Induction immunotherapy plus chemotherapy followed by definitive chemoradiation therapy in locally advanced esophageal squamous cell carcinoma: a propensity-score matched study

Abstract Background For patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), concurrent chemoradiotherapy (CCRT) is the current standard treatment; however, the prognosis remains poor. Immunotherapy combined with chemotherapy has demonstrated improved survival outcomes in advanced ESCC. Nevertheless, there is a lack of reports on the role of induction immunotherapy plus chemotherapy prior to CCRT for unresectable locally advanced ESCC. Therefore, this study aimed to evaluate the efficacy and safety of induction immunotherapy plus chemotherapy followed by definitive chemoradiotherapy in patients with unresectable locally advanced ESCC. Methods This study retrospectively collected clinical data of patients diagnosed with locally advanced ESCC who were treated with radical CCRT between 2017 and 2021 at our institution. The patients were divided into two groups: an induction immunotherapy plus chemotherapy group (induction IC group) or a CCRT group. To assess progression-free survival (PFS) and overall survival (OS), we employed the Kaplan–Meier method after conducting propensity score matching (PSM). Results A total of 132 patients with unresectable locally advanced ESCC were included in this study, with 61 (45.26%) patients in the induction IC group and 71 (54.74%) patients in the CCRT group. With a median follow-up of 37.0 months, median PFS and OS were 25.2 and 39.2 months, respectively. The patients in the induction IC group exhibited a significant improvement in PFS and OS in comparison with those in the CCRT group (median PFS: not reached NR versus 15.9 months, hazard ratio HR 0.526 95%CI 0.325–0.851, P = 0.0077; median OS: NR versus 25.2 months, HR 0.412 95%CI 0.236–0.719, P = 0.0012). After PSM (50 pairs), both PFS and OS remained superior in the induction IC group compared to the CCRT group (HR 0.490 95%CI 0.280–0.858, P = 0.011; HR 0.454 95%CI 0.246–0.837, P = 0.0093), with 2-year PFS rates of 67.6 and 42.0%, and the 2-year OS rates of 74.6 and 52.0%, respectively. Multivariate analysis revealed that lower tumor stage, concurrent chemotherapy using double agents, and induction immunotherapy plus chemotherapy before CCRT were associated with better prognosis. Conclusions Our results showed for the first time that induction immunotherapy plus chemotherapy followed by CCRT for unresectable locally advanced ESCC provided a survival benefit with manageable safety profile. More prospective clinical studies should be warranted.