e16068 Background: Neoadjuvant chemoradiotherapy (CRT) is the current standard for resectable esophageal squamous cell carcinoma (ESCC), yet the role of immune checkpoint inhibitors (ICI) remains unclear. We performed a component network meta-analysis (CNMA) comparing CRT, ICI plus chemotherapy, and chemotherapy alone. Methods: Phase II–III trials with pathological or safety outcomes through January 2026 were included. Treatment components - CRT and ICI plus chemotherapy- were analyzed using frequentist random-effects CNMA with chemotherapy alone as a reference. Outcomes included pathological complete response (pCR), major pathological response (MPR), R0 resection rate, and grade ≥3 adverse events (AEs). Results: Nineteen studies (n = 4,502) contributed to a connected network comparing chemoradiotherapy (CRT), ICI plus chemotherapy, and chemotherapy alone. Compared with chemotherapy alone, CRT significantly improved pathologic complete response (pCR; OR 6.53, 95% CI 4.70–9.08) and major pathologic response (MPR; OR 3.37, 95% CI 2.39–4.76), while ICI plus chemotherapy also demonstrated significant benefit for pCR (OR 3.96, 95% CI 3.05–5.15) and MPR (OR 2.51, 95% CI 1.94–3.26). R0 resection rates were significantly higher with ICI plus chemotherapy compared with chemotherapy alone (OR 1.88, 95% CI 1.08–3.26). Grade ≥3 adverse events were higher with chemoradiotherapy (OR 2.32, 95% CI 1.10–4.88) but not with ICI plus chemotherapy (OR 1.38, 95% CI 0.81–2.34). Between-study heterogeneity was moderate (I² range, 22%–67%). Conclusions: Both CRT and ICI plus chemotherapy significantly improve pathological response compared with chemotherapy alone in resectable ESCC. Although CRT achieves the greatest gains in pCR and MPR, ICI plus chemotherapy improves R0 resection and does not significantly increase grade ≥3 adverse events, supporting its favorable benefit-risk profile and emerging role as an alternative neoadjuvant strategy. Pathological and safety outcomes of chemoradiotherapy and ici plus chemotherapy. Outcome Treatment Group Odds Ratio (95% CI) P-value pCR CRT 6.53 (4.70–9.08) <0.001 pCR ICI+Chemo 3.96 (3.05–5.15) <0.001 MPR CRT 3.37 (2.39–4.76) <0.001 MPR ICI+Chemo 2.51 (1.94–3.26) <0.001 R0 Rate CRT 1.76 (0.82–3.76) 0.144 R0 Rate ICI+Chemo 1.88 (1.08–3.26) 0.025 G≥3 AEs CRT 2.32 (1.10–4.88) 0.027 G≥3 AEs ICI+Chemo 1.38 (0.81–2.34) 0.235 Abbreviations: pCR = pathological complete response; MPR = major pathological response; CRT = chemoradiotherapy; ICI = immune checkpoint inhibitor; AEs = adverse events.
Anwar et al. (Thu,) studied this question.