Zhang Hai, Li Cui, Lin Jiangbo, Xie Xihao, Peng Fengyuan, Feng Caihou, Che Weibi, Huang Jiawei, Wu Bomeng
Department of Thoracic Surgery, Gaozhou People's Hospital, Gaozhou, China.
Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
Front Med (Lausanne). 2025 Aug 4;12:1608313. doi: 10.3389/fmed.2025.1608313. eCollection 2025.
Esophageal squamous cell carcinoma (ESCC) remains a highly aggressive malignancy with a significant risk of recurrence, even after curative treatment. While neoadjuvant immunochemotherapy (nICT) combined with minimally invasive esophagectomy (MIE) has shown promise in improving outcomes for patients with locally advanced, resectable ESCC, the factors contributing to early postoperative recurrence remain unclear. This study aims to identify high-risk factors for short-term recurrence and develop a predictive model for recurrence in patients with locally advanced, resectable ESCC treated with nICT followed by MIE (McKeown approach).
Patients with locally advanced, resectable ESCC who underwent nICT followed by MIE at Gaozhou People's Hospital between 1 January 2019, and 1 January 2022, were consecutively included in the training set. Patients who received the same treatment at Union Hospital of Fujian Medical University during the same period were included as the validation set. A recurrence prediction model was developed based on these cohorts.
A total of 362 patients treated with nICT were included, including 218 in the training set and 144 in the validation set. Least absolute shrinkage and selection operator regression identified the 10 most significant variables associated with recurrence: smoking history, drinking history, diarrhea, number of lymph nodes dissected, number of lymph node dissection stations, pathological N (pN) stage, pathological TNM stage, tumor regression grade, nerve invasion, and postoperative arrhythmia. Multivariate regression analysis further identified pN+ and nerve invasion as independent high-risk factors for recurrence. The recurrence prediction model demonstrated strong discriminatory ability, with an area under the curve of 0.92 in the training set and 0.91 in the validation set at 3 years postoperatively. Survival analysis showed a statistically significant difference ( < 0.05) in the 3-year overall survival and recurrence-free survival between risk groups. In the low-risk group, postoperative adjuvant therapy did not provide a survival benefit; in the high-risk group, it significantly improved outcomes.
Patients with locally advanced ESCC treated with nICT followed by MIE who have a high pN stage and pathological evidence of nerve invasion may benefit from intensified adjuvant therapy to improve long-term survival.
食管鳞状细胞癌（ESCC）仍然是一种侵袭性很强的恶性肿瘤，即使经过根治性治疗，复发风险依然很高。虽然新辅助免疫化疗（nICT）联合微创食管切除术（MIE）在改善局部晚期、可切除ESCC患者的预后方面显示出前景，但导致术后早期复发的因素仍不清楚。本研究旨在确定局部晚期、可切除ESCC患者经nICT序贯MIE（McKeown术式）治疗后短期复发的高危因素，并建立复发预测模型。
2019年1月1日至2022年1月1日在高州人民医院接受nICT序贯MIE治疗的局部晚期、可切除ESCC患者连续纳入训练集。同期在福建医科大学附属协和医院接受相同治疗的患者纳入验证集。基于这些队列建立复发预测模型。
共纳入362例接受nICT治疗的患者，其中训练集218例，验证集144例。最小绝对收缩和选择算子回归确定了与复发相关的10个最显著变量：吸烟史、饮酒史、腹泻、清扫淋巴结数目、淋巴结清扫站数、病理N（pN）分期、病理TNM分期、肿瘤退缩分级、神经侵犯和术后心律失常。多因素回归分析进一步确定pN+和神经侵犯是复发的独立高危因素。复发预测模型显示出很强的辨别能力，术后3年训练集曲线下面积为0.92，验证集为0.91。生存分析显示，风险组之间3年总生存和无复发生存存在统计学显著差异（<0.05）。在低风险组，术后辅助治疗未带来生存获益；在高风险组，则显著改善了预后。
局部晚期ESCC患者经nICT序贯MIE治疗后，pN分期高且有神经侵犯病理证据者可能从强化辅助治疗中获益，以提高长期生存。
