Efficacy and safety of endoscopic resection followed by chemoradiotherapy with S-1 plus cisplatin for esophageal cancer.

BACKGROUND: Chemoradiotherapy (CRT) with 5-fluorouracil plus cisplatin is commonly used as additional treatment after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC); however, metastatic recurrence remains a concern. S-1 is an oral fluoropyrimidine that has shown efficacy in combination with cisplatin and radiotherapy. This single-center, single-arm, exploratory phase II study evaluated the efficacy and safety of ER followed by CRT using S-1 plus cisplatin for superficial ESCC (UMIN000014684). METHODS: Patients with ESCC diagnosed with stage pT1a-MM or pT1b-SM disease or lymphovascular invasion after ER were enrolled. CRT consisted of two cycles of S-1 administered twice daily on days 1 to 14 and cisplatin (70 mg/m²) on day 1 every 4 weeks, in conjunction with radiotherapy (40.0-41.4 Gy). The primary endpoint was 3-year overall survival (OS). Progression-free survival and adverse events were also examined. RESULTS: Thirty-eight patients underwent CRT with S-1 plus cisplatin. The 3-year OS and progression-free survival rates were 94.7% (90% confidence interval [CI], 84.1-98.3%) and 92.1% (90% CI, 80.8-96.9%), respectively. The lower limit of the 90% CI for 3-year OS exceeded the predefined threshold. Grade ≥ 3 adverse events occurred in 55% of patients, with no cases of febrile neutropenia. Metastatic recurrence was observed in two patients (5%). CONCLUSIONS: ER followed by CRT with S-1 plus cisplatin showed favorable survival outcomes with a manageable toxicity profile in patients with superficial ESCC requiring additional treatment, although careful monitoring of adverse events and further validation is warranted.