Definitive Chemoradiotherapy Following Preoperative Induction Chemotherapy in Esophageal Squamous Cell Carcinoma: Prognostic Impact of Response

Background/Aim: The role of induction chemotherapy (IC) before definitive chemoradiotherapy (CRT) in esophageal squamous cell carcinoma (ESCC) remains controversial, and outcomes among patients who begin chemotherapy with preoperative intent but eventually transition to definitive CRT are not well characterized. This study aimed to describe outcomes of definitive CRT with and without prior IC and to explore the prognostic value of chemotherapy response. Patients and Methods: Patients with clinical stage II-IVa ESCC treated with definitive radiotherapy were retrospectively reviewed at a single center between 2014 and 2022. Of them, 54 patients treated with definitive CRT were analyzed: 31 received preoperative IC before transitioning to definitive CRT, and 23 received upfront definitive CRT (non-IC group). The IC group was clinically heterogeneous, having transitioned to CRT for varied reasons (persistent unresectability in 18, patient preference in 9, comorbidity or perioperative risk in 4). Median follow-up was 22.5 months. Results: Two-year overall survival (OS), progression-free survival (PFS), and locoregional control did not differ significantly between the IC and non-IC groups (OS: 65.4% vs. 59.4%, p=0.559; PFS: 33.7% vs. 52.0%, p=0.465; locoregional control: 53.2% vs. 69.2%, p=0.402). Within the IC group, a response (partial/complete) to chemotherapy was associated with more favorable OS (p=0.008) and PFS (p=0.010); the association with locoregional control was not significant (p=0.059). Grade ≥3 late adverse events were persistent in the IC group, and there were four treatment-related deaths (7%). Conclusion: Induction chemotherapy before definitive CRT was not associated with improved survival in this selected cohort of ESCC. Response to induction chemotherapy was associated with more favorable OS and PFS and may have prognostic relevance, although it does not justify a response-adapted treatment strategy.