Clinicopathological Factors Influencing Survival After Trimodality Treatment in Non-Metastatic Esophageal Cancer: A...

Background: In locally advanced squamous cell esophageal cancer, concurrent chemoradiotherapy (CRT) is the standard of care, as it especially improves local control and overall survival compared to radiotherapy alone. In contrast, treatment strategies for esophageal adenocarcinoma often parallel those used in gastric cancer, particularly regarding systemic therapy. Objectives: This study aimed to evaluate the clinicopathological factors affecting event-free survival (EFS) and overall survival (OS) following trimodality treatment in patients with non-metastatic esophageal cancer. Methods: A total of 155 patients diagnosed with esophageal cancer between March 2019 and November 2025 were retrospectively analyzed. Response to concurrent chemoradiotherapy was assessed via thoracic magnetic resonance imaging and endoscopic biopsy. Results: Clinicopathological analysis showed that male sex, the presence of lymphovascular invasion, adenocarcinoma histology, poor pathological response and advanced-stage tumors were significantly associated with worse EFS (all p < 0.001). In multivariate analysis, stage IVa disease was identified as an independent predictor of both mortality and relapse, with an approximately five-fold increased risk of death (p = 0.028) and relapse (p = 0.019). Patients with squamous cell carcinoma had a longer median EFS compared to those with adenocarcinoma (18 vs. 8.4 months, respectively). The 3- and 5-year OS rates were 59.2% and 56% in patients with squamous cell carcinoma, compared with 40% and 26% in those with adenocarcinoma, respectively. Conclusions: Survival outcomes were more favorable in patients with squamous cell histology and those diagnosed at an early stage. Active surveillance may be considered in selected patients with a complete clinical response to avoid the perioperative mortality associated with surgery.