteristics of age, clinical stage, location and methods of operation were not different between the two groups. The pathologic stages were higher in Group 2, but the difference was not statistically significant. The operative outcomes, i.e., operation time, blood loss, and numbers of dissected lymph nodes in the thorax, neck, and abdomen were comparable. Complications, including pulmonary complications and anastomotic leakage, were also comparable. The rate of recurrent laryngeal nerve palsy was also comparable between the two groups (31.8% vs. 18.8%, P=0.469). Operative mortalities developed in 2 patients [0 vs. 2 (12.5%), P=0.171] due to acute respiratory distress syndrome (ARDS). Conclusions: Radical esophagectomy for esophageal squamous cell carcinoma after neoadjuvant chemoradiation therapy with pembrolizumab may not increase the operative risk or reduce the quality of radical dissection including lymphadenectomy. The risk of ARDS after neoadjuvant neoadjuvant chemoradiation therapy with pembrolizumab has to be studied in the further analysis.