The Long-term Outcomes of Borderline Resectable T3 in Locally Advanced Esophageal Squamous Cell Carcinoma Treated With Neoadjuvant Triplet Chemotherapy

This study compared the clinical characteristics and outcomes between patients with resectable clinical T3 (cT3r) and borderline resectable clinical T3 (cT3br) esophageal squamous cell carcinoma (ESCC) who underwent neoadjuvant triplet chemotherapy. The study cohort comprised patients treated at our institution between January 2010 and November 2020 who underwent neoadjuvant chemotherapy using a triplet regimen - either DCF or DCS - followed by esophagectomy for cT3. Eligible patients were divided into cT3r and cT3br groups. A total of 127 patients with cT3 ESCC were included, comprising 101 in the cT3r group and 26 in the cT3br group. The numbers of patients with complete response, partial response, stable disease, and progressive disease were significantly different between the cT3r and cT3br groups (4.9%, 52.5%, 8.9% and 3.0% vs. 3.9%, 42.3%, 19.2% and 23.1%, respectively; p=0.003). Anastomotic leakage (≥Clavien-Dindo grade III) occurred significantly more frequently in the cT3br group than in the cT3r group (38.5% vs. 9.9%, respectively; p=0.001). Surgical radicality of R0, R1, and R2 was significantly different between the cT3r and cT3br groups (93.0%, 4.0% and 3.0% vs. 57.6%, 7.7% and 34.7%, respectively; p<0.001). In survival analysis, the three-year recurrence-free and overall survival rates were significant different between the groups (53.1% vs. 24.9%; p<0.001, 59.8% vs. 32.6%, respectively; p<0.001). Multivariate analysis identified cT3br status (p=0.016) and poor histological response ≤1a (p<0.001) as independent prognostic factors for overall survival. cT3br and poorer histological response were identified as prognostic factors of overall survival in this retrospective cohort study. Neoadjuvant chemotherapy alone may be insufficient to achieve curative outcomes in cT3br cases. For patients who do not respond adequately to initial chemotherapy, the addition of preoperative chemoradiotherapy may be necessary to enhance local tumor control and improve long-term survival.