Efficacy and safety of neoadjuvant chemotherapy with immunotherapy versus chemotherapy alone in esophageal squamous cell carcinoma: a meta-analysis based on randomized controlled trials

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Abstract

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) remains one of the most aggressive and lethal cancers, with high incidence and mortality rates in East Asia. Neoadjuvant chemotherapy (NC) has traditionally been the standard approach for improving resectability in ESCC, but its limited efficacy in achieving complete pathological responses and enhancing survival has driven interest in combining it with immune checkpoint inhibitors (ICIs), resulting in neoadjuvant chemoimmunotherapy (NIC). Based on randomized controlled trials (RCTs), this meta-analysis compares the risks and clinical benefits of NIC versus NC in resectable ESCC patients. METHODS: This meta-analysis systematically reviewed data from randomized controlled trials (RCTs) comparing NIC and NC in the treatment of resectable ESCC. Primary outcomes included pathological complete response (pCR) and major pathological response (MPR), while secondary outcomes focused on overall survival (OS), event-free survival(EFS), surgery rate, microscopically margin-negative resection(R0 resection), Intraoperative and hospitalization indicators, T Staging, Response evaluation criteria in solid tumors(RECIST), and adverse events (AEs). RESULTS: Six high-quality RCTs (1070 patients) were included. NIC significantly improved major pathological response(MPR) (42.8% vs. 22.2%, Odds Ratio(OR) = 2.40, p = 0.0007) and pathological complete response(pCR) (22.2% vs. 8.0%, OR = 3.53, p < 0.00001). NIC was also associated with borderline statistically significant improvements in overall survival (OS) (HR = 0.57, p = 0.05) and R0 resection rate (OR = 2.56, p = 0.05). In addition, NIC enhanced surgical rate (OR = 1.57, p = 0.02), lymph node resection (Mean Difference (MD) = 1.76, P = 0.008), and NIC with a longer interval to surgery (MD = 4.73, p = 0.003, I2 = 95%), although this pooled estimate is less reliable because of considerable heterogeneity. However, immune-related adverse events (iRAEs) were higher in NIC (23.21% vs. 1.16%, p < 0.00001), though severe AEs were similar. CONCLUSIONS: NIC significantly improves pathological response and other perioperative benefits (e.g., surgical rate and lymph node resection) in resectable ESCC compared with NC, with a trend toward improved survival, despite a higher incidence of irAEs. Further studies are needed to optimize treatment protocols and clarify the long-term impact of immune-related toxicities.

Abstract as published, via PubMed.