Abstract
OBJECTIVE: Neoadjuvant chemoradiotherapy (NCRT) combined with surgery has emerged as a crucial therapeutic approach for locally advanced esophageal cancer. However, the effectiveness of pathological complete response (pCR) as a short-term surrogate endpoint remains unclear. This meta-analysis aimed to investigate whether pCR significantly influences the long-term survival of patients with locally advanced esophageal cancer following NCRT combined with surgery. METHODS: A systematic literature search was conducted in February 2024. The inclusion criteria encompassed resectable esophageal cancer cases that had received preoperative chemotherapy, radiation therapy, or chemoradiotherapy as neoadjuvant treatment. Random-effects or fixed-effects model was applied, and heterogeneity was quantified using Higgins' I(2) statistic. RESULTS: Thirty-eight articles were included. The meta-analysis demonstrated that pCR was associated with improved long-term survival following NCRT combined with surgery in patients with esophageal cancer (OS: HR = 0.54, 95%CI 0.52-0.57, DFS: HR = 0.51, 95%CI 0.46-0.57). Furthermore, a subgroup analysis revealed that patients achieving pCR exhibited a greater survival benefit compared to those who did not, when stratified by histology [squamous cell carcinoma or adenocarcinoma] (OS: HR(ESCC)=0.5, 95%CI 0.43-0.59; HR(EAC)=0.35, 95%CI 0.21-0.58, DFS: HR(ESCC)=0.46, 95%CI 0.37-0.56; HR(EAC)=0.46, 95%CI 0.30-0.68). In addition, patients with ESCC had a higher pCR rate, no correlation was found between clinical stage and pCR incidence. And tumor located in upper/middle esophagus was more likely to achieve pCR after NCRT. CONCLUSION: PCR after NCRT was significantly associated with the long-term survival prognosis of esophageal cancer. The findings of this meta-analysis suggest that pCR may serve as a surrogate endpoint for evaluating the survival outcomes of NCRT.