Efficacy and safety of neoadjuvant chemoimmunotherapy versus neoadjuvant chemoradiotherapy in locally advanced resectable esophageal squamous cell carcinoma.

OBJECTIVE: To compare the efficacy and safety of neoadjuvant chemoradiotherapy (NCRT) versus chemoimmunotherapy (NCIT) in resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC). METHODS: Patients with LA-ESCC who underwent NCIT or NCRT were retrospectively enrolled between November 2017 and April 2024. Propensity score matching (PSM) was applied to balance the baseline characteristics. Treatment response, survival outcomes, and safety were compared between groups. RESULTS: 501 patients were enrolled, with 204 in the NCRT group and 297 in the NCIT group. After PSM, 148 matched pairs were analyzed. The NCRT group had a superior objective response rate (ORR) (68.2% vs. 54.7%, P = 0.023), pathological complete response (pCR) rate (46.6% vs. 20.9%, P < 0.001), tumor regression grade (TRG) distribution (P < 0.001), 2-year disease-free survival (DFS) (77.4% vs. 66.0%, P = 0.007) and overall survival (OS) rates (93.7% vs. 81.5%, P < 0.001) compared with NCIT group. The survival benefit was confined to patients who did not achieve pCR (both P < 0.05). Deeper tumor regression was strongly associated with improved DFS and OS (P for trend < 0.001). The incidence of postoperative complications and adverse events was comparable between groups. However, grade ≥ 3 hematologic toxicity was significantly higher with NCRT (36.5% vs. 6.8%, P < 0.001). CONCLUSION: NCRT demonstrated superior pCR rates and mid-term survival outcomes to NCIT in resectable LA-ESCC, likely related to deeper tumor regression. TRG scores after neoadjuvant therapy predict graded survival benefit, provide more refined prognostic stratification, and complement pCR. Although postoperative complication rates were comparable, NCRT induced higher grade ≥ 3 hematologic toxicity, necessitating vigilant monitoring.