3466 - Neoadjuvant Therapy Approaches for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Purpose/Objective(s): The standard approach for resectable locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant therapy followed by surgery. However, the optimal neoadjuvant regimen remains uncertain. This study aimed to compare the efficacy of various neoadjuvant treatment strategies in this patient population.

Materials/Methods: A comprehensive search of biomedical databases was performed to identify eligible randomized controlled trials (RCTs) comparing at least two neoadjuvant treatments for resectable locally advanced ESCC. The revised Cochrane risk-of-bias tool (RoB2) was used to assess the risk of bias in individual studies. The outcomes of interest were overall survival (OS) and pathological complete response (pCR) rates. The GRADE approach was employed to appraise the certainty of evidence. A fixed-effects frequentist network meta-analysis was performed, with doublet chemotherapy using platinum-fluorouracil, as the reference group.

Results: Six RCTs including 1,766 patients were identified. Six neoadjuvant regimens were evaluated: triplet chemotherapy (docetaxel-cisplatin-fluorouracil; triplet-DCF), doublet chemotherapy (platinum-fluorouracil (doublet-PF) or platinum-paclitaxel (doublet-PP)), chemoradiation (platinum-fluorouracil (chemoradiation-PF) or platinum-paclitaxel (chemoradiation-PP)), and chemoimmunotherapy (camrelizumab-cisplatin-paclitaxel; Cam-PP). All trials had a low risk of bias. Triplet-DCF ranked the highest in OS (hazard ratio (HR), 0.68; 95% confidence interval (CI), 0.53-0.87; P-score, 0.95), followed by chemoradiation-PF (HR, 0.84; 95% CI, 0.67-1.06; P-score, 0.53), chemoradiation-PP (HR 0.85; 95% CI, 0.68-1.07; P-score, 0.57), and doublet-PP (HR, 0.89; 95% CI, 0.72-1.10; P-score, 0.37). Chemoradiation-PP (odd ratio (OR), 3.71; 95% CI, 1.89-7.29; P-score, 0.15) and chemoradiation-PF (OR, 2.90; 95% CI, 0.96-8.74; P-score, 0.33) were associated with the highest odds of pCR rates, followed by Cam-PP (OR, 2.87; 95% CI, 1.04-7.93; P-score, 0.33), triplet DCF (OR, 2.54; 95% CI, 1.26-5.15; P-score, 0.44), and doublet PP (OR 1.35; 95% CI 0.80-2.28; P-score, 0.79). The certainty of evidence was high for both OS and pCR outcomes.

Conclusion: High-certainty evidence suggests no significant differences in OS and pCR rates among neoadjuvant regimens in resectable locally advanced ESCC compared to doublet-PF, as indicated by overlapping confidence intervals. While chemoradiation achieved the highest pCR rates, triplet-DCF demonstrated the most favorable OS. These findings highlight the complexity of selecting an optimal neoadjuvant strategy and underscore the need for further research to refine personalized treatment approaches.