Induction chemotherapy followed by definitive chemoradiation in patients with inoperable esophageal squamous cell carcinoma: a multicenter retrospective study

Background: Esophageal squamous cell carcinoma (ESCC) remains a global health challenge, characterized by significant geographic variations in incidence, risk factors, and treatment paradigms. While definitive chemoradiotherapy (CRT) is the cornerstone of therapy for inoperable locally advanced disease, the role of induction chemotherapy followed by CRT (CT-CRT) remains underexplored, particularly in Western populations. This study aimed to assess the survival outcomes of CRT and CT-CRT in a multicenter cohort with inoperable locally advanced ESCC. Methods: This retrospective multicenter cohort study included 92 patients with inoperable stage II-IVA ESCC treated with CRT or CT-CRT between May 2015 and January 2024. Disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS), response rates, and recurrence patterns were assessed and compared between CRT and CT-CRT groups. Results: The median age was 59 years, with a balanced gender distribution (52.2% male). The CT-CRT group exhibited significantly improved DMFS compared to CRT alone (HR: 0.363, 95% CI 0.154–0.857; p = 0.016). DFS and OS were similar in the CT-CRT group and CRT group, although there was a trend towards improved DFS and OS with CT-CRT (DFS: 16.9 vs. 11.4 months, p = 0.330; OS: 38.6 vs. 18.8 months, p = 0.209). In subgroup analysis, CT-CRT was associated with improved survival outcomes compared to CRT alone in advanced T stage (cT3–cT4) and TNM stage (III–IV). Conclusion: Induction chemotherapy followed by CRT showed significantly improved DMFS and a trend towards improved DFS and OS in inoperable ESCC, particularly prominent in patients with more advanced T (T3–T4) or TNM (III–IV) stages.