A Randomized Controlled Phase 3 Trial of Oral Prednisolone Administration Versus Local Triamcinolone Injection Therapy for Esophageal Stricture Prevention After Extensive Endoscopic Submucosal Dissection ( <scp>JCOG1217</scp> )

OBJECTIVES: Endoscopic local triamcinolone injection is a standard therapy for esophageal stricture (ES) prevention after extensive endoscopic submucosal dissection (ESD); however, oral prednisolone administration is a promising alternative. This trial aimed to investigate the superiority of oral prednisolone administration to local triamcinolone injection for ES prevention after extensive ESD. METHODS: This phase 3, open-label, multicenter, randomized controlled trial enrolled patients with extensive superficial esophageal squamous cell carcinoma. The primary endpoint was stricture-free survival (SFS). Secondary endpoints were the number of endoscopic balloon dilations (EBDs) for 12 weeks after ESD, dysphagia score ≤ 1 at 12 weeks after ESD, and adverse events (AEs). RESULTS: A total of 281 patients from 45 institutions were enrolled. The 12-week SFS rates were 88.5% (95% confidence interval [CI]: 81.6-92.9) and 94.8% (95% CI: 89.4-97.5) in the triamcinolone and prednisolone arms, respectively (hazard ratio 0.672, 90% CI [0.361-1.250], p = 0.14). Thirty-eight and 26 EBDs were performed for 14 and 10 patients, respectively, in the triamcinolone and prednisolone arms within 12 weeks after ESD. In the triamcinolone and prednisolone arms, 73.8% (95% CI: 65.7-80.8) and 80.7% (95% CI: 73.2-86.9) of patients, respectively, had dysphagia scores ≤ 1 at 12 weeks after ESD (p = 0.20). Grade 3/4 AEs occurred in 12 (8.7%) and 9 patients (6.7%) in the triamcinolone and prednisolone arms, respectively. CONCLUSIONS: While oral prednisolone administration and local triamcinolone injection demonstrated comparable outcomes, oral prednisolone did not demonstrate superiority for ES prevention after extensive esophageal ESD.