Optimizing neoadjuvant radiotherapy for locally advanced esophageal squamous cell carcinoma: a comprehensive review on the role of concomitant or sequential immune checkpoint inhibitors.

Esophageal squamous cell carcinoma (ESCC) is a prevalent form of esophageal cancer with a poor prognosis despite advances in treatment. Combining immune checkpoint inhibitors (ICIs) with radiotherapy (RT) or chemoradiotherapy (CRT) has shown potential in enhancing treatment efficacy. We conducted a comprehensive review of clinical trials published between 2019 and 2024, sourced from PubMed, Scopus, and Embase databases. Studies included were prospective phase II trials that evaluated the combination of ICIs with neoadjuvant chemoradiotherapy (nCRT) in resectable locally advanced ESCC. Ten trials met the inclusion criteria. The review highlights various approaches in combining ICIs with CRT, including concurrent, induction, and consolidation therapy. Among the included trials, a significant proportion focused on concurrently administering ICIs with CRT, showing promising outcomes with high pathological complete response rates (pCR) and manageable toxicities. However, further research is needed to validate the efficacy of induction and consolidation therapies and determine optimal treatment protocols. The combination of ICIs and nCRT can potentially improve treatment responses and outcomes for patients with locally advanced ESCC. Despite recent encouraging findings, most trials were single-arm with small sample sizes, indicating the need for larger studies with longer follow-ups to assess survival outcomes comprehensively.