Research trends in neoadjuvant therapy for esophageal cancer: a bibliometric and meta-analysis.

Background: Neoadjuvant treatment followed by radical surgery has become the standard treatment approach for locally advanced esophageal cancer. We aimed to explore the development trends, research hotspots, and differences among treatment regimens in this field using bibliometric analysis and meta-analysis. Methods: Literature on neoadjuvant therapy for esophageal cancer was retrieved from PubMed, Embase, Cochrane Library, and Web of Science. Bibliometric analysis and visualization were conducted on publications since 2000 from Web of Science Core Collection (WoSCC) using CiteSpace, VOSviewer, and the bibliometrix package in RStudio. A meta-analysis of phase III randomized controlled trials (RCTs) involving different treatment regimens was performed using Stata/MP, based on studies screened from all four databases. Results: A total of 1,324 and 27 studies were included in the bibliometric analysis and meta-analysis, respectively. Overall, there was an increasing trend in the volume of publications in this field. The United States and the Karolinska Institute emerged as the leading country and institution in terms of publication volume. The most frequently cited journals and authors were Annals of Surgery and van Hagen P, respectively. Research hotspots have primarily focused on neoadjuvant chemotherapy (NCT) and chemoradiotherapy (NCRT), with a recent shift toward neoadjuvant immunotherapy (NIT). The pooled complete pathological response (pCR) rates were 0.08 for NCT, 0.29 for NCRT, 0.22 for neoadjuvant chemoimmunotherapy (NCIT), and 0.27 for NCRT combined with targeted therapy (NCRT+NTT). The pooled rates of tumor regression grade 1 (TRG1) were 0.09, 0.25, 0.30, and 0.37, respectively. The R0 resection rates were 0.87, 0.96, 0.99, and 0.96, while the incidence of grade ≥3 treatment-related adverse events (TRAEs) was 0.37, 0.66, 0.25, and 0.69, respectively. Conclusions: Neoadjuvant therapy for esophageal cancer has evolved significantly over the past decades. Recently, NIT has emerged as a key area of research interest. However, its clinical efficacy and safety require validation through long-term follow-up data from future phase III RCTs.