Retrospective analysis of the optimal timing of immunotherapy in patients with advanced esophageal squamous cell carcinoma: a window of opportunity

This study aimed to define the optimal 'treatment window' for ICI therapy to maximize survival. In this retrospective cohort study, 149 advanced ESCC patients treated with ICIs were analyzed. Progression-free-survival (PFS) and overall-survival (OS) were assessed using Kaplan-Meier methods and Cox models. The median duration of ICI therapy was 21.0 months, with a median follow-up of 34.6 months. Treatment ≥12 months emerged as critical, significantly improving median PFS (14.0 m vs. 9.1, P = 0.006) and median OS (20.5 m vs. 16.8 m, P = 0.022). The survival benefit increased with longer durations (e.g. ≥24 months). For patients with stable disease (SD), maintaining therapy for ≥12 months was crucial, significantly improving OS (19.2 m vs. 15.5 m, P < 0.001), particularly with second-line or later ICI therapy. Subgroup analyses confirmed the robustness of the 12-month threshold, showing significant PFS and OS benefits in patients receiving second-line or later therapy (PFS: 13.4 m vs. 8.6 m, P = 0.031; OS: 20.5 m vs. 16.6 m, P = 0.015) and combination ICI therapy (PFS: 14.1 m vs. 8.3 m, P = 0.004; OS: 20.1 m vs. 16.8 m, P = 0.041). This real-world study identifies a 12-month minimum ICI treatment window for advanced ESCC, with optimal benefit extending to 24 months and beyond, particularly crucial for SD or later-line/combination therapy cases.