Frontiers in immunology · 2026
Neoadjuvant chemoradiotherapy versus immunochemotherapy in esophageal squamous cell carcinoma: a propensity-matched analysis of response, survival, lymph node pattern, and immune microenvironment.
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Yehan Zhou, Zhou Xiaoqing, Hu Shangzhi, Yang Qiao, Leng Xuefeng, He Wenwu, Wang Qifeng, Lyu Jiahua, Qing Haomiao, Liu Yang, Yang Hong
Аннотация
OBJECTIVE: To compare efficacy, survival and tumor immune microenvironment between neoadjuvant chemoradiotherapy (NCRT) and neoadjuvant immunochemotherapy (NICT) in patients with esophageal squamous cell carcinoma (ESCC) to guide individualized treatment.
METHODS: A total of 346 locally advanced ESCC patients after 1:1 propensity score matching were retrospectively analyzed. Pathological, radiological and multiplex immunofluorescence assessments were performed, and survival outcomes were evaluated.
RESULTS: NCRT resulted in significantly greater tumor volume reduction (22.09 vs. 15.37 mm³), lower residual primary tumor ratio (14.10% vs. 32.23%), higher tumor downstaging and pathological complete response (pCR) rates (all p < 0.05). NCRT showed more prominent lymph node regression adjacent to the primary tumor than in peripheral nodes. Overall survival (OS) and recurrence-free survival (RFS) were comparable between groups. Among pCR patients, NICT achieved significantly better OS (p = 0.0051) and RFS (p = 0.018), while NCRT was associated with superior RFS in non-pCR patients (p = 0.0099). In the NICT group, high PD-L1 expression and low tumor burden tended to correlate with pCR. Immune microenvironment analysis revealed fewer immunosuppressive T cells and immune-evasive tumor cells in the NICT group.
CONCLUSION: NCRT presents superior local tumor regression, while NICT benefits pCR patients by optimizing the immune microenvironment. High PD-L1 expression and low tumor burden favor NICT. These findings support individualized neoadjuvant strategy selection for ESCC.
METHODS: A total of 346 locally advanced ESCC patients after 1:1 propensity score matching were retrospectively analyzed. Pathological, radiological and multiplex immunofluorescence assessments were performed, and survival outcomes were evaluated.
RESULTS: NCRT resulted in significantly greater tumor volume reduction (22.09 vs. 15.37 mm³), lower residual primary tumor ratio (14.10% vs. 32.23%), higher tumor downstaging and pathological complete response (pCR) rates (all p < 0.05). NCRT showed more prominent lymph node regression adjacent to the primary tumor than in peripheral nodes. Overall survival (OS) and recurrence-free survival (RFS) were comparable between groups. Among pCR patients, NICT achieved significantly better OS (p = 0.0051) and RFS (p = 0.018), while NCRT was associated with superior RFS in non-pCR patients (p = 0.0099). In the NICT group, high PD-L1 expression and low tumor burden tended to correlate with pCR. Immune microenvironment analysis revealed fewer immunosuppressive T cells and immune-evasive tumor cells in the NICT group.
CONCLUSION: NCRT presents superior local tumor regression, while NICT benefits pCR patients by optimizing the immune microenvironment. High PD-L1 expression and low tumor burden favor NICT. These findings support individualized neoadjuvant strategy selection for ESCC.