Optimal Treatment Strategies for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Real-World Triple Cohort Analysis Using Propensity Score Matching

Dan Han,1,2 Jing Tian,3 Junfeng Zhao,2 Shaoyu Hao4,5 1Department of Radiation Oncology, Shandong University Cancer Center, Jinan, Shandong, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Department of Radiation Oncology, Jinan Zhangqiu District People’s Hospital, Jinan, Shandong, People’s Republic of China; 4Department of Thoracic Surgery, Shandong University Cancer Center, Jinan, Shandong, People’s Republic of China; 5Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Shaoyu Hao, Department of Thoracic Surgery, Shandong University Cancer Center, Jinan, Shandong, China; Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China, Tel +86 13188870730, Email hshaoyu1985@126.comPurpose: This study aims to identify the most effective treatment approach and compares the survival rates, along with complications, in patients with locally resectable esophageal squamous cell carcinoma (ESCC) who were treated with one of the three treatment patterns: neoadjuvant chemotherapy followed by surgery (NCT+S), neoadjuvant chemoradiotherapy followed by surgery (NCRT+S), or surgery followed by chemoradiotherapy (S+CRT).Methods: We conducted a retrospective analysis of the medical records of ESCC patients who received one of these treatments between March 2015 and March 2022. This analysis aimed to identify differences in long-term survival, pathological responses, and complications across the three treatment groups. To address potential confounding factors, propensity score matching (PSM) and Cox proportional hazards models were utilized.Results: This study included a cohort of 715 patients: 197 in the NCT+S group, 188 in the NCRT+S group, and 330 in the S+CRT group, all meeting the selection criteria. After PSM, the median disease-free survival (DFS) time was 38.9 months, 25.6 months, and 15.3 months for NCRT+S, NCT+S, and S+CRT groups, respectively. There were statistically significant differences in the 5-year DFS and 5-year OS among the three groups (P=0.04 and P=0.02, post-matching, respectively). Notably, neoadjuvant therapy showed a correlation with increased postoperative anastomotic leakage rates (17.5% in NCRT+S, 10% in NCT+S, and 5% in S+CRT; P=0.03, post-matching), regardless of the PSM adjustment.Conclusion: The findings indicate that neoadjuvant therapy before surgery offers a significant survival advantage over postoperative adjuvant therapy for patients with locally advanced resectable ESCC. Despite similar safety profiles, neoadjuvant therapy appears to be associated with a higher incidence of anastomotic leakage after surgery.Keywords: neoadjuvant therapy, esophageal squamous cell carcinoma, postoperative adjuvant therapy, prognosis