# Three-Year Outcomes of Neoadjuvant Chemoimmunotherapy vs. Neoadjuvant Chemoradiotherapy in Resectable Esophageal Cancer: A Multicenter Retrospective Study

## TL;DR

A study found that neoadjuvant chemoimmunotherapy improves long-term survival for resectable esophageal cancer compared to chemoradiotherapy, though chemoradiotherapy may work better for certain subgroups.

## Contribution

This study provides evidence on the long-term efficacy and safety of neoadjuvant chemoimmunotherapy versus chemoradiotherapy in esophageal cancer patients.

## Key findings

- Neoadjuvant chemoimmunotherapy improved 3-year overall survival and disease-free survival compared to chemoradiotherapy.
- Chemoradiotherapy showed higher objective response rates and pathologic complete response in matched cohorts.
- Subgroup analysis suggested chemoradiotherapy may benefit node-positive or non-cT4 stage patients more.

## Abstract

Evidence regarding neoadjuvant chemoimmunotherapy (nCIT) or neoadjuvant chemoradiotherapy (nCRT) for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) remains controversial. This study (n = 225) investigated the long-term efficacy and safety of nCIT versus nCRT in patients with LA-ESCC. The results suggest that nCIT can improve the long-term survival of patients with resectable esophageal cancer, whereas nCRT may provide greater benefits in patients with node-positive (N+) or non-cT4-stage disease. This study demonstrates the clinical efficacy and safety of nCIT in patients with LA-ESCC.

Background: Patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) have poor prognosis after surgery. Neoadjuvant chemoimmunotherapy (nCIT) and neoadjuvant chemoradiotherapy (nCRT) may improve outcomes, but their long-term efficacy remains unclear. Methods: This multicenter study analyzed LA-ESCC patients from three Chinese hospitals (2015–2024) who received nCIT or nCRT followed by surgery. Primary endpoint was 3-year overall survival (OS); secondary endpoints included objective response rate (ORR), pathologic complete response (pCR), disease-free survival (DFS), and adverse events. Propensity score matching balanced baseline characteristics. Results: Among 225 patients (87 nCRT, 138 nCIT), matched cohorts (87 per group) showed that nCRT had higher ORR (85.06% vs. 45.98%), T/N downstaging rates (78.16% vs. 58.62%; 85.06% vs. 45.98%), and pCR (37.90% vs. 14.90%) (all p < 0.01). After median follow-up (nCIT: 44.5 months; nCRT: 35.1 months), nCIT improved 3-year OS (75.90% vs. 55.60%) and DFS (66.40% vs. 47.30%) (p < 0.05). Subgroup analysis favored nCRT in N+ or non-cT4 disease. Clinical N stage independently predicted survival. Conclusion: nCIT demonstrates superior survival benefits in LA-ESCC, while nCRT may be more effective for N+ or non-cT4 patients. Further randomized trials are warranted.